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Keywords = chloride ion transport

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17 pages, 3329 KiB  
Article
Mechanistic Insights into Corrosion and Protective Coating Performance of X80 Pipeline Steel in Xinjiang’s Cyclic Freeze–Thaw Saline Soil Environments
by Gang Cheng, Yuqi Wang, Yiming Dai, Shiyi Zhang, Bin Wei, Chang Xiao and Xian Zhang
Coatings 2025, 15(8), 881; https://doi.org/10.3390/coatings15080881 - 28 Jul 2025
Viewed by 464
Abstract
This study systematically investigated the corrosion evolution and protective mechanisms of X80 pipeline steel in Xinjiang’s saline soil environments under freeze–thaw cycling conditions. Combining regional soil characterization with laboratory-constructed corrosion systems, we employed electrochemical impedance spectroscopy, potentiodynamic polarization, and surface analytical techniques to [...] Read more.
This study systematically investigated the corrosion evolution and protective mechanisms of X80 pipeline steel in Xinjiang’s saline soil environments under freeze–thaw cycling conditions. Combining regional soil characterization with laboratory-constructed corrosion systems, we employed electrochemical impedance spectroscopy, potentiodynamic polarization, and surface analytical techniques to quantify temporal–spatial corrosion behavior across 30 freeze–thaw cycles. Experimental results revealed a distinctive corrosion resistance pattern: initial improvement (cycles 1–10) attributed to protective oxide layer formation, followed by accelerated degradation (cycles 10–30) due to microcrack propagation and chloride accumulation. Synchrotron X-ray diffraction analyses identified sulfate–chloride ion synergism as the primary driver of localized corrosion disparities in heterogeneous soil matrices. A comparative evaluation of asphalt-coated specimens demonstrated a 62%–89% corrosion rate reduction, with effectiveness directly correlating with coating integrity and thickness (200–500 μm range). Molecular dynamics simulations using Materials Studio revealed atomic-scale ion transport dynamics at coating–substrate interfaces, showing preferential Cl permeation through coating defects. These multiscale findings establish quantitative relationships between environmental stressors, coating parameters, and corrosion kinetics, providing a mechanistic framework for optimizing protective coatings in cold-region pipeline applications. Full article
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20 pages, 2847 KiB  
Article
Oxidative Stress Disrupts Gill Function in Eriocheir sinensis: Consequences for Ion Transport, Apoptosis, and Autophagy
by Wenrong Feng, Qinghong He, Qiqin Yang, Yuanfeng Xu, Gang Jiang, Jianlin Li, Jun Zhou, Rui Jia and Yongkai Tang
Antioxidants 2025, 14(8), 897; https://doi.org/10.3390/antiox14080897 - 22 Jul 2025
Viewed by 339
Abstract
Oxidative stress is a key mediator of physiological dysfunction in aquatic organisms under environmental challenges, yet its comprehensive impacts on gill physiology require further clarification. This study investigated the molecular and cellular responses of Eriocheir sinensis gills to hydrogen peroxide (H2O [...] Read more.
