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Keywords = calcium ion-selective

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16 pages, 3178 KiB  
Article
Engineering Ion Affinity of Zr-MOF Hybrid PDMS Membranes for the Selective Separation of Na+/Ca2+
by Ahmed S. Abou-Elyazed, Xiaolin Li and Jing Meng
Molecules 2024, 29(22), 5297; https://doi.org/10.3390/molecules29225297 - 9 Nov 2024
Viewed by 683
Abstract
Ion-selective separation, especially Na+/Ca2+ separation, is of significant importance in the realms of biomimetic research and the fabrication of biomimetic devices, underscoring the pivotal role that sodium and calcium ions play in cellular metabolism. However, the analogous ionic radii and [...] Read more.
Ion-selective separation, especially Na+/Ca2+ separation, is of significant importance in the realms of biomimetic research and the fabrication of biomimetic devices, underscoring the pivotal role that sodium and calcium ions play in cellular metabolism. However, the analogous ionic radii and charge densities shared by sodium and calcium ions significantly impede their effective discrimination, presenting formidable challenges for the precise engineering of ion separation materials, such as separation membranes. In this study, a polydimethylsiloxane (PDMS) separation membrane hybridized with zirconium-based metal–organic frameworks (UiO-66, UiO-66-NO2 and UiO-66-NH2) was constructed. Through the meticulous design of the MOF functional groups, the material’s affinity for specific ions was modulated, thereby achieving efficient Na+/Ca2+ separation. Notably, the PDMS integrated with amino-modified Zr-MOF exhibited an efficacious selective separation of Na+ and Ca2+ ions. The interaction between the amino group of UiO-66-NH2 and Ca2+ gave rise to the observed superior selectivity toward Ca2+ cations and enhanced separation efficiencies of up to 64% compared to pristine PDMS for UiO-66-NH2-embedded membranes. Full article
(This article belongs to the Section Organometallic Chemistry)
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<p>XRD patterns of different Zr-MOF@PDMS membranes (<b>a</b>) and SEM images of the membrane surface and cross-section morphologies (<b>b</b>–<b>d</b>).</p>
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<p><span class="html-italic">I–V</span> curves of Zr-MOFs@PDMS membranes and the separation ratio (insert tables) (thickness: 600 ± 0.01 μm, pH = 7.42).</p>
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<p>(<b>a</b>) Hydrated ionic diameter (<span class="html-italic">D</span><sub>h</sub>), ionic diameter (<span class="html-italic">D</span><sub>i</sub>), and hydration-free energy (<span class="html-italic">ΔG</span>) f different metal ions; (<b>b</b>–<b>d</b>) N<sub>2</sub> sorption isotherm of different Zr-MOFs, and pore size distribution of Zr-MOFs (inset figures).</p>
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<p>XRD patterns of different Zr-MOFs after immersing in deionized water, 1 mol L<sup>−1</sup> NaCl, 1 mol L<sup>−1</sup> KCl, and 1 mol L<sup>−1</sup> CaCl<sub>2</sub> solutions for 72 h, (<b>a</b>–<b>c</b>) and transport activation energies of Na<sup>+</sup> and Ca<sup>2+</sup> ions in Zr-MOF-0.05@PDMS and PDMS membranes (<b>d</b>).</p>
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<p>XRD patterns of the three Zr-MOF-0.05@PDMS after immersing in a saline solution for ten days.</p>
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<p>The concentration of Na<sup>+</sup> and Ca<sup>2+</sup> in the receiving solution at different times: (<b>a</b>) PDMS, (<b>b</b>) UiO-66-0.05@PDMS, (<b>c</b>) UiO-66-NO<sub>2</sub>-0.05@PDMS and (<b>d</b>) UiO-66-NH<sub>2</sub>-0.05@PDMS membranes.</p>
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<p>The plots of <span class="html-italic">ln</span> ((<span class="html-italic">C</span><sub>0</sub>−2<span class="html-italic">C</span><sub>t</sub>)/<span class="html-italic">C</span><sub>0</sub>) vs. time. (feed solution: 1.0 mol L<sup>−1</sup> NaCl and 1.0 mol L<sup>−1</sup> CaCl<sub>2</sub>; receiving solution: deionized water, membrane: 600 ± 0.01 μm, (<b>a</b>) PDMS, (<b>b</b>) UiO-66-0.05@PDMS, (<b>c</b>) UiO-66-NO<sub>2</sub>-0.05@PDMS and (<b>d</b>) UiO-66-NH<sub>2</sub>-0.05@PDMS membranes; pH = 7.42).</p>
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<p>Schematic procedure for the synthesis of Zr-MOF@PDMS membranes.</p>
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<p>The photograph of the setup for ion conductivity (<b>a</b>) and schematic diagram of the test of ion separation (<b>b</b>).</p>
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24 pages, 5122 KiB  
Article
Selective Leaching of Lithium and Beyond: Sustainable Eggshell-Mediated Recovery from Spent Li-Ion Batteries
by Hossein Shalchian, Maryam Khalili, Alireza Kiani-Rashid, Behzad Nateq and Francesco Vegliò
Minerals 2024, 14(11), 1120; https://doi.org/10.3390/min14111120 - 4 Nov 2024
Viewed by 451
Abstract
This study introduces an innovative strategy for the selective leaching of lithium from spent Li-ion batteries. Based on thermodynamic assessments and exploiting waste eggshells as a source of calcium carbonate, an impressive 38% of lithium was dissolved selectively through mechanical milling and water [...] Read more.
This study introduces an innovative strategy for the selective leaching of lithium from spent Li-ion batteries. Based on thermodynamic assessments and exploiting waste eggshells as a source of calcium carbonate, an impressive 38% of lithium was dissolved selectively through mechanical milling and water leaching, outperforming conventional thermochemical methods. Afterwards, a hydrogen peroxide-assisted sulfuric acid leaching was also implemented to solubilize targeted elements (Mn, Co, Ni, and Li), with an exceptional 99% efficiency in Mn removal from the leachate using potassium permanganate and a pH range of 1.5 to 3.5. Selective separations of Co and Ni were then facilitated utilizing CYANEX 272 and n-heptane. This comprehensive study presents a promising and sustainable avenue for the effective recovery of Li and associated co-elements from spent lithium batteries. Full article
(This article belongs to the Special Issue Recycling of Mining and Solid Wastes)
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<p>The sequence of stages followed in this study.</p>
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<p>Equilibrium composition between 2 moles of LiCoO<sub>2</sub> and 1 mole of calcium carbonate versus temperature predicted by HSC Chemistry<sup>®</sup> 10 (ver. 10.3): (<b>a</b>) equilibrium amounts of possible products, (<b>b</b>) lithium distribution between different components, (<b>c</b>) cobalt distribution between different components, (<b>d</b>) oxygen distribution between different components, (<b>e</b>) calcium distribution between different components, (<b>f</b>) carbon distribution between different components.</p>
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<p>Equilibrium composition between 2 moles of LiMn<sub>2</sub>O<sub>4</sub> and 1 mole of calcium carbonate versus temperature, predicted by HSC Chemistry<sup>®</sup> 10 (ver. 10.3): (<b>a</b>) equilibrium amounts of possible products, (<b>b</b>) lithium distribution between different components, (<b>c</b>) manganese distribution between different components, (<b>d</b>) oxygen distribution between different components, (<b>e</b>) calcium distribution between different components, (<b>f</b>) carbon distribution between different components.</p>
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<p>XRD patterns of the samples milled at different durations (other milling parameters: cathode-to-eggshell weight ratio of 2, BPR of 40, rotational speed of 320 rpm).</p>
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<p>Results of neutral leaching for selective lithium recovery in distinct scenarios: (<b>a</b>) samples milled at different milling durations and a constant cathode-to-eggshell weight ratio of 2, (<b>b</b>) samples milled for 8 h with different cathode-to-eggshell weight ratios, (<b>c</b>) samples milled with magnesium carbonate at different durations and a constant cathode-to-magnesium carbonate weight ratio of 2, and (<b>d</b>) thermally treated mixtures of cathode and eggshell powders at different durations and temperatures. The leaching experiments were conducted at room temperature, with a solid/liquid ratio of 2% and a 1 h dissolution time.</p>
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<p>Results of reductive acid leaching for the recovery of desired elements under different conditions. The diagrams provide insights into (<b>a</b>) the effect of leaching time (with 3 M H<sub>2</sub>SO<sub>4</sub>, 3 vol.% H<sub>2</sub>O<sub>2</sub>, 10% solid/liquid ratio at room temperature), (<b>b</b>) the effect of sulfuric acid concentration (with 3 vol.% H<sub>2</sub>O<sub>2</sub>, 10% solid/liquid ratio at room temperature for 2 h), (<b>c</b>) the effect of hydrogen peroxide content (with 3 M H<sub>2</sub>SO<sub>4</sub>, 10% solid/liquid ratio at room temperature for 2 h), (<b>d</b>) the effect of solid/liquid ratio (with 3 M H<sub>2</sub>SO<sub>4</sub>, 3 vol.% H<sub>2</sub>O<sub>2</sub> at room temperature for 2 h), (<b>e</b>) the effect of leaching temperature (with 3 M H<sub>2</sub>SO<sub>4</sub>, 3 vol.% H<sub>2</sub>O<sub>2</sub>, 10% solid/liquid ratio for 2 h), and finally, (<b>f</b>) the effect of additional hydrogen peroxide content (with 2 M H<sub>2</sub>SO<sub>4</sub>, 10% solid/liquid at room temperature for 1 h).</p>
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<p>Mn precipitation across different pH values after a reaction time of 30 min at room temperature.</p>
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<p>Solvent extraction results with CYANEX 272 and n-heptane as a diluent: (<b>a</b>) extraction efficiency and (<b>b</b>) final-equilibrium pH after the extraction stage for different initial pH values (O/A = 1, n-heptane/CYANEX 272 = 3, room temperature, 10 min), (<b>c</b>) extraction efficiency and (<b>d</b>) final-equilibrium pH after the extraction stage versus degree of saponification (O/A = 1, n-heptane/CYANEX 272 = 4, room temperature, 10 min), (<b>e</b>) stripping results after the cobalt extraction stage for different H<sub>2</sub>SO<sub>4</sub> concentrations (O/A = 1, room temperature, 5 min), (<b>f</b>,<b>g</b>) phase separation after the extraction stage, and finally, (<b>h</b>) phase separation after the stripping stage.</p>
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<p>Results of Co stripping across different organic-/aqueous-phase ratios (0.5 M sulfuric acid solution, mixing time of 5 min at room temperature).</p>
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<p>Process flow diagram for hydrometallurgical recovery of the targeted elements from cathode active materials of a mixture of spent Li-ion batteries.</p>
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11 pages, 1460 KiB  
Article
Evaluation of the Effect of pH and Concentration of Calcium and Sulfate Ions on Coal Flotation
by Adrián A. González-Ibarra, Gloria I. Dávila-Pulido, Blanca R. González-Bonilla, Danay A. Charles, Jorge Carlos Ríos-Hurtado and Armando Salinas-Rodríguez
Minerals 2024, 14(11), 1118; https://doi.org/10.3390/min14111118 - 4 Nov 2024
Viewed by 472
Abstract
The presence of calcium sulfate in the process water during the coal flotation greatly influences the recovery and selectivity of the separation. The concentrations of calcium and sulfate ions modify mineral hydrophobicity by altering surface properties resulting in depression or activation of the [...] Read more.
