Chloride Transport Research Articles

A Review of Chloride Penetration of Recycled Concrete with Enhancement Treatment and Service Life Prediction.

The application of recycled coarse aggregate (RA) in structural concrete can save non-renewable resources and reduce land occupation. Developing comprehensive knowledge of chloride penetration and service life modeling of recycled coarse aggregate concrete (RAC) is a prerequisite for practice. However, compared with the natural aggregate concrete (NAC), the inferior durability performance, especially chloride penetration resistance, of RAC hinders its application in structural concrete. Therefore, many RAC performance enhancement methods have been proposed. This paper presents a holistic review focused on the chloride penetration of RAC with/without enhancement methods and service life prediction. The current RAC performance enhancement methods are introduced. The improvement effect of the corresponding enhancement methods on the chloride penetration resistance of RAC are discussed and analyzed in turn. Based on the reviewed data on the chloride diffusion coefficient, the modification efficiencies of assorted enhancement methods are summarized. With the hope of promoting RAC application in structural concrete, the current literature on chloride-ingress-based service life prediction for RAC is also overviewed. In addition, the typical influencing factors on chloride transport properties are also discussed, i.e., RA quality. It can be concluded that enhancement techniques can effectively improve the chloride penetration resistance of RAC. The old mortar enhancement or removal methods can improve the chloride penetration resistance by 15-30%, depending on the specific treatment measures. The modification efficiency of the modifier material depends on the specific type and content of the incorporated substance, which ranges from approximately 5% to 95%. The estimated service life of RAC structures decreases with the increasing RA replacement ratio. Finally, concluding remarks are provided concerning future research on the chloride transport behavior of RAC.

Numerical modelling on coupled behavior of calcium leaching and chloride transport in cement-based materials by considering ion desorption

Concrete structures serving in water environment with rich chloride ions are subjected to the coupling action of calcium leaching and chloride corrosion. In this paper, a transport model of calcium and chloride ions coupled with the calcium solid-liquid equilibrium equation is proposed to simulate the behavior of calcium leaching and chloride penetration in concrete. In the model, the effect of free chloride ions bound by solid calcium and the release of bound chloride ions caused by the dissolution of solid calcium is considered. Secondly, the model is numerically solved by using the finite difference method of Crank-Nicolson scheme. Then, the experimental data of porosity and calcium silicon ratio, chloride concentration are compared to the calculated results to validate the model. Finally, a numerical simulation is conducted to analyze the evolution of ion concentration, solid calcium content and porosity of cement paste slice exposed to deionized water and accelerated dissolution solution. The results show that, the concentration of calcium ion decreases with corrosion time, while that of chloride ion increases. There are concentration gradient distributions of calcium and chloride ions in the slice. The higher the concentration of accelerated dissolution solution, the larger the porosity of cement paste and the higher the concentration of chloride ions in the paste. It indicates that, the calcium leaching accelerates the chloride penetration into concrete. In addition, the dissolution process of solid calcium, i.e. calcium hydroxide first dissolves followed by C-S-H gel, are presented.

Effect of elexacaftor-tezacaftor-ivacaftor on nasal potential difference and lung function in Phe508del rats.

Introduction: Phe508del is the most common cystic fibrosis transmembrane conductance regulator (CFTR) gene variant that results in the recessive genetic disorder cystic fibrosis (CF). The recent development of highly effective CFTR modulator therapies has led to significant health improvements in individuals with this mutation. While numerous animal models of CF exist, few have a CFTR mutation that is amenable to the triple combination therapy elexacaftor-tezacaftor-ivacaftor (ETI). Methods: To determine the responsiveness of Phe508del rats to ETI, a baseline nasal potential difference was measured. Subsequently, they received ETI daily for 14days, after which post-treatment nasal potential difference, lung mechanics (via flexiVent) and lung ventilation (via X-ray Velocimetry) were assessed. Results: Chloride ion transport in nasal airways was restored in Phe508del rats treated with ETI, but neither lung mechanics nor ventilation were significantly altered. Discussion: These findings validate the usefulness of this rat model for future investigations of modulator therapy in CF.