Oxidative stress is a key mediator of physiological dysfunction in aquatic organisms under environmental challenges, yet its comprehensive impacts on gill physiology require further clarification. This study investigated the molecular and cellular responses of Eriocheir sinensis gills to hydrogen peroxide (H2O2)-induced oxidative stress, integrating antioxidant defense, ion transport regulation, and stress-induced cell apoptosis and autophagy. Morphological alterations in the gill filaments were observed, characterized by septum degeneration, accumulation of haemolymph cells, and pronounced swelling. For antioxidant enzymes like catalase (CAT) and glutathione peroxidase (GPx), activities were enhanced, while superoxide dismutase (SOD) activity was reduced following 48 h of exposure. Overall, the total antioxidant capacity (T-AOC) showed a significant increase. The elevated concentrations of malondialdehyde (MDA) and H2O2 indicated oxidative stress. Ion transport genes displayed distinct transcription patterns: Na+-K+-2Cl co-transporter-1 (NKCC1), Na+/H+ exchanger 3 (NHE3), aquaporin 7 (AQP7), and chloride channel protein 2 (CLC2) were significantly upregulated; the α-subunit of Na+/K+-ATPase (NKAα) and carbonic anhydrase (CA) displayed an initial increase followed by decline; whereas vacuolar-type ATPase (VATP) consistently decreased, suggesting compensatory mechanisms to maintain osmotic balance. Concurrently, H2O2 triggered apoptosis (Bcl2, Caspase-3/8) and autophagy (beclin-1, ATG7), likely mediated by MAPK and AMPK signaling pathways. These findings reveal a coordinated yet adaptive response of crab gills to oxidative stress, providing new insights into the mechanistic basis of environmental stress tolerance in crustaceans. Full article
(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—2nd Edition)
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14 pages, 1518 KiB  
Article
Synthesis of Multifunctional Hyperbranched Polymers via Atom Transfer Radical Self-Condensing Vinyl Polymerization for Applications in Polyurethane-Based Anion Exchange Membranes
by Nhat Hong Nguyen, Chih-Feng Huang and Tongsai Jamnongkan
Polymers 2025, 17(14), 1930; https://doi.org/10.3390/polym17141930 - 13 Jul 2025
Viewed by 408
Abstract
Anion exchange membranes (AEMs) are vital for electrochemical energy devices such as alkaline fuel cells and water electrolyzers, enabling the use of non-precious metal catalysts despite challenges from alkaline degradation. Hyperbranched polymers (hbPs) with their globular structure, high functional group density, and simple [...] Read more.
Anion exchange membranes (AEMs) are vital for electrochemical energy devices such as alkaline fuel cells and water electrolyzers, enabling the use of non-precious metal catalysts despite challenges from alkaline degradation. Hyperbranched polymers (hbPs) with their globular structure, high functional group density, and simple synthesis, offer a promising platform for enhancing transport and stability. In this study, multifunctional hbPs were synthesized from 4-vinylbenzyl chloride (VBC) and 2-hydroxyethyl methacrylate (HEMA) via atom transfer radical self-condensing vinyl polymerization (ATR-SCVP) and crosslinked into polyurethane-based AEMs. Characterization confirmed successful copolymerization and crosslinking, with excellent alkaline stability. Membranes crosslinked with higher molecular weight (MW) and VBC-richer hbPs (e.g., OH-hbP1-PU) exhibited high water uptake (75%) but low ion-exchange capacity (1.54 mmol/g) and conductivity (186 µS/cm), attributed to steric hindrance and insufficient ionic network connectivity. In contrast, OH-hbP2-PU exhibited optimal properties, with the highest OH conductivity (338 µS/cm) and IEC (2.64 mmol/g), highlighting a balanced structure for efficient ion transport. This work offers a tunable strategy for high-performance AEM development through tailored hbP architecture. Full article
(This article belongs to the Special Issue Development and Innovation of Stimuli-Responsive Polymers)
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23 pages, 2433 KiB  
Review
Massive Activation of GABAA Receptors: Rundown, Ionic and Neurodegenerative Consequences
by Sergey A. Menzikov, Danila M. Zaichenko, Aleksey A. Moskovtsev, Sergey G. Morozov and Aslan A. Kubatiev
Biomolecules 2025, 15(7), 1003; https://doi.org/10.3390/biom15071003 - 13 Jul 2025
Viewed by 468
Abstract
The GABAA receptors, through a short-term interaction with a mediator, induce hyperpolarization of the membrane potential (Vm) via the passive influx of chloride ions (Cl) into neurons. The massive (or intense) activation of the GABAARs [...] Read more.