The presence of calcium sulfate in the process water during the coal flotation greatly influences the recovery and selectivity of the separation. The concentrations of calcium and sulfate ions modify mineral hydrophobicity by altering surface properties resulting in depression or activation of the mineral species. An investigation to evaluate the statistical significance of the effect of the pH and concentration of calcium and sulfate ions on coal flotation was carried out; for this purpose, a 23 factorial design was implemented. A p-value < 0.05 was determined for the effect of calcium and sulfate ion concentrations, indicating that it is statistically significant. The interactions between factors (pH × calcium, pH × sulfate, calcium × sulfate and pH × calcium × sulfate) are also statistically significant, but the interaction between the concentration of calcium and sulfate ions has a notable influence according to the F statistic value. Employing 800 and 1920 mg/L of calcium and sulfate ions as experimental conditions yields a recovery of 90.4% with a concentrate containing 13% ash. Full article
(This article belongs to the Special Issue Interfacial Chemistry of Critical Mineral Flotation)
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<p>Preliminary test on coal flotation −150/+106 µm, 15% solids and pH 7. (<b>A</b>) Recovery as a function of time and (<b>B</b>) % ash as a function of time.</p>
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<p>Individual effects of pH, calcium and sulfate on the recovery (response variable) of coal flotation.</p>
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<p>Interaction matrix between: (<b>A</b>) calcium and sulfate, (<b>B</b>) calcium and pH, (<b>C</b>) sulfate and calcium, (<b>D</b>) sulfate and pH, (<b>E</b>) pH and calcium and (<b>F</b>) pH and sulfate on the recovery (response variable).</p>
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<p>Pareto chart of the standardized effects of the independent variables and their interactions on the response variable. (A) pH. (B) Calcium. (C) Sulfate.</p>
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<p>Recovery and ash content from coal flotation −150/+106 µm, 250 g/t collector and 100 g/t frother, 15% solids for 5 min: (<b>A</b>) pH 7 and (<b>B</b>) pH 9.</p>
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<p>X-ray diffraction pattern of the ash of a coal concentrate obtained at the experimental conditions of pH 9, 400 mg/L Ca<sup>2+</sup> and 1920 mg/L of SO<sub>4</sub><sup>2−</sup>.</p>
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12 pages, 2475 KiB  
Article
Calcium Phosphate Loaded with Curcumin Prodrug and Selenium Is Bifunctional in Osteosarcoma Treatments
by Mingjie Wang, Chunfeng Xu, Dong Xu, Chang Du and Yuelian Liu
J. Funct. Biomater. 2024, 15(11), 327; https://doi.org/10.3390/jfb15110327 - 3 Nov 2024
Viewed by 734
Abstract
Although SeO32− ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this [...] Read more.
Although SeO32− ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this study, SeO32− ions were co-precipitated in biomimetic calcium phosphate (Se@BioCaP), and modified curcumin prodrug (mcur) was adsorbed on diverse Se@BioCaP surfaces (mcur-Se@BioCaP-Ads). Co-precipitation yielded Se@BioCaP with a significantly higher Se content and exhibited a tailorable micro-/nanostructure. The favorable pH-responsive release of Se and mcur from mcur-Se@BioCaP-Ads showed a synergistic anticancer efficiency in OS cells, enhancing OS cell inhibition more than a single dose of them, which might be associated with ROS production in OS cells. In addition, increased alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 pre-osteoblasts were also verified. These results suggest this novel mcur-Se@BioCaP-Ads has promising and widespread potential in OS treatments. Full article
(This article belongs to the Special Issue Mesoporous Nanomaterials for Bone Tissue Engineering)
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Graphical abstract
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<p>Characterizations of BioCaP and Se@BioCaP. (<b>A</b>) BioCaP and Se@BioCaP crystals synthesized with different doses of Na<sub>2</sub>SeO<sub>3</sub> in mineralization solution; (<b>B</b>) BioCaP and Se@BioCaP crystal morphology of diverse Se@BioCaP crystals; (<b>C</b>) crystal atom percentage of Se in each Se@BioCaP sample; (<b>D</b>) crystal size of each Se@BioCaP sample. (<b>E</b>) TEM image and SAED pattern of BioCaP. (<b>F</b>) TEM image and SAED pattern of Se@BioCaP200 sample. Statistical difference: <span class="html-italic">* p</span> &lt; 0.05, <span class="html-italic">** p</span> &lt; 0.01, ns <span class="html-italic">p</span> &gt; 0.05.</p>
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<p>Drug loading and release rates of Se@BioCaP. (<b>A</b>) Na<sub>2</sub>SeO<sub>3</sub> content in diverse Se@BioCaP-Ads; (<b>B</b>) Na<sub>2</sub>SeO<sub>3</sub> release curves in acidic and neutral environments; (<b>C</b>,<b>D</b>) release curves of mcur absorbed on the surfaces of BioCaP or various Se@BioCaP carriers in pH 7.4 and pH 6.5.</p>
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<p>Viability of osteoblasts and OS cells after being treated by different materials. (<b>A</b>) Viability of pre-osteoblasts (MC3T3-E1) treated with BioCaP and diverse Se@BioCaPs; (<b>B</b>) viability of OS cells treated with BioCaP and diverse Se@BioCaPs; (<b>C</b>) viability of pre-osteoblasts (MC3T3-E1) treated with mcur-Se@BioCaP200-Ads at day 1, 2, and 4. (<b>D</b>) Viability of OS cells treated with mcur-SeBioCaP200-Ads at day 1, 2, and 4. Statistical difference: <span class="html-italic">* p</span> &lt; 0.05, <span class="html-italic">** p</span> &lt; 0.01, ns <span class="html-italic">p</span> &gt; 0.05.</p>
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<p>ROS staining of treated 143B cells in each group. Statistical difference: <span class="html-italic">** p</span> &lt; 0.01.</p>
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<p>Osteogenesis in each group. (<b>A</b>) ALP activity staining in each group on day 7, bar = 2 mm; (<b>B</b>) ALP activity of OB cells, <span class="html-italic">n</span> = 3; (<b>C</b>) ARS staining on day 14, bar = 2 mm. (<b>D</b>) Quantitative analysis of ARS staining on day 14, <span class="html-italic">n</span> = 3. Statistical difference: <span class="html-italic">* p</span> &lt; 0.05, <span class="html-italic">** p</span> &lt; 0.01.</p>
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16 pages, 7768 KiB  
Article
Genome-Wide Identification of the Cyclic Nucleotide-Gated Ion Channel Gene Family and Expression Profiles Under Low-Temperature Stress in Luffa cylindrica L.
by Jianting Liu, Yuqian Wang, Lijuan Peng, Mindong Chen, Xinru Ye, Yongping Li, Zuliang Li, Qingfang Wen and Haisheng Zhu
Int. J. Mol. Sci. 2024, 25(20), 11330; https://doi.org/10.3390/ijms252011330 - 21 Oct 2024
Viewed by 716
Abstract
Cyclic nucleotide-gated ion channels (CNGCs) are cell membrane channel proteins for calcium ions. They have been reported to play important roles in survival and in the responses to environmental factors in various plants. However, little is known about the CNGC family and its [...] Read more.