Microstructure and chloride transport of aeolian sand concrete under long-term natural immersion

Abstract River sand was consumed in large quantities, and alternatives to river sand were urgently needed. There are a large number of natural resources of aeolian sand in western China. Aeolian sand was prepared into aeolian sand concrete (ASC). It can greatly reduce the consumption of river sand and inhibit the process of desertification to protect the environment. ASC is a new type of concrete material prepared by using aeolian sand as fine aggregate. To clarify the chloride ion transport behaviour in the ASC under long-term natural immersion, the aeolian sand was 100% substituted for the river sand to prepare the full ASC with three water–binder ratios. The ASC was naturally immersed in 3 and 6% NaCl solutions for a long time, and nuclear magnetic resonance and microscopic scanning electron microscopy techniques were used. The change rule of chloride ion content at different depths of the ASC was studied, and its microstructure characteristics under different erosion times were analysed. The results showed that the free chloride ion concentration at different depths of the ASC increased with increasing water–binder ratio, immersion time, and chloride concentration. After soaking in the salt solution, the hydration products in the ASC reacted with chloride ions to form Friedel salt, which filled the internal pores and microcracks of the ASC, improved its interface transition zone structure, and increased the compactness of the test piece. The porosity of the three groups of ASC with different water–binder ratios decreased by 0.95, 1.03, and 1.15% after soaking in 6% salt solution for 12 m. To study the diffusion law of chloride ions in ASC, combined with influencing factors such as temperature, humidity, D value, deterioration effect and chloride ion combination, Fick’s second law was modified, and a chloride ion diffusion model of ASC with high accuracy was established, with a fitting correlation number above 0.93, which provided a reference for the research and application of ASC in saline areas.

CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants

BackgroundMany affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. MethodsNext-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). ResultsOf 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. ConclusionsCFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.

Naphthalene Diimide-Based Metallacage as an Artificial Ion Channel for Chloride Ion Transport.

Developing synthetic molecular devices for controlling ion transmembrane transport is a promising research field in supramolecular chemistry. These artificial ion channels provide models to study ion channel diseases and have huge potential for therapeutic applications. Compared with self-assembled ion channels constructed by intermolecular weak interactions between smaller molecules or cyclic compounds, metallacage-based ion channels have well-defined structures and can exist as single components in the phospholipid bilayer. A naphthalene diimide-based artificial chloride ion channel is constructed through efficient subcomponent self-assembly and its selective ion transport activity in large unilamellar vesicles and the planar lipid bilayer membrane by fluorescence and ion-current measurements is investigated. Molecular dynamics simulations and density functional theory calculations show that the metallacage spans the entire phospholipid bilayer as an unimolecular ion transport channel. This channel transports chloride ions across the cell membrane, which disturbs the ion balance of cancer cells and inhibits the growth of cancer cells at low concentrations.

Research Progress on the Transport and Prediction of Chloride Ions in Concrete Structures

Reinforced concrete structures are widely used in practical engineering, and the durability issues of such structures under chloride environments have been a hot research topic. Chloride ions can cause corrosion of internal steel bars in structures under the action of chloride salt, leading to structural cracking, decreased bearing capacity, and ultimately affecting the structural safety during service life. Therefore, comprehensive and systematic research on chloride ion transport and prediction in concrete structures is crucial. This paper reviews the recent research progress on chloride ion transport in concrete structures both domestically and internationally, introduces the latest research results on chloride ion transport mechanisms, transport laws, prediction methods, and points out the limitations and future research directions in existing research on chloride ion transport and prediction in concrete structures.

Circadian Rhythm Regulation by Pacemaker Neuron Chloride Oscillation in Flies.

Circadian rhythms in physiology and behavior sync organisms to external environmental cycles. Here, circadian oscillation in intracellular chloride in central pacemaker neurons of the fly, Drosophila melanogaster, is reviewed. Intracellular chloride links SLC12 cation-coupled chloride transporter function with kinase signaling and the regulation of inwardly rectifying potassium channels.

In vitro modulator responsiveness of 655 CFTR variants found in people with cystic fibrosis

BackgroundIn 2017, the US Food and Drug Administration initiated expansion of drug labels for the treatment of cystic fibrosis (CF) to include CF transmembrane conductance regulator (CFTR) gene variants based on in vitro functional studies. This study aims to identify CFTR variants that result in increased chloride (Cl−) transport function by the CFTR protein after treatment with the CFTR modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). These data may benefit people with CF (pwCF) who are not currently eligible for modulator therapies. MethodsPlasmid DNA encoding 655 CFTR variants and wild-type (WT) CFTR were transfected into Fisher Rat Thyroid cells that do not natively express CFTR. After 24 h of incubation with control or TEZ and ELX, and acute addition of IVA, CFTR function was assessed using the transepithelial current clamp conductance assay. Each variant's forskolin/cAMP-induced baseline Cl− transport activity, responsiveness to IVA alone, and responsiveness to the TEZ/ELX/IVA combination were measured in three different laboratories. Western blots were conducted to evaluate CFTR protein maturation and complement the functional data. Results and conclusions253 variants not currently approved for CFTR modulator therapy showed low baseline activity (<10 % of normal CFTR Cl− transport activity). For 152 of these variants, treatment with ELX/TEZ/IVA improved the Cl− transport activity by ≥10 % of normal CFTR function, which is suggestive of clinical benefit. ELX/TEZ/IVA increased CFTR function by ≥10 percentage points for an additional 140 unapproved variants with ≥10 % but <50 % of normal CFTR function at baseline. These findings significantly expand the number of rare CFTR variants for which ELX/TEZ/IVA treatment should result in clinical benefit.