The GABAA receptors, through a short-term interaction with a mediator, induce hyperpolarization of the membrane potential (Vm) via the passive influx of chloride ions (Cl) into neurons. The massive (or intense) activation of the GABAARs by the agonist could potentially lead to depolarization/excitation of the Vm. Although the ionic mechanisms of GABAA-mediated depolarization remain incompletely understood, a combination of the outward chloride current and the inward bicarbonate current and the resulting pH shift are the main reasons for this event. The GABAA responses are determined by the ionic gradients—neuronal pH/bicarbonate homeostasis is maintained by carbonic anhydrase and electroneutral/electrogenic bicarbonate transporters and the chloride level is maintained by secondary active cation–chloride cotransporters. Massive activation can also induce the rundown effect of the receptor function. This rundown effect partly involves phosphorylation, Ca2+ and the processes of receptor desensitization. In addition, by various methods (including fluorescence and optical genetic methods), it has been shown that massive activation of GABAARs during pathophysiological activity is also associated with an increase in [Cl]i and a decline in the pH and ATP levels in neurons. Although the relationship between the neuronal changes induced by massive activation of GABAergic signaling and the risk of developing neurodegenerative disease has been extensively studied, the molecular determinants of this process remain somewhat mysterious. The aim of this review is to summarize the data on the relationship between the massive activation of inhibitory signaling and the ionic changes in neurons. The potential role of receptor dysfunction during massive activation and the resulting ionic and metabolic disruption in neurons during the manifestation of network/seizure activity will be considered. Full article
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15 pages, 887 KiB  
Article
Mapping Ammonium Flux Across Bacterial Porins: A Novel Electrophysiological Assay with Antimicrobial Relevance
by Ishan Ghai
Appl. Sci. 2025, 15(14), 7677; https://doi.org/10.3390/app15147677 - 9 Jul 2025
Viewed by 232
Abstract
This study presents a quantitative electrophysiological method to directly measure the passive transport of ammonium ions through bacterial outer membrane porins. Using a zero-current reversal potential assay in planar lipid bilayers under defined bi-ionic gradients, this study evaluates the permeability of ammonium salts [...] Read more.
This study presents a quantitative electrophysiological method to directly measure the passive transport of ammonium ions through bacterial outer membrane porins. Using a zero-current reversal potential assay in planar lipid bilayers under defined bi-ionic gradients, this study evaluates the permeability of ammonium salts through two general diffusion porins: Omp-Pst2 from Providencia stuartii and OmpF from Escherichia coli. Under matched ionic conditions, Omp-Pst2 exhibited significantly higher ammonium flux—approximately 6000 ions per second per monomer at a 1 µM gradient—compared to ~4000 ions per second for OmpF. Importantly, the identity of the accompanying anion (chloride vs. sulfate) modulated both the ion selectivity and flux rate, highlighting the influence of counterion interactions on porin-mediated transport. These findings underscore how structural differences between porins—such as pore geometry and charge distribution—govern ion permeability. The method applied here provides a robust framework for quantifying nutrient flux at the single-channel level and offers novel insights into how Gram-negative bacteria may adapt their membrane transport mechanisms under nitrogen-limited conditions. This work not only enhances our understanding of outer membrane permeability to small ions like ammonium, but also has implications for antimicrobial strategy development and biotechnological applications in nitrogen assimilation. Full article
(This article belongs to the Special Issue Innovative Digital Health Technologies and Their Applications)
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12 pages, 2267 KiB  
Article
Composite Polymer Electrolytes with Tailored Ion-Conductive Networks for High-Performance Sodium-Ion Batteries
by Caizhen Yang, Zongyou Li, Qiyao Yu and Jianguo Zhang
Materials 2025, 18(13), 3106; https://doi.org/10.3390/ma18133106 - 1 Jul 2025
Viewed by 328
Abstract
Gel-polymer electrolytes offer a promising route toward safer and more stable sodium-ion batteries, but conventional polymer systems often suffer from low ionic conductivity and limited voltage stability. In this study, we developed composite GPEs by embedding methylammonium lead chloride (CH3NH3 [...] Read more.