Cyclic nucleotide-gated ion channels (CNGCs) are cell membrane channel proteins for calcium ions. They have been reported to play important roles in survival and in the responses to environmental factors in various plants. However, little is known about the CNGC family and its functions in luffa (Luffa cylindrica L.). In this study, a bioinformatics-based method was used to identify members of the CNGC gene family in L. cylindrica. In total, 20 LcCNGCs were detected, and they were grouped into five subfamilies (I, II, Ⅲ, IV-a, and IV-b) in a phylogenetic analysis with CNGCs from Arabidopsis thaliana (20 AtCNGCs) and Momordica charantia (17 McCNGCs). The 20 LcCNGC genes were unevenly distributed on 11 of the 13 chromosomes in luffa, with none on Chromosomes 1 and 5. The members of each subfamily encoded proteins with highly conserved functional domains. An evolutionary analysis of CNGCs in luffa revealed three gene losses and a motif deletion. An examination of gene replication events during evolution indicated that two tandemly duplicated gene pairs were the primary driving force behind the evolution of the LcCNGC gene family. PlantCARE analyses of the LcCNGC promoter regions revealed various cis-regulatory elements, including those responsive to plant hormones (abscisic acid, methyl jasmonate, and salicylic acid) and abiotic stresses (light, drought, and low temperature). The presence of these cis-acting elements suggested that the encoded CNGC proteins may be involved in stress responses, as well as growth and development. Transcriptome sequencing (RNA-seq) analyses revealed tissue-specific expression patterns of LcCNGCs in various plant parts (roots, stems, leaves, flowers, and fruit) and the upregulation of some LcCNGCs under low-temperature stress. To confirm the accuracy of the RNA-seq data, 10 cold-responsive LcCNGC genes were selected for verification by quantitative real-time polymerase chain reaction (RT-qPCR) analysis. Under cold conditions, LcCNGC4 was highly upregulated (>50-fold increase in its transcript levels), and LcCNGC3, LcCNGC6, and LcCNGC13 were upregulated approximately 10-fold. Our findings provide new information about the evolution of the CNGC family in L. cylindrica and provide insights into the functions of the encoded CNGC proteins. Full article
(This article belongs to the Special Issue Transcription Factors in Plant Gene Expression Regulation)
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Figure 1
<p>Chromosomal location of <span class="html-italic">L. cylindrica CNGC</span> genes. The scale is shown on the left. Tandemly repeated genes are marked in red.</p>
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<p>Analysis of <span class="html-italic">L. cylindrica CNGC</span> gene promoter regions and gene structures. (<b>a</b>) <span class="html-italic">CNGC</span> gene promoters in <span class="html-italic">L. cylindrica</span>. (<b>b</b>) <span class="html-italic">CNGC</span> gene structures in <span class="html-italic">L. cylindrica</span>.</p>
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<p>Phylogenetic tree and motif analysis of <span class="html-italic">CNGC</span> genes in <span class="html-italic">L. cylindrica</span>. (<b>a</b>) Phylogenetic tree constructed using the maximum-likelihood method using MEGA 7.0. (<b>b</b>) Motifs in luffa <span class="html-italic">CNGC</span> genes predicted using MEME; the sequence and length of each motif are shown.</p>
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<p><span class="html-italic">CNGC</span> gene transcript profiles in <span class="html-italic">L. cylindrica</span>. (<b>a</b>) Tissue-specific transcript profiles of <span class="html-italic">L. cylindrica CNGC</span> genes. (<b>b</b>) <span class="html-italic">CNGC</span> transcript profiles in <span class="html-italic">L. cylindrica</span> in response to cold stress.</p>
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<p>Quantitative real-time polymerase chain reaction (RT-qPCR) analysis of transcript levels (RNA-seq) of selected <span class="html-italic">LcCNGC</span> genes in luffa leaf under low-temperature stress. The <span class="html-italic">18s rRNA</span> gene was used as an internal control. Error bars represent the standard error of three biological replicates. Lowercase letters indicate RT-qPCR analyses’ significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Regression analysis of fold-change values determined using RNA sequencing and RT-qPCR analyses. Regression analyses of transcript levels of <span class="html-italic">CNGC</span> genes after low-temperature stress as determined from RNA sequencing data and RT-qPCR analyses. For RNA sequencing data, the fold-change value was calculated as the ratio of the FPKM value for the stress-treated sample. For RT-qPCR data, the fold-change value was calculated by normalizing the transcript level in the stress-treated sample against that in the control.</p>
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<p>Subcellular localization of the LcCNGC protein. (<b>a</b>) Vector construction of pCAMBIA1300-<span class="html-italic">LcCNGC13-GFP</span>. (<b>b</b>) Green fluorescence, visible light, and merged green fluorescence and visible light images are shown. <span class="html-italic">35S</span>::<span class="html-italic">GFP</span>: <span class="html-italic">Agrobacterium tumefaciens</span> strain carrying the empty vector (pCAMBIA1300-<span class="html-italic">GFP</span>); <span class="html-italic">35S</span>::<span class="html-italic">LcCNGC</span>::<span class="html-italic">GFP</span>: <span class="html-italic">A. tumefaciens</span> strain carrying a recombinant vector (pCAMBIA1300-<span class="html-italic">LcCNGC13-GFP</span>). Scale bars = 50 µM.</p>
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16 pages, 2049 KiB  
Article
Potentiometric Electronic Tongue for the Evaluation of Multiple-Unit Pellet Sprinkle Formulations of Rosuvastatin Calcium
by Patrycja Ciosek-Skibińska, Krzysztof Cal, Daniel Zakowiecki and Joanna Lenik
Materials 2024, 17(20), 5016; https://doi.org/10.3390/ma17205016 - 14 Oct 2024
Viewed by 660
Abstract
Sprinkle formulations represent an interesting genre of medicinal products. A frequent problem, however, is the need to mask the unpleasant taste of these drug substances. In the present work, we propose the use of a novel sensor array based on solid-state ion-selective electrodes [...] Read more.
Sprinkle formulations represent an interesting genre of medicinal products. A frequent problem, however, is the need to mask the unpleasant taste of these drug substances. In the present work, we propose the use of a novel sensor array based on solid-state ion-selective electrodes to evaluate the taste-masking efficiency of rosuvastatin (ROS) sprinkle formulations. Eight Multiple Unit Pellet Systems (MUPSs) were analyzed at two different doses (API_50) and (API_10), as well as pure Active Pharmaceutical Ingredient (API) as a bitter standard. Calcium phosphate-based starter pellets were coated with the mixture containing rosuvastatin. Some of them were additionally coated with hydroxypropyl methylcellulose, which was intended to separate the bitter substance and prevent it from coming into contact with the taste buds. The sensor array consisted of 16 prepared sensors with a polymer membrane that had a different selectivity towards rosuvastatin calcium. The main analytical parameters (sensitivity, selectivity, response time, pH dependence of potential, drift of potential, lifetime) of the constructed ion-selective electrodes sensitive for rosuvastatin were determined. The signals from the sensors array recorded during the experiments were processed using Principal Component Analysis (PCA). The results obtained, i.e., the chemical images of the pharmaceutical samples, indicated that the electronic tongue composed of the developed solid-state electrodes provided respective attributes as sensor signals, enabling both of various kinds of ROS pellets to be distinguished and their similarity to ROS bitterness standards to be tested. Full article
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Figure 1
<p>Rosuvastatin((3R,5S,6E)-7-[4-(4-fluorophenyl)-2-(N-ethylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-ene acid).</p>
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<p>Schematic presentation of ISE and potentiometric sensor array.</p>
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<p>Dynamic response for electrodes no. 5, 6, 10 (<b>a</b>) and for electrodes no. 11 and 12 (<b>b</b>).</p>
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<p>Potential drift of the selected electrodes in 2 × 10<sup>−4</sup> mol L<sup>−1</sup> rosuvastatin solution during one hour.</p>
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<p>Effect of the pH on the potential response of the selected electrodes in 2 × 10<sup>−4</sup> mol L<sup>−1</sup> of rosuvastatin solution.</p>
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<p>Stability of sensitivity of the electrode no. 11 in time.</p>
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<p>PCA score plot of electronic tongue results for the studied formulations (A–H). and pure API (API_10 and API_50).</p>
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<p>PC1 values of the electronic tongue results showing gradually changing characteristics of the studied formulations (A–H), compared to pure API standards (API_10 and API_50).</p>
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<p>HCA showing the discrimination of ROS samples. Dashed lines represent a division into 2 groups at variance weighted distance &gt; 30, and 3 groups at variance weighted distance ~20.</p>
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16 pages, 4912 KiB  
Article
The Endocannabinoid Peptide RVD-Hemopressin Is a TRPV1 Channel Blocker
by Constanza Suárez-Suárez, Sebastián González-Pérez, Valeria Márquez-Miranda, Ingrid Araya-Duran, Isabel Vidal-Beltrán, Sebastián Vergara, Ingrid Carvacho and Fernando Hinostroza
Biomolecules 2024, 14(9), 1134; https://doi.org/10.3390/biom14091134 - 8 Sep 2024
Viewed by 930
Abstract
Neurotransmission is critical for brain function, allowing neurons to communicate through neurotransmitters and neuropeptides. RVD-hemopressin (RVD-Hp), a novel peptide identified in noradrenergic neurons, modulates cannabinoid receptors CB1 and CB2. Unlike hemopressin (Hp), which induces anxiogenic behaviors via transient receptor potential vanilloid 1 (TRPV1) [...] Read more.