Gel-polymer electrolytes offer a promising route toward safer and more stable sodium-ion batteries, but conventional polymer systems often suffer from low ionic conductivity and limited voltage stability. In this study, we developed composite GPEs by embedding methylammonium lead chloride (CH3NH3PbCl3, MPCl) into a UV-crosslinked ethoxylated trimethylolpropane triacrylate (ETPTA) matrix, with sodium alginate (SA) as an ionic conduction enhancer. Three types of membranes—GPE-P, GPE-El, and GPE-Eh—were synthesized and systematically compared. Among them, the high-MPCl formulation (GPE-Eh) exhibited the best performance, achieving a high ionic conductivity of 2.14 × 10−3 S·cm−1, a sodium-ion transference number of 0.66, and a wide electrochemical window of approximately 4.9 V vs. Na+/Na. In symmetric Na|GPE|Na cells, GPE-Eh enabled stable sodium plating/stripping for over 600 h with low polarization. In Na|GPE|NVP cells, it delivered a high capacity retention of ~79% after 500 cycles and recovered ~89% of its initial capacity after high-rate cycling. These findings demonstrate that the perovskite–polymer composite structure significantly improves ion transport, interfacial stability, and electrochemical durability, offering a viable path for the development of next-generation quasi-solid-state sodium-ion batteries. Full article
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13 pages, 11396 KiB  
Article
Morphometric and Enzymatic Changes in Gills of Rainbow Trout After Exposure to Suboptimal Low Temperature
by Elias Lahnsteiner, Nooshin Zamannejad, Anna Dünser and Franz Lahnsteiner
Curr. Issues Mol. Biol. 2025, 47(6), 457; https://doi.org/10.3390/cimb47060457 - 13 Jun 2025
Viewed by 867
Abstract
The present study investigated the influence of a 30 day exposure of rainbow trout (Oncorhynchus mykiss) to a suboptimal low temperature of 1.8 ± 1.0 °C on their different gill characteristics (morphometry, enzyme activities, and expression of genes) in comparison to [...] Read more.
The present study investigated the influence of a 30 day exposure of rainbow trout (Oncorhynchus mykiss) to a suboptimal low temperature of 1.8 ± 1.0 °C on their different gill characteristics (morphometry, enzyme activities, and expression of genes) in comparison to fish acclimated to 9.4 ± 0.1 °C. Morphometric analysis revealed a significant decrease in the distance between the secondary lamellae at the low temperature, which can be interpreted as a decrease in the effective gill surface. The epithelial thickness increased at the lower temperatures, which is considered a mechanism to reduce ion fluxes and save the energy costs for osmoregulation. The length of the primary lamellae, distance between the primary lamellae, length of the secondary lamellae, as well as the number of mucus cells, chloride cells, and capillaries per mm of the secondary lamella were similar between the temperature regimes. The enzymatic activities of pyruvate kinase and malate dehydrogenase were significantly increased in cold-exposed fish, whereas lactate dehydrogenase activity was higher in controls, indicating increased energy expenditure and adjustments in energy metabolism. The activities of carbonic anhydrase, caspase, Na+/K+ ATPase, and H+ ATPase, and the gene expressions of hif1a, ca2, rhCG, slc26a6, and slc9a1 showed no statistically significant differences between the two temperature regimes. Therefore, it can be concluded that ammonia transport, acid–base regulation, and osmoregulation were not affected by the tested low temperature regime. These findings highlight that exposure to suboptimal temperatures induces structural and metabolic modifications in rainbow trout gills, potentially as an adaptive response to thermal stress. This study contributes to the understanding of fish acclimation to cold environments, with implications for aquaculture and ecological resilience in changing climates. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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19 pages, 2797 KiB  
Review
A Review of the Calcium Sulphoaluminate Cement Mixed with Seawater: Hydration Process, Microstructure, and Durability
by Han Li, Jing Meng, Yang Liu, Lilin Yang, Yukai Wang, Ning Xie, Jinping Ou and Guoxiang Zhou
J. Mar. Sci. Eng. 2025, 13(6), 1076; https://doi.org/10.3390/jmse13061076 - 29 May 2025
Cited by 1 | Viewed by 813
Abstract
The preparation of low-cost and high-durability cement-based material systems using seawater mixing has become an urgent task in marine engineering construction. The requirements have addressed key challenges, including high transportation costs for fresh water and raw materials, poor structural durability, and difficulty in [...] Read more.
The preparation of low-cost and high-durability cement-based material systems using seawater mixing has become an urgent task in marine engineering construction. The requirements have addressed key challenges, including high transportation costs for fresh water and raw materials, poor structural durability, and difficulty in meeting actual construction schedules. Sulfatealuminate cement (CSA) has become an ideal material for marine engineering due to its high corrosion resistance, rapid early strength, which is 35–40 MPa of 3-day compressive strength and is 1.5–2 times compared ordinary Portland cement (OPC), and low-carbon characteristics, reduced production energy consumption by 35–50%, and CO2 emissions of 0.35–0.45 tons/ton. The Cl and SO42− in seawater can accelerate the hydration of CSA, promote the formation of ettringite (AFt), and generate Friedel’s salt fixed chloride ions, significantly enhancing its resistance to chloride corrosion. Its low alkalinity (pH ≈ 10.6) and dense structure further optimize its resistance to sulfate corrosion. In terms of environmental benefits, CSA-mixed seawater can save 15–20% fresh water. And the use of solid waste preparation can reduce environmental burden by 38.62%. In the future, it is necessary to combine multi-scale simulation to predict long-term performance, develop self-healing materials and intelligent control technologies, and promote their large-scale application in sustainable marine infrastructure. Full article
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22 pages, 3210 KiB  
Article
Development and Validation of a Coupled Hygro-Chemical and Thermal Transport Model in Concrete Using Parallel FEM
by Okpin Na and Giyeol Lee
Appl. Sci. 2025, 15(11), 5989; https://doi.org/10.3390/app15115989 - 26 May 2025
Viewed by 379
Abstract
The durability of reinforced concrete structures in aggressive environments is strongly influenced by the ingress of chloride and other harmful ions, which is further complicated under partially saturated conditions, due to the coexistence of liquid and gas phases within the pore network. This [...] Read more.
The durability of reinforced concrete structures in aggressive environments is strongly influenced by the ingress of chloride and other harmful ions, which is further complicated under partially saturated conditions, due to the coexistence of liquid and gas phases within the pore network. This study aimed to develop a predictive moisture–chemical–temperature model and to elucidate the mechanisms governing ion transport in partially saturated concrete. A multi-species hygro-chemo-thermo transport model was formulated based on the Nernst–Planck equation, incorporating electroneutrality, zero current conditions, and the coupled effects of moisture and temperature gradients. The model was numerically implemented using a parallel FE method with the Crank–Nicolson scheme, supported by domain decomposition and SPMD techniques for high computational efficiency. As a result, experimental validation was performed through chloride ponding tests under varying temperature conditions (20 °C, 35 °C, 50 °C), water-to-cement ratios (0.55, 0.65), and relative humidity differences (100%, 60%). The simulation results showed good agreement with the experimental data and confirmed that the proposed model can effectively predict chloride penetration under both isothermal and non-isothermal conditions. Additionally, the simulations revealed that moisture gradients accelerate ion transport, as the inward migration of the moisture front enhances the diffusion rates of chloride, sodium, and calcium ions until a steady-state moisture distribution is reached. Full article
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16 pages, 6537 KiB  
Article
The Impact of Stray Currents on Chloride Transport in the Concrete of Urban Rail Transit Structures
by Yuancheng Ni, Eryu Zhu and Liangjiang Chen
Buildings 2025, 15(10), 1695; https://doi.org/10.3390/buildings15101695 - 17 May 2025
Viewed by 342
Abstract
To study the chloride transport properties of urban rail transit structures under the action of stray currents, electrochemical tests were employed as part of this paper to investigate the impact of stray currents on cementitious materials and pore structure and further analyze the [...] Read more.