Neurotransmission is critical for brain function, allowing neurons to communicate through neurotransmitters and neuropeptides. RVD-hemopressin (RVD-Hp), a novel peptide identified in noradrenergic neurons, modulates cannabinoid receptors CB1 and CB2. Unlike hemopressin (Hp), which induces anxiogenic behaviors via transient receptor potential vanilloid 1 (TRPV1) activation, RVD-Hp counteracts these effects, suggesting that it may block TRPV1. This study investigates RVD-Hp’s role as a TRPV1 channel blocker using HEK293 cells expressing TRPV1-GFP. Calcium imaging and patch-clamp recordings demonstrated that RVD-Hp reduces TRPV1-mediated calcium influx and TRPV1 ion currents. Molecular docking and dynamics simulations indicated that RVD-Hp interacts with TRPV1’s selectivity filter, forming stable hydrogen bonds and van der Waals contacts, thus preventing ion permeation. These findings highlight RVD-Hp’s potential as a therapeutic agent for conditions involving TRPV1 activation, such as pain and anxiety. Full article
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<p>RVD-Hp reduces the calcium influx in HEK293-transfected cells. Representative traces of the Fura red ratio (405 nm/488 nm) in (<b>A</b>) HEK293-untransfected cells (n: 26) and -transfected cells after (<b>B</b>) DMSO (n: 20), (<b>C</b>) 1 µM cap (n: 58), (<b>D</b>), 1 µM cap + 10 µM RVD-Hp (n: 60), (<b>E</b>) 1µM cap + 10 µM SB366791 (n: 20), (<b>F</b>) 10 µM RVD-Hp (n: 59), and (<b>G</b>) 10 µM SB366791 (n: 51) administration. (<b>H</b>) Mean amplitude of Fura Red ratio (405 nm/488 nm) calculated in the last minute of the experiment (mean ± SEM). *: Comparison to DMSO, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001. &amp;: Comparison to Cap, &amp; <span class="html-italic">p</span> &lt; 0.05, &amp;&amp;&amp;&amp; <span class="html-italic">p</span> &lt; 0.0001. <span>$</span>: Comparison to Cap + RVD-Hp, <span>$</span><span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.0001. #: Comparison to Cap + SB366791, ## <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>RVD-Hp is a TRPV1 channel blocker. (<b>A</b>) Comparison of current fold change measured at +80 mV in response to Cap (1 µM). (<b>B</b>) Representative traces of TRPV1 channel currents in response to a voltage ramp in the presence of 1 µM Cap (blue line), 1 µM Cap + 10 µM RVD-Hp (purple line), 1 µM Cap + 10 µM SB366791 (dark pink line), 10 µM RVD-Hp (pink line), and 10 µM SB36671 (yellow line). (<b>C</b>) Representative current (nA) versus voltage (mV) plot for all tested conditions. (<b>D</b>) Average outward current fold change amplitude at +80 mV (Control n: 7; Cap n: 7; Cap + RVD-Hp n: 4; Cap + SB366791 n: 4; RVD-Hp n: 4; SB366791 n: 3). *: Comparison to control, * <span class="html-italic">p</span> &lt; 0.0186. ** <span class="html-italic">p</span> &lt; 0.01. **** <span class="html-italic">p</span> &lt; 0.0001. &amp;: Comparison to capsaicin. &amp; <span class="html-italic">p</span> &lt; 0.0214, &amp;&amp;&amp;&amp; <span class="html-italic">p</span> &lt; 0.0001. <span>$</span>: Comparison to capsaicin + RVD-Hp. <span>$</span> <span class="html-italic">p</span> &lt; 0.0323. (<b>E</b>) Average concentration–response curve for RVD-Hp (1, 10, 20, and 50 µM, mean ± SEM).</p>
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<p>RVD-Hp interacts with the selectivity filter of the TRPV1 channel. (<b>A</b>) TRPV1-RVD-Hp docking results using HADDOCK2.4. (<b>B</b>) RVD-Hp (red)–TRPV1 channel (gray)–capsaicin (yellow) interaction at 1 µs of simulation. (<b>B’</b>) RVD-Hp (pink) contacts amino acids forming the TRPV1 channel selectivity filter.</p>
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<p>TRPV1 channel–RVD-Hp molecular interaction. (<b>A</b>) Flare plot showing all the amino acids involved in the RVD-Hp binding. Thicker lines represent contacts present for a longer period of time in the simulation. Peptide amino acids are colored in red. The number of (<b>B</b>) hydrogen bonds and (<b>C</b>) Van der Waals contacts throughout the simulation. (<b>D</b>) Contact area of interaction. (<b>E</b>) Binding free energy of the TRPV1 channel–RVD-Hp interaction.</p>
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<p>RVD-Hp prevents ion permeation. (<b>A</b>) Pore radius at 1 µs of simulation. (<b>B</b>) Potential through the pore. (<b>C</b>) Ion total density and (<b>D</b>) local density/total density in the pore. Ions present close to the pore in the TRPV1 channel (<b>E</b>) without and (<b>F</b>) with RVD-Hp. (<b>E</b>,<b>F</b>) Each line represents a different K<sup>+</sup> ion. Black line: TRPV1 without RVD-Hp. Red line: TRPV1 with RVD-Hp.</p>
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19 pages, 4650 KiB  
Review
TRPA1-Related Diseases and Applications of Nanotherapy
by Dongki Yang
Int. J. Mol. Sci. 2024, 25(17), 9234; https://doi.org/10.3390/ijms25179234 - 26 Aug 2024
Viewed by 774
Abstract
Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member [...] Read more.
Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member of the TRPA family, is a calcium ion affinity non-selective cation channel involved in sensory transduction and responds to odors, tastes, and chemicals. It also regulates temperature and responses to stimuli. Recent studies have linked TRPA1 to several disorders, including chronic pain, inflammatory diseases, allergies, and respiratory problems, owing to its activation by environmental toxins. Mutations in TRPA1 can affect the sensory nerves and microvasculature, potentially causing nerve pain and vascular problems. Understanding the function of TRPA1 is important for the development of treatments for these diseases. Recent developments in nanomedicines that target various ion channels, including TRPA1, have had a significant impact on disease treatment, providing innovative alternatives to traditional disease treatments by overcoming various adverse effects. Full article
(This article belongs to the Special Issue TRP Channels in Physiology and Pathophysiology 2.0)
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<p>TRPA1 has four subunits and six transmembrane helices. It has 16 ankyrin repeats at the N-terminus important for sensitivity to chemicals and temperature. Three cysteines (C621, C641, and C665) and one lysine (K710) are modified by electrophiles (e.g., AITC, cinnamaldehyde, cuminaldehyde, anisaldehyde, and tiglic aldehyde) to activate TRPA1. Non-electrophiles (e.g., menthol, carvacrol, clotrimazole, thymol, decanol, 2-ethyl-1-hexanol, toluene, and α-terpineol) activate it by binding to the S5/S6 domains. This activation mode is crucial for sensing temperature, texture, and pungency. Green arrow: TRPA1 activation, orange arrow: external calcium ion influx due to TRPA1 activation.</p>
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<p>Application of nanotechnology in breast cancer and PMA treatment targeting TRPA1 inhibition. (<b>a</b>) Nanoparticle-encapsulated antagonist DIPMA-MK-3207, a pH-responsive nanoparticle targeting endosomal CLR/RAMP1, enhances CGRP-induced pain relief efficacy by blocking TRPA1-related signaling.; (<b>b</b>) photothermal conjugated polymer nanoparticles (NPs-H) encapsulating HC-030031 (HC), a specific inhibitor of the near-infrared (NIR)-responsive TRPA1 ion channel, block the formation of Ca<sup>2+</sup>/CaM complexes when exposed to an 808 nm laser. As a result, chemotherapy resistance is reduced and tumor cell death is promoted. Red arrows: Pathway of disease suppression by nanoparticles, blue arrows: Pathway of disease development by TRPA1 activation.</p>
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<p>Application of nanotechnology in MS and KOA treatment targeting TRPA1 inhibition. (<b>a</b>) The use of solid lipid nanoparticles (SLNs) to deliver anti-inflammatory drugs with poor bioavailability could improve drug stability and delivery, potentially enabling effective MS treatment to prevent demyelination by inhibiting the TRPA1/NF-kB/GFAP signaling pathway.; (<b>b</b>) Nanoemulsion (SP-NE) with excellent stability, manufactured by extracting essential oil from pickling powder, a herbal medicine for KOA, through a high-pressure homogenization process, alleviates KOA synovitis by negatively regulating TRPA1 through AMPK-mTOR signaling. Red arrows: Pathway of disease suppression by nanoparticles, blue arrows: Pathway of disease development by TRPA1 activation.</p>
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<p>Application of nanotechnology on tumor and diabetes treatment targeting TRPA1 activation. Tumor: NIR light-irradiated silica nanoparticles (MSNs) with tumor cell targeting properties, I/B@MSN-T@HA (light-controlled Ca<sup>2+</sup> na-modulator), trigger ROS generation and Ca<sup>2+</sup> influx through TRPA1 channels. This approach maximizes intracellular Ca<sup>2+</sup> concentration, resulting in mitochondrial dysfunction, ATP reduction, and tumor cell death (red arrows); ROS generation, and photothermal effects are exposed to an 808 nm laser, they generate ROS and local heat to activate the TRPA1 ion channel. Ca<sup>2+</sup> introduced into cells by activation increases GLP-1 secretion and lowers blood sugar levels (blue arrows).</p>
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16 pages, 1090 KiB  
Review
Quantification of Ions in Human Urine—A Review for Clinical Laboratories
by Ana Rita Ferrão, Paula Pestana, Lígia Borges, Rita Palmeira-de-Oliveira, Ana Palmeira-de-Oliveira and José Martinez-de-Oliveira
Biomedicines 2024, 12(8), 1848; https://doi.org/10.3390/biomedicines12081848 - 14 Aug 2024
Viewed by 1047
Abstract
Urine is an organic fluid produced by the kidney, and its analysis is one of the most requested laboratory tests by clinicians. The ionic composition of urine has been shown to be a good health indicator: it is useful for the diagnosis of [...] Read more.
Urine is an organic fluid produced by the kidney, and its analysis is one of the most requested laboratory tests by clinicians. The ionic composition of urine has been shown to be a good health indicator: it is useful for the diagnosis of several diseases, as well as monitoring therapeutics. This review considers laboratorial techniques that have been used throughout time for the quantification of ions in urine, and also considers some methodologies that can potentially be used in clinical laboratories for this kind of analysis. Those methods include gravimetry, titration, flame emission spectrophotometry (flame photometry), fluorimetry, potentiometry (ion selective electrodes), ion chromatography, electrophoresis, kinetic colorimetric tests, enzymatic colorimetric tests, flow cytometry, atomic absorption, plasma atomic emission spectrometry, and paper-based devices. Sodium, potassium, chloride, calcium, and magnesium are among the most important physiological ions, and their determination is frequently requested in hospitals. There have been many advances regarding the analysis of these ions in 24 h urine. However, there is still some way to go concerning the importance of intracellular ions in this type of sample as well as the use of occasional urine for monitoring these parameters. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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<p>Diagram explanation for the methodology of flame emission spectrophotometry.</p>
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<p>Diagram representation of the various types of the most used materials for potentiometric analysis.</p>
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<p>Chronological scheme that reflects the appearance of the different quantitative methodologies addressed over time.</p>
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15 pages, 4520 KiB  
Article
A Feature Selection-Incorporated Simulation Study to Reveal the Effect of Calcium Ions on Cardiac Repolarization Alternans during Myocardial Ischemia
by Kaihao Gu, Zihui Geng, Yuwei Yang, Shengjie Yan, Bo Hu and Xiaomei Wu
Appl. Sci. 2024, 14(15), 6789; https://doi.org/10.3390/app14156789 - 3 Aug 2024
Viewed by 795
Abstract
(1) Background: The main factors and their interrelationships contributing to cardiac repolarization alternans (CRA) remain unclear. This study aimed to elucidate the calcium (Ca2+)-related mechanisms underlying myocardial ischemia (MI)-induced CRA. (2) Materials and Methods: CRA was induced using S1 stimuli for [...] Read more.
(1) Background: The main factors and their interrelationships contributing to cardiac repolarization alternans (CRA) remain unclear. This study aimed to elucidate the calcium (Ca2+)-related mechanisms underlying myocardial ischemia (MI)-induced CRA. (2) Materials and Methods: CRA was induced using S1 stimuli for pacing in an in silico ventricular model with MI. The standard deviations of nine Ca2+-related subcellular parameters among heartbeats from 100 respective nodes with and without alternans were chosen as features, including the maximum systole and end-diastole and corresponding differences in the Ca2+ concentration in the intracellular region([Ca2+]i) and junctional sarcoplasmic reticulum ([Ca2+]jsr), as well as the maximum opening of the L-type Ca2+ current (ICaL) voltage-dependent activation gate (d-gate), maximum closing of the inactivation gate (ff-gate), and the gated channel opening time (GCOT). Feature selection was applied to determine the importance of these features. (3) Results: The major parameters affecting CRA were the differences in [Ca2+]i at end-diastole, followed by the extent of d-gate activation and GCOT among beats. (4) Conclusions: MI-induced CRA is primarily characterized by functional changes in Ca2+ re-uptake, leading to alternans of [Ca2+]i and subsequent alternans of ICaL-dependent properties. The combination of computational simulation and machine learning shows promise in researching the underlying mechanisms of cardiac electrophysiology. Full article
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<p>Flow diagram of the overall research methodology. The blue area in the myocardial ischemia model denotes the ischemic region.</p>
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<p>The rabbit ventricular model featuring (<b>a</b>) the His–Purkinje system and (<b>b</b>) myocardial ischemia. The red dot in (<b>a</b>) represents the starting point of His bundle. The red and blue regions in (<b>b</b>) represent the ICZ and the BZ, respectively.</p>
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<p>The virtual lead II ECG of the ventricular model under cycle lengths of (<b>a</b>) 600 ms and (<b>b</b>) 330 ms.</p>
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<p>Examples of (<b>a</b>) alternans and (<b>b</b>) non-alternans in cardiomyocyte action potential (teal trace) and [Ca<sup>2+</sup>]<sub>i</sub> (brown trace). The wave crest (red circle) and trough (blue asterisk) of [Ca<sup>2+</sup>]<sub>i</sub> among beats are marked under (<b>c</b>) alternans and (<b>d</b>) non-alternans.</p>
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<p>Examples of (<b>a</b>) alternans and (<b>b</b>) non-alternans in cardiomyocytes action potential (teal trace) and [Ca<sup>2+</sup>]<sub>jsr</sub> (brown trace). The wave crest (red circle) and trough (blue asterisk) of [Ca<sup>2+</sup>]<sub>jsr</sub> among beats are marked under (<b>c</b>) alternans and (<b>d</b>) non-alternans.</p>
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<p>Examples of (<b>a</b>) alternans and (<b>b</b>) non-alternans in cardiomyocyte action potential (teal trace) and states of the d-gate (brown trace), along with the same traces of cardiomyocyte action potential (teal trace) and states of ff-gate (brown trace) under (<b>c</b>) alternans and (<b>d</b>) non-alternans.</p>
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<p>Examples of the states of the d-gate under (<b>a</b>) alternans and (<b>b</b>) non-alternans, along with the states of the ff-gate under (<b>c</b>) alternans and (<b>d</b>) non-alternans. The blue circles in the d-gate represent wave crests. The green asterisks in the ff-gate represent wave troughs.</p>
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<p>States of the ff-gate, d-gate, and gated channel.</p>
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<p>Ranking of the importance of features affecting CRA.</p>
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<p>Mechanistic flowchart of the major Ca<sup>2+</sup>-related subcellular parameters leading to CRA. The arrows inside the flowchart elements indicate an increase or decrease in the associated parameter; while those outside the elements indicate the direction of effect between different parameters.In the context of a fixed activation cycle, shortened APD corresponds to a longer DI (currently even beats), which provides relatively sufficient time to largely compensate for the elevated [Ca<sup>2+</sup>]<sub>i</sub> caused by decreased cardiomyocyte calcium re-uptake. This results in lower [Ca<sup>2+</sup>]<sub>i</sub>, improved I<sub>CaL</sub> channel restoration, larger calcium inward flow, which increases AP amplitude and APD, and GCOT in the following beat (currently odd beats). In addition to the inherent decline in SERCA pump function, the reduced DI combined with lengthened APD further suppresses Ca<sup>2+</sup> re-uptake in the next beat, forming alternans of [Ca<sup>2+</sup>]<sub>i</sub>, voltage gates, and GCOT among adjacent beats. Among these parameters, alternans of [Ca<sup>2+</sup>]<sub>i</sub> at end-diastole always occurs first as it directly reflects the situation of Ca<sup>2+</sup> re-uptake, making it the most important factor contributing to CRA. The activation and opening time of the I<sub>CaL</sub> channel significantly determine the amount of current flow responsible for the subsequent generation of AP. From <a href="#applsci-14-06789-f008" class="html-fig">Figure 8</a>, it is evident that state switching is more intensive for the d-gate. Therefore, a shorter total opening time, along with the impacts from AP, I<sub>CaL</sub>, and GCOT involved in the positive feedback loop, makes the importance of the d-gate higher than the ff-gate.</p>
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17 pages, 778 KiB  
Review
An Update on Polyphosphate In Vivo Activities
by Robert Schoeppe, Moritz Waldmann, Henning J. Jessen and Thomas Renné
Biomolecules 2024, 14(8), 937; https://doi.org/10.3390/biom14080937 - 2 Aug 2024
Viewed by 1225
Abstract
Polyphosphate (polyP) is an evolutionary ancient inorganic molecule widespread in biology, exerting a broad range of biological activities. The intracellular polymer serves as an energy storage pool and phosphate/calcium ion reservoir with implications for basal cellular functions. Metabolisms of the polymer are well [...] Read more.