To study the chloride transport properties of urban rail transit structures under the action of stray currents, electrochemical tests were employed as part of this paper to investigate the impact of stray currents on cementitious materials and pore structure and further analyze the chloride distribution of specimens in different conditions. Results show that a stray current accelerates calcium ion precipitation in chloride solutions, reducing calcium hydroxide content compared to unelectrified specimens. This dissolution alters the concrete pore structure, increasing porosity by 26.3%, 31.2%, and 36.1% for specimens electrified at 50 mA, 100 mA, and 150 mA, respectively, after 28 days. The effect coefficient kp of stray currents on the porosity of concrete is given with the test results. Electrified specimens have a higher chloride content compared to unelectrified specimens, with free chloride increasing more than bound chloride as current and time increase. The chloride ion binding capacity of concrete electrified at 150 mA is only 60% that of unelectrified, indicating the significant weakening effect of stray currents on it. Full article
(This article belongs to the Section Building Materials, and Repair & Renovation)
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13 pages, 463 KiB  
Article
Cryoconservation Modifies Ion Transport Pathways in the Skin Microenvironment: An In Vitro Study
by Iga Hołyńska-Iwan, Marcin Wróblewski, Lucyna Kałużna, Tomasz Dziaman, Jolanta Czuczejko, Olga Zavyalova, Dorota Olszewska-Słonina and Karolina Szewczyk-Golec
Processes 2025, 13(5), 1493; https://doi.org/10.3390/pr13051493 - 13 May 2025
Viewed by 307
Abstract
Due to the lack of skin donors, the short time frame for conducting the procedure, and the increasing demand for tissue specimens, the proper storage conditions for skin fragments have gained critical importance. Therefore, the search for methods for storing skin tissue long-term, [...] Read more.
Due to the lack of skin donors, the short time frame for conducting the procedure, and the increasing demand for tissue specimens, the proper storage conditions for skin fragments have gained critical importance. Therefore, the search for methods for storing skin tissue long-term, ensuring its physiological functions, is a matter of considerable interest. Freezing skin fragments in a cryoprotectant solution, such as dimethylsulfoxide (DMSO), can be a valuable complement to tissues for transplantation and for supplying difficult-to-heal wounds. This study aimed to assess the effect of deep freezing rabbit skin fragments immersed in a 5% DMSO solution on their electrophysiological parameters. Control (n = 23) and defrosted skin specimens were incubated in Ringer (n = 21), amiloride (n = 26), and bumetanide (n = 24) solutions. Then, resistance (R), potential difference (PD), and minimal and maximal PD were measured. The specimens did not show differences in R values compared to controls, which means that the skin subjected to freezing was compact and durable. However, the tissue subjected to freezing in DMSO solution presented increased transport of sodium and chloride ions, which may translate into a change in pain perception, the development of hypersensitivity and/or allergy, and the initiation of repair and regeneration processes. Full article
(This article belongs to the Special Issue Structure Optimization and Transport Characteristics of Porous Media)
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17 pages, 3066 KiB  
Article
Polymer Inclusion Membranes Based on Sulfonic Acid Derivatives as Ion Carriers for Selective Separation of Pb(II) Ions
by Cezary Kozlowski and Iwona Zawierucha
Membranes 2025, 15(5), 146; https://doi.org/10.3390/membranes15050146 - 12 May 2025
Viewed by 775
Abstract
In this paper, polymer inclusion membranes (PIMs) were created using poly(vinyl chloride)-based alkyl sulfonic acid derivatives as ion carriers and dioctyl terephthalate as a plasticizer for the selective separation of Pb(II), Cu(II), and Cd(II) ions from aqueous nitrate solutions. The ion carriers were [...] Read more.
In this paper, polymer inclusion membranes (PIMs) were created using poly(vinyl chloride)-based alkyl sulfonic acid derivatives as ion carriers and dioctyl terephthalate as a plasticizer for the selective separation of Pb(II), Cu(II), and Cd(II) ions from aqueous nitrate solutions. The ion carriers were dinonylnaphthalenesulfonic acid (DNNSA) and nonylbenzenesulfonic acid (NBSA). The influence of the carrier and the plasticizer concentration in the membrane on the transport efficiency was investigated. For the PIM system, 15% wt. of carrier (DNNSA, NBSA), 20% wt. of plasticizer, and 65% wt. of polymer poly(vinyl chloride) PVC were the optimal proportions, with which the process was the most effective. Research on the transport kinetics has shown that the transport of Pb(II) ions through PIMs containing acidic carriers adheres to a first-order kinetics equation, which is characteristic of a facilitated transport mechanism. The activation parameter for these processes suggests that the high performance of these ion carriers is associated with the immobilization of the carrier within the membrane. It was found that PIMs based on DNNSA facilitate the selective separation of Pb(II)/Cu(II) and Pb(II)/Cd(II) mixtures, achieving high separation factors. Full article
(This article belongs to the Special Issue Recent Advances in Polymer Inclusion Membranes)
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22 pages, 9500 KiB  
Article
Increased CO2 Concentration Mitigates the Impact of Nitrite on Zebrafish (Danio rerio) Liver and Gills
by Xinyu Wang, Yao Tang, Hui Yang, Ya He, Kang Ou-Yang, Liangmou Wang, Qian Zhang, Dapeng Li and Li Li
Fishes 2025, 10(5), 205; https://doi.org/10.3390/fishes10050205 - 1 May 2025
Viewed by 474
Abstract
Nitrite and carbon dioxide (CO2) are common environmental substances in intensive aquaculture ponds. However, the effects and mechanisms of their combined exposure on aquatic animals remain unclear. In this study, we investigated the toxic effects of 2.5, 5, and 10 mg/L [...] Read more.