Polyphosphate (polyP) is an evolutionary ancient inorganic molecule widespread in biology, exerting a broad range of biological activities. The intracellular polymer serves as an energy storage pool and phosphate/calcium ion reservoir with implications for basal cellular functions. Metabolisms of the polymer are well understood in procaryotes and unicellular eukaryotic cells. However, functions, regulation, and association with disease states of the polymer in higher eukaryotic species such as mammalians are just beginning to emerge. The review summarises our current understanding of polyP metabolism, the polymer’s functions, and methods for polyP analysis. In-depth knowledge of the pathways that control polyP turnover will open future perspectives for selective targeting of the polymer. Full article
(This article belongs to the Special Issue Inorganic Polyphosphate: A Multifaceted Biomolecule)
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<p>Gross structures of natural polyP. (<b>A</b>): PolyP is a polymer consisting of 3–1000 tetrahedral phosphate subunits linked to each other via a shared oxygen atom. Most polyP is linear; however, branched forms exist. (<b>B</b>): PolyP binds Ca<sup>2+</sup>, which binds further polyP and lines up, presumably in a helical secondary structure [<a href="#B27-biomolecules-14-00937" class="html-bibr">27</a>]. (<b>C</b>): Aggregated Ca<sup>2+</sup> polyP forms nanoparticles that, in turn, form microsomes within cells.</p>
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34 pages, 8232 KiB  
Review
Voltage-Gated K+ Channel Modulation by Marine Toxins: Pharmacological Innovations and Therapeutic Opportunities
by Rita Turcio, Francesca Di Matteo, Ilaria Capolupo, Tania Ciaglia, Simona Musella, Carla Di Chio, Claudio Stagno, Pietro Campiglia, Alessia Bertamino and Carmine Ostacolo
Mar. Drugs 2024, 22(8), 350; https://doi.org/10.3390/md22080350 - 29 Jul 2024
Cited by 1 | Viewed by 1172
Abstract
Bioactive compounds are abundant in animals originating from marine ecosystems. Ion channels, which include sodium, potassium, calcium, and chloride, together with their numerous variants and subtypes, are the primary molecular targets of the latter. Based on their cellular targets, these venom compounds show [...] Read more.
Bioactive compounds are abundant in animals originating from marine ecosystems. Ion channels, which include sodium, potassium, calcium, and chloride, together with their numerous variants and subtypes, are the primary molecular targets of the latter. Based on their cellular targets, these venom compounds show a range of potencies and selectivity and may have some therapeutic properties. Due to their potential as medications to treat a range of (human) diseases, including pain, autoimmune disorders, and neurological diseases, marine molecules have been the focus of several studies over the last ten years. The aim of this review is on the various facets of marine (or marine-derived) molecules, ranging from structural characterization and discovery to pharmacology, culminating in the development of some “novel” candidate chemotherapeutic drugs that target potassium channels. Full article
(This article belongs to the Special Issue Marine Drug Research in Italy)
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<p>Schematic representation of the proposed transmembrane topology of voltage-gated ion channels. (<b>A</b>) The α-subunit of K<sup>+</sup> channels showing the transmembrane segments (1–6) spanning the cell membrane. Segment 4 (red color) represents the voltage sensor. In the extracellular region, the S5-S6 P-loop is directly involved in the ion conduction pathway. In the intracellular region, the N and C termini ends of the polypeptide appear. The right panel shows the top and side views of homo- or heterotetramers of encircled four-fold α-subunits forming the central ion conduction pathway of a K<sup>+</sup> channel. (<b>B</b>) A single subunit polypeptide of four homologous domains (I–IV) forming a functional pore of Ca<sup>2+</sup> and Na<sup>+</sup> channels. (<b>C</b>) K<sub>v</sub>1.2 channel structural models in activated and resting states X-ray crystallography were used to identify the structure of the K<sub>v</sub>1.2 channel in an activated state, and the ROSETTA membrane technique was used to predict the channel’s structure in a closed state. The voltage-sensing and pore-forming modules consist of two subunits. Take note of the labels that show how the voltage-sensing module of subunit 4 connects with the subunit 1 pore-forming module (left) and how the subunit 2 voltage-sensing module interacts with the subunit 3 pore-forming module (right). S1, dark blue; S2, light blue-green; S3, light green; S4, dark green; S5, yellow-green; and S6, orange, are the colored transmembrane segments. The S4–S5 linkers covalently connecting pore-forming and voltage-sensing modules are highlighted in magenta [<a href="#B7-marinedrugs-22-00350" class="html-bibr">7</a>].</p>
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<p>According to the “ball and chain” model of inactivation, the ion channels contain a domain (“ball”) tethered to the cytoplasmatic side of the protein. Following a conformational change, the inactivation ball is free to bind to its receptor, occluding the ion-conducting pore. This fast inactivation process (N-type inactivation) can be distinguished for K<sup>+</sup> channels from a second inactivation process (C-type inactivation), which involves a conformational change in the extracellular part of the protein. The K<sup>+</sup> is depicted as a green circle [<a href="#B12-marinedrugs-22-00350" class="html-bibr">12</a>].</p>
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<p>Twenty of the most abundant <span class="html-italic">Conus</span> species in the South China Sea [<a href="#B34-marinedrugs-22-00350" class="html-bibr">34</a>].</p>
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<p>A structural schematic illustration to show the classification of conotoxins into superfamilies and their ion channel targets.</p>
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<p>Primary structure of conotoxins binding to voltage-gated ion channels. (<b>A</b>) µ- and δ-conotoxins (2EFZ, 1FUE) interact with Na<sup>+</sup> channels, ω- with Ca<sup>2+</sup> channels, and κ- with K<sup>+</sup> channels (1TTL, 1KCP). K<sup>+</sup> channel peptide blockers seem to possess a common functionally important dyad consisting of a hydrophobic residue and key lysine protruding from a relatively flat surface [<a href="#B45-marinedrugs-22-00350" class="html-bibr">45</a>]. (<b>B</b>) These residues are highlighted in bold in the κ-PVIIA primary sequence [<a href="#B41-marinedrugs-22-00350" class="html-bibr">41</a>,<a href="#B46-marinedrugs-22-00350" class="html-bibr">46</a>].</p>
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<p>A comparison of O-superfamily precursor sequences. The conserved cysteine pattern is illustrated in bold. The inferred sequence of the μO-conotoxin MrVIB precursor sequence is aligned with the prepropeptide sequences of Δ-conotoxin TxVIA (formerly called the King-Kong peptide), ω-conotoxin GVIA, and к-PVIIA. The conserved amino acids are illustrated with a grey background.</p>
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<p>Sequence alignment of κM-conotoxins RIIIK and RIIIJ with other M-superfamily peptides and κ-conotoxin PVIIA. O represents 4-hydroxyproline and * an amidated C-terminal amino acid.</p>
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<p>(<b>A</b>) Sequence alignment of chosen Kunitz-fold peptides (Conk-S1 and Conk-S2). Grey shading indicates conserved cysteine residues. Two preserved disulfide bridges are shown in solid lines. A dotted line indicates a third, non-conserved bridge. The secondary structure elements are illustrated at the bottom. A non-conserved arginine identified as a critical residue for channel block is denoted by an asterisk. The bioactive residues of both Conk-S1 and Conk-S2 from <span class="html-italic">Conus Striatus,</span> are highlighted in red. (<b>B</b>) Ribbon representations of Conk-S1 (PDB: 2CA7) and Conk-S2 (PDB: 2J6D). The yellow line represents disulfide bridges. The bioactive residues of Conk-S1 are highlighted in (<b>A</b>).</p>
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<p>Molecular structures of CPY conopeptides. Tyrosine residues are evidenced in bold.</p>
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<p>(<b>A</b>) Peptide sequence of pl14a showing the disulfide connectivity. (<b>B</b>) Disulfide motifs found in conotoxin superfamilies with four cysteines.</p>
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<p>Comparison of peptide sr11a with other I-conotoxins from vermivorous species. γ, gamma-carboxy-glutamate; O, hydroxyPro; S, glycosylated Ser; *, amidated C-terminus [<a href="#B75-marinedrugs-22-00350" class="html-bibr">75</a>].</p>
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<p>The sea anemone mature peptide sequences resemble β-defensin. The conserved cysteine residues are marked with red writing on a grey background. Tentacles, column, mesenterial filaments, and combinations are represented by letters T, C, F, and M, which are emphasized in blue, orange, green, and yellow, respectively. Homology modeling predicts various mature peptides from sea anemones using CgNa (PDB 2H9X), BDS-I (PDB 1BDS), and APETx2 (PDB 2MUB).</p>
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<p>Amino acid sequences of a new family of sea anemone peptide toxins. Charged residues are bolded in red. The sequence identities are highlighted in yellow.</p>
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<p>(<b>A</b>) Alignment of sea anemone toxins, which most likely have an ICK fold. Predicted disulfide connectivities are illustrated with dotted lines. Amino acid identities are highlighted in yellow and similarities in bold. The toxin sequences given are BcsTx3 (κ-actitoxin-Bcs4a; UniProt C0HJC4), NvePTx1 (U-EWTX-NvePTx1; UniProt A7RMN1), MsePTx1 (U-metritoxin-Msn2a; UniProt P0DMD7), and PhcrTx1 (π-phymatoxin-Pcf1a; UniProt C0HJB1) [<a href="#B78-marinedrugs-22-00350" class="html-bibr">78</a>]. (<b>B</b>) Structures of BscTx1 and BscTx2 type-1 toxins. Disulfide bridges are illustrated by dotted lines.</p>
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<p>Alignment of the amino acid sequence of AETXk with those of the known type 1 potassium channel toxins from sea anemones: HmK, ShK, AeK, AsKS, and BgK. The residues identical with AETXk are highlighted. Disulfide bridges are depicted by dotted lines. Asterisks represent the amino acid dyad that is crucial for the binding to potassium channels.</p>
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<p>Amino acid sequences of Kuntitz-type peptides APEKTx1, SHTX-III, and AsKC1–3. Shaded areas indicate spots that are highly conserved. α-dendrotoxin (a K<sup>+</sup> channel-blocking toxin from the green mamba <span class="html-italic">Dendroaspis angusticeps</span>) and BPTI (bovine pancreatic trypsin inhibitor, the first-described Kunitz protein) are depicted as reference compounds. The three disulfide bridges are represented by a dotted line, and the cysteine residues involved are highlighted in red [<a href="#B119-marinedrugs-22-00350" class="html-bibr">119</a>].</p>
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<p>Disulfide bonds in Ate1a (PDB 6AZA) are depicted as orange tubes, with N- and C-termini labeled [<a href="#B55-marinedrugs-22-00350" class="html-bibr">55</a>].</p>
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<p>Domain structure of Ate1a and Ate1a-like contigs. Prepropeptides consist of a signal peptide (SignalP), one or two cysteine-containing propeptide domains (CysProP), and three cysteine-free propeptide domains (LinearProP), each preceding an Ate1a-like PHAB domain [<a href="#B95-marinedrugs-22-00350" class="html-bibr">95</a>].</p>
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<p>Primary sequence of the kP-crassipeptides. Cysteine residues are highlighted and aligned.</p>
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<p>Structure of 4,5-dibromopyrrole-2-carboxylic acid.</p>
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<p>The chemical structures of pyrrole alkaloids <b>1</b>–<b>11</b> from Agelas sponges.</p>
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<p>Structure of Acredinones A and B.</p>
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<p>Structure of gambierol toxin, showing the eight polyether rings.</p>
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<p>Aplysiatoxins’ molecular structures.</p>
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18 pages, 2482 KiB  
Article
Thermodynamic and Kinetic Studies of the Precipitation of Double-Doped Amorphous Calcium Phosphate and Its Behaviour in Artificial Saliva
by Kostadinka Sezanova, Rumiana Gergulova, Pavletta Shestakova and Diana Rabadjieva
Biomimetics 2024, 9(8), 455; https://doi.org/10.3390/biomimetics9080455 - 25 Jul 2024
Viewed by 892
Abstract
Simulated body fluid (SBF) and artificial saliva (AS) are used in biomedical and dental research to mimic the physiological conditions of the human body. In this study, the biomimetic precipitation of double-doped amorphous calcium phosphate in SBF and AS are compared by thermodynamic [...] Read more.
Simulated body fluid (SBF) and artificial saliva (AS) are used in biomedical and dental research to mimic the physiological conditions of the human body. In this study, the biomimetic precipitation of double-doped amorphous calcium phosphate in SBF and AS are compared by thermodynamic modelling of chemical equilibrium in the SBF/AS-CaCl2-MgCl2-ZnCl2-K2HPO4-H2O and SBF/AS-CaCl2-MgCl2-ZnCl2-K2HPO4-Glycine/Valine-H2O systems. The saturation indices (SIs) of possible precipitate solid phases at pH 6.5, close to pH of AS, pH 7.5, close to pH of SBF, and pH 8.5, chosen by us based on our previous experimental data, were calculated. The results show possible precipitation of the same salts with almost equal SIs in the two biomimetic environments at the studied pHs. A decrease in the saturation indices of magnesium and zinc phosphates in the presence of glycine is a prerequisite for reducing their concentrations in the precipitates. Experimental studies confirmed the thermodynamic predictions. Only X-ray amorphous calcium phosphate with incorporated Mg (5.86–8.85 mol%) and Zn (0.71–2.84 mol%) was obtained in the experimental studies, irrespective of biomimetic media and synthesis route. Solid-state nuclear magnetic resonance (NMR) analysis showed that the synthesis route affects the degree of structural disorder of the precipitates. The lowest concentration of dopant ions was obtained in the presence of glycine. Further, the behaviour of the selected amorphous phase in artificial saliva was studied. The dynamic of Ca2+, Mg2+, and Zn2+ ions between the solid and liquid phases was monitored. Both direct excitation 31P NMR spectra and 1H-31P CP-MAS spectra proved the increase in the nanocrystalline hydroxyapatite phase upon increasing the incubation time in AS, which is more pronounced in samples with lower additives. The effect of the initial concentration of doped ions on the solid phase transformation was assessed by solid-state NMR. Full article
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<p>Calculated saturation indices (SIs) of the possible precipitated salts in the biomimetic systems with the participation of SBF (<b>a</b>) and AS (<b>b</b>) at pH 6.5, 7.5, and 8.5. (am) denotes amorphous phase; (do) denotes disordered phase; Gly denotes participation of glycine in the initial solutions; and Val denotes participation of valine in the initial solutions.</p>
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<p>X-ray powder pattern of the sample obtained in Series B in the presence of AS and valine (<b>a</b>,<b>b</b>) direct excitation <sup>31</sup>P NMR spectra of CP-AScp (black), CP-ASf (red), and CP-ASgb (blue) samples.</p>
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<p>Kinetic curves of Mg<sup>2+</sup>, Zn<sup>2+</sup>, and Ca<sup>2+</sup> contents in liquid (<b>a</b>–<b>c</b>) and solid (<b>d</b>–<b>f</b>) phases after different contact times in AS.</p>
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<p>Direct excitation <sup>31</sup>P NMR spectra of CaP-SBFgbGly and CaP-SBFgb samples incubated at different periods in AS: parent samples (black), 1 h in AS (red), 4 h in AS (blue), 24 h in AS (magenta), and 30 days in AS (green).</p>
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<p>Direct excitation <sup>31</sup>P NMR spectra of the samples CaP-SBFgbGly-30 days and CaP-SBFgb-30 days incubated in AS for 30 days. The experimental spectra are in black, while the simulated spectra are in red lines. The deconvoluted <sup>31</sup>P spectra show the individual contributions of the two components, indicating the presence of crystalline (blue) and disordered amorphous phase (green).</p>
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<p><sup>1</sup>H NMR spectra of CaP-SBFgbGly and CaP-SBFgb samples incubated at different periods in AS: parent samples (black), 1 h in AS (red), 4 h in AS (blue), 24 h in AS (magenta), and 30 days in AS (green). The vertical dotted line indicates the increase in the characteristic resonance of the nanocrystalline HAp phase with increased incubation time.</p>
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<p><sup>1</sup>H-<sup>31</sup>P CP-MAS spectra of the samples CaP-SBFgbGly-30 days and CaP-SBFgb-30 days at three different mixing times of 200 µs (black), 1000 µs (blue), and 6000 µs (red).</p>
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<p>pHs and calculated saturated indices (SIs) of CaHPO<sub>4</sub>.2H<sub>2</sub>O, Ca<sub>3</sub>(PO<sub>4</sub>)<sub>2</sub>(am), Ca<sub>8</sub>H<sub>2</sub>(PO<sub>4</sub>)<sub>6</sub>.5H<sub>2</sub>O, and Ca<sub>10</sub>(PO<sub>4</sub>)<sub>6</sub>(OH)<sub>2</sub> in the liquid phase during the maturation of CP-SBFgb (<b>a</b>) and CP-SBFgbGly (<b>b</b>).</p>
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19 pages, 2913 KiB  
Article
Long-Term Performance Evaluation and Fouling Characterization of a Full-Scale Brackish Water Reverse Osmosis Desalination Plant
by Sabrine Chebil, A. Ruiz-García, Soumaya Farhat and Mahmoud Bali
Water 2024, 16(13), 1892; https://doi.org/10.3390/w16131892 - 1 Jul 2024
Viewed by 1016
Abstract
Water scarcity in Tunisia’s semi-arid regions necessitates advanced brackish water desalination solutions. This study evaluates the long-term performance and fouling characteristics of the largest brackish water reverse osmosis desalination plant in southern Tunisia over a period of 5026 days. The plant employs two-stage [...] Read more.