Nitrite and carbon dioxide (CO2) are common environmental substances in intensive aquaculture ponds. However, the effects and mechanisms of their combined exposure on aquatic animals remain unclear. In this study, we investigated the toxic effects of 2.5, 5, and 10 mg/L CO2 in the presence of 2 mg/L nitrite on hematological, blood gas parameters, and liver physiological and pathological changes in zebrafish (Danio rerio) over 14 days and 28 days. Our results demonstrated a reduced nitrite uptake and accumulation in the gills and liver of zebrafish exposed to nitrite and varying levels of CO2. Increased CO2 levels also led to a decrease in the expression of gill ae1, whereas the transcriptional levels of nhe1 and nhe3b, nkcc and nbc1 were notably upregulated. Moreover, there was a decrease in Cl and Na+ concentrations, along with an increase in K+ concentrations. These changes suggested that zebrafish responded to increased CO2 stress by reducing their absorption of chloride-dependent nitrite, excreting H+ and maintaining their internal pH. Exposure to higher CO2 levels in the presence of nitrite resulted in lower blood MetHb levels and liver oxidative stress compared to the nitrite single-exposure treatment. Furthermore, co-treatment with CO2 and nitrite attenuated the nitrite-induced damage to genes related to mitochondrial respiratory chain function (ndufs1, mtnd5, mtycb, atp5f1b, mtatp8), leading to elevated ATP levels. Exposure to nitrite alone increased the expression of lipolytic genes (hsla, cpt1aa, atgl) and decreased the expression of lipid synthesis genes (fasn, acaca), resulting in a decrease in TG and TC content in zebrafish liver. However, co-treatment with CO2 and nitrite prevented the nitrite-induced disruption of lipid metabolism, as evidenced by the improvement in TG and TC levels, as well as transcriptional levels of lipid metabolism-related genes. In conclusion, our study suggests that in the presence of 2 mg/L nitrite, increased CO2 (2.5–10 mg/L) may modulate ion transporter genes to reduce the chloride-dependent nitrite uptake and maintain pH homeostasis, concurrently alleviating oxidative stress, restoring mitochondrial respiratory function, and improving lipid metabolism in a dose-dependent manner. These changes may be related to the increase in the concentration of bicarbonate ions in the water as the CO2 level rises. These findings shed light on the potential protective effects of CO2 in mitigating the harmful effects of nitrite exposure in aquatic animals. Full article
(This article belongs to the Section Physiology and Biochemistry)
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19 pages, 3350 KiB  
Article
A Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Cystic Fibrosis Drugs (Caftors) in Plasma and Its Application for Therapeutic Monitoring
by Valentina D’Atri, Fabrizio Corrado, François Versace, Susana Alves Saldanha, Thomas Mercier, Monia Guidi, Paul Thoueille, Sylvain Blanchon, Angela Koutsokera, Michael Vogeser, Catia Marzolini, François Girardin, Georgia Mitropoulou, Zisis Balmpouzis, Isabelle Rochat, Alain Sauty, Laurent Arthur Decosterd and Eva Choong
Molecules 2025, 30(9), 1866; https://doi.org/10.3390/molecules30091866 - 22 Apr 2025
Viewed by 929
Abstract
Cystic fibrosis (CF) is a life-threatening disorder caused by mutations in the CFTR gene, leading to defective chloride ion transport and thickened mucus in the respiratory and gastrointestinal systems. CFTR modulators, including ivacaftor, lumacaftor, tezacaftor, and elexacaftor, have improved patient outcomes, but interindividual [...] Read more.