Water scarcity in Tunisia’s semi-arid regions necessitates advanced brackish water desalination solutions. This study evaluates the long-term performance and fouling characteristics of the largest brackish water reverse osmosis desalination plant in southern Tunisia over a period of 5026 days. The plant employs two-stage spiral-wound membrane elements to treat groundwater with a salinity of 3.2 g L−1. The pre-treatment process includes oxidation, sand filtration, and cartridge filtration, along with polyphosphonate antiscalant dosing. Membrane performance was assessed through the analysis of operational data, standardization of permeate flow (Qps) and salt passage (SPs), and the calculation of water (A), solute (B), and ionic (Bj) permeability coefficients. Over the operational period, there was an increase in operating pressure, pressure drop, and permeate conductivity, accompanied by a gradual increase in SPs as well as in the solute B and ionic Bj permeability coefficients. The average B increased by 82%, reflecting a decrease in solute rejection over time. Additionally, the ionic permeability coefficients for both SO42− and Cl ions increased, with Cl showing an 88% increase and SO42− showing an 87% increase. The produced water’s salinity increased by 67%, indicating a significant loss of membrane performance. To identify the cause of these problems, membrane characterization was analyzed using visual inspection, X-ray fluorescence (XRF), and Fourier transform infrared spectroscopy (FTIR). The characterization revealed the complex nature of the foulants, with a predominant presence of calcium sulfate, along with minor quantities of calcite, dolomite, and silica. The extent of CaSO4 deposition suggests poor antiscaling efficiency, highlighting the critical importance of selecting an effective antiscalant to mitigate membrane fouling. Full article
(This article belongs to the Topic Membrane Separation Technology Research)
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<p>BWRO desalination plant.</p>
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<p>Process diagram of the BWRO desalination plant.</p>
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<p>Reverse osmosis membrane cut out for autopsy tests.</p>
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<p>Evolution of operating data over time. (<b>a</b>) Feed pressure over time; (<b>b</b>) Pressure drop over time; (<b>c</b>) Conversion rate over time; (<b>d</b>) Permeate flow over time; (<b>e</b>) Permeate conductivity over time; (<b>f</b>) Specific energy consumption.</p>
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<p>Standardization of operating data. (<b>a</b>) Standardization of permeate flow; (<b>b</b>) Standardization of salt passage.</p>
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<p>Evolution of permeability coefficients. (<b>a</b>) Water permeability coefficient; (<b>b</b>) Solute permeability coefficient; (<b>c</b>) Sulfate ion permeability coefficient; (<b>d)</b> Chloride ion permeability coefficient.</p>
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<p>Fouling characterization. (<b>a</b>) Visual inspection of membrane fouling; (<b>b</b>) X-ray diffraction spectra of deposit sample; (<b>c</b>) IR spectra of deposit sample.</p>
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18 pages, 11348 KiB  
Article
Influence of Amino Acids on Calcium Oxalate Precipitation in Systems of Different Chemical Complexity
by Anamarija Stanković, Nives Matijaković Mlinarić, Jasminka Kontrec, Branka Njegić Džakula, Daniel M. Lyons, Berislav Marković and Damir Kralj
Crystals 2024, 14(7), 599; https://doi.org/10.3390/cryst14070599 - 28 Jun 2024
Viewed by 875
Abstract
The mechanisms and conditions under which urinary stones, pathological biominerals in the kidneys and bladder, are formed have not yet been fully clarified. This study aims to understand the role of the system complexity and seven different amino acids (alanine, phenylalanine, glycine, serine, [...] Read more.
The mechanisms and conditions under which urinary stones, pathological biominerals in the kidneys and bladder, are formed have not yet been fully clarified. This study aims to understand the role of the system complexity and seven different amino acids (alanine, phenylalanine, glycine, serine, cysteine, histidine, and aspartic acid) in the spontaneous precipitation of calcium oxalate. To elucidate these effects, the conditions simulating hyperoxaluria (ci(Ca2+) = 7.5 mmol dm−3 and ci(C2O42−) = 6.0 mmol dm−3) were used for the first time. In this work, systematic research on calcium oxalate precipitation was performed in three systems of different chemical complexities: (a) only calcium and oxalate ions, (b) increased ionic strength, and (c) artificial urine at two initial pHs (pHi = 5.0 and 9.0). In all the investigated systems, the dominant precipitation of calcium oxalate monohydrate (COM) was observed, except in the artificial urine system at pHi = 9.0, in which a mixture of COM and calcium oxalate dihydrate (COD) was obtained. In all the investigated systems, a significant influence of the selected amino acids on the morphology and crystal growth of COM was observed, with more pronounced changes at pHi = 9.0. Overall, polar amino acids and nonpolar phenylalanine inhibit the growth of COM, which is a more pathogenic hydrate form. The artificial urine system proved to be more relevant for the observation of effects relevant to kidney stone formation in the human body. Full article
(This article belongs to the Special Issue Pathological Biomineralization: Recent Advances and Perspectives)
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<p>(<b>A</b>) IR spectra and (<b>B</b>) PXRD diffractograms of samples precipitated in a simple system at pH<sub>i</sub> = 5.0 and pH<sub>i</sub> = 9.0 with the addition of AAs. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid.</p>
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<p>(<b>A</b>) IR spectra and (<b>B</b>) PXRD diffractograms of samples precipitated in the NaCl system at pH<sub>i</sub> = 5 and pH<sub>i</sub> = 9 with the addition of AAs. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid.</p>
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<p>(<b>A</b>) IR spectra and (<b>B</b>) PXRD diffractograms of samples precipitated in the artificial urine system at pH<sub>i</sub> = 5.0 and pH<sub>i</sub> = 9.0 with the addition of AAs. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid.</p>
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<p>The content (<span class="html-italic">w</span>t/%) of precipitated COM in artificial urine containing different AAs and at pH<sub>i</sub> = 9.0. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid.</p>
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<p>Influence of AAs on the crystallite size of COM in different systems. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid. (<b>A</b>) Simple System (<b>B</b>) NaCl System (<b>C</b>) Artificial Urine System.</p>
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<p>Light microscope and SEM images of calcium oxalate samples in a simple system with AAs at pH<sub>i</sub> = 5.0 and pH<sub>i</sub> = 9.0. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid.</p>
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<p>SEM images of calcium oxalate samples precipitated in the NaCl system with the addition of different AAs at pH<sub>i</sub> = 5.0 and pH<sub>i</sub> = 9.0. Yellow and white arrows mark COM of different habitus. Orange arrows show a dendritic structure. Pink arrows show growth in COM and green arrows aggregation. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid.</p>
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<p>SEM images of calcium oxalate samples precipitated in artificial urine with the addition of different AAs at pH<sub>i</sub> = 5.0 and pH<sub>i</sub> = 9.0. Blue arrows show COD crystals, while yellow and white arrows show COM particles of different habitus. The orange arrow displays an aggregate plate structure. Pink arrows show growth in COM and green arrows aggregation. MS—model system, Gly—glycine, Ala—alanine, Phe—phenylalanine, His—histidine, Cys—cysteine, Ser—serine, Asp—aspartic acid.</p>
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