Cystic fibrosis (CF) is a life-threatening disorder caused by mutations in the CFTR gene, leading to defective chloride ion transport and thickened mucus in the respiratory and gastrointestinal systems. CFTR modulators, including ivacaftor, lumacaftor, tezacaftor, and elexacaftor, have improved patient outcomes, but interindividual pharmacokinetic variability and potential drug–drug interactions require therapeutic drug monitoring (TDM) for optimal efficacy and safety. In this context, a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous quantification of CFTR modulators and their major active metabolites in human plasma to support pharmacokinetic studies and routine TDM. The multiplex LC-MS/MS assay was established using plasma protein precipitation, followed by chromatographic separation on an Xselect HSS T3 (Waters®) column and positive electrospray ionization mode detection. The method was validated based on FDA and EMA guidelines for specificity, linearity, accuracy (89.8–107.8%), repeatability (1.1–8.1%), intermediate fidelity (1.3–10.9%), matrix effects, and stability, demonstrating a robust performance with excellent precision and accuracy. International interlaboratory comparisons confirmed the reliability of the assay. The developed method can be applied for the clinical monitoring of caftors’ plasma concentrations and preliminary data suggest that it can also be applied to alternative matrices, such as breast milk. This method will serve to characterize caftors’ pharmacokinetic variability and monitor drug–drug interactions to further refine personalized dosing strategies and enhance precision medicine treatments for patients with CF. Full article
(This article belongs to the Special Issue Exclusive Feature Papers in Analytical Chemistry)
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18 pages, 2726 KiB  
Article
TMEM16A Maintains Acrosomal Integrity Through ERK1/2, RhoA, and Actin Cytoskeleton During Capacitation
by Ana L. Roa-Espitia, Tania Reyes-Miguel, Monica L. Salgado-Lucio, Joaquín Cordero-Martínez, Dennis Tafoya-Domínguez and Enrique O. Hernández-González
Int. J. Mol. Sci. 2025, 26(8), 3750; https://doi.org/10.3390/ijms26083750 - 16 Apr 2025
Viewed by 579
Abstract
Mammalian spermatozoa undergo a series of physiological and biochemical changes in the oviduct that lead them to acquire the ability to fertilize eggs. During their transit in the oviduct, spermatozoa face a series of environmental changes that can affect sperm viability. A series [...] Read more.
Mammalian spermatozoa undergo a series of physiological and biochemical changes in the oviduct that lead them to acquire the ability to fertilize eggs. During their transit in the oviduct, spermatozoa face a series of environmental changes that can affect sperm viability. A series of ion channels and transporters, as well as the sperm cytoskeleton, allow spermatozoa to remain viable and functional. Cl channels such as TMEM16A (calcium-activated chloride channel), CFTR (cystic fibrosis transmembrane conductance regulator), and ClC3 (chloride voltage-gated channel 3) are some of the ion transporters involved in maintaining cellular homeostasis. They are expressed in mammalian spermatozoa and are associated with capacitation, acrosomal reaction, and motility. However, little is known about their role in maintaining sperm volume. Therefore, this study aimed to determine the mechanism through which TMEM16A maintains sperm volume during capacitation. The effects of TMEM16A were compared to those of CFTR and ClC3. Spermatozoa were capacitated in the presence of specific TMEM16A, CFTR, and ClC3 inhibitors, and the results showed that only TMEM16A inhibition increased acrosomal volume, leading to changes within the acrosome. Similarly, only TMEM16A inhibition prevented actin polymerization during capacitation. Further analysis showed that TMEM16A inhibition also prevented ERK1/2 and RhoA activation. On the other hand, TMEM16A and CFTR inhibition affected both capacitation and spontaneous acrosomal reaction, whereas ClC3 inhibition only affected the spontaneous acrosomal reaction. In conclusion, during capacitation, TMEM16A activity regulates acrosomal structure through actin polymerization and by regulating ERK1/2 and RhoA activities. Full article
(This article belongs to the Section Biochemistry)
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