Post-Consumer Carpet Fibers in Concrete: Fiber Behavior in Alkaline Environments and Concrete Durability.

The widespread use of carpets in residential and commercial buildings and their relatively short life span result in large volumes of carpet being landfilled. A potential solution to this problem is the use of post-consumer carpet fibers in concrete. To this end, this paper systematically identifies the common fiber types in a typical post-consumer carpet fiber bale and evaluates their durability under exposure to varying levels of alkalinity. The tensile strengths and toughness of the fibers belonging to the nylon and polyethylene terephthalate (PET) families (the dominant fibers in most post-consumer carpets) are reduced by up to 50% following exposure to extreme alkalinity, the reasons for which are determined using spectroscopic and microscopic evaluations. The chloride ion transport resistance of concretes (~40 MPa strength) containing 2.5% carpet fibers by volume (~25 kg of fibers per cubic meter of concrete) is comparable to that of the control mixture, while mortar mixtures containing the same volume fraction of carpet fibers demonstrate negligible enhancement in expansion and loss of strength when exposed to 1 N NaOH. This study shows that moderate-strength concretes (~40 MPa) for conventional building and infrastructure applications can be proportioned using the chosen volume of carpet fibers without an appreciable loss of performance. Consideration of low volume fractions of carpet fibers in low-to-moderate-strength concretes thus provides a sustainable avenue for the use of these otherwise landfilled materials in construction applications.

Investigation of the chloride ion transport mechanism in unsaturated concrete considering the nonlinear seepage effect

In this paper, the mechanism of chloride ion transport in unsaturated concrete considering the nonlinear seepage effect is investigated by indoor experiments and analytical modelling. The concrete sheet imbibition test is used to reveal the nonlinear characters of seepage including water convection and moisture capillary within the unsaturated concrete in case of various water-binder ratios. For modelling purpose, an exponential function is introduced to mathematically depict the nonlinear relation between the specific discharge and hydraulic gradient during both water convection and moisture capillary processes. Based on such nonlinear seepage models, new mathematical models are proposed for the problem of chloride invasion within the reinforced concrete structure. The solution for the mathematical model of chloride transport is resolved by Laplace transform and finite difference method, of which acceptability is verified by the comparison with the results from chloride ion invasion test. The result indicates that, compared with linear seepage law, the use of the proposed nonlinear seepage solution is preferred to depict the saturation-relative humidity curves from concrete sheet imbibition test. The consideration of nonlinear seepage can result in a slower chloride transport rate, which further makes a later flow start-up time and a smaller free chloride iron concentration within the concrete. Such effect can be enhanced with the increase of nonlinear flow degree. The paper provides an effective solution to evaluate the chloride invasion within the unsaturated concrete.

Effect of surface activity of recycled fine aggregates from clay bricks on the hydration, microstructure and chloride transport of concrete

Use of recycled fine aggregates from clay bricks (RFCB) in the preparation of eco-friendly concrete was proposed to tackle the river sand (RS) shortage and satisfy the construction demand. This study explored the surface activity of RFCB influenced by additional water and particle size distribution (PSD) on the hydration, microstructure and chloride transport of concrete. Compared to the RS, more silica and alumina released from RFCB depending on its PSD under alkaline environment was noted, which verified its appreciable surface activity. Overall, the presence of RFCB could hinder early hydration process because of the higher additional water, while the surface activity and nucleation effect supplied from finer RFCB were beneficial for the improvement of the hydration kinetics. Furthermore, inclusion of RFCB increased the total pore volume and porosity but performed better in refining the pore size distribution, thus decreased the average pore diameter. The surface activity of RFCB decreased CH content while increased chemical bond water and additional hydrates, thereby leading to enhancement of the compactness of interface, cement matrix and surface rim. More importantly, RFCB helped to decrease the chloride migration coefficient and electric flux. Though the surface activity of RFCB was beneficial in the strength development, it could not offset a deteriorated influence of porous RFCB with a higher replacement.

Experimental and Numerical Study on Chloride Transport in Unsaturated Concrete: Highlighting Temperature, Humidity, and Mineral Admixtures.

Chloride transport within concrete is critical for the durability of reinforced concrete structures; however, its diffusion under the coupling action of temperature and humidity has not been fully comprehended. Therefore, in this work, the coupling effects of temperature, relative humidity, and mineral admixtures on chloride transport in concrete were investigated through experimental and numerical simulation work. The results show that the chloride diffusion coefficient decreases with the decreased temperature and growth of relative humidity; however, the chloride concentration on the concrete surface is increased with the growth of temperature and relative humidity. Moreover, compounding about 15% fly ash (FA) and 30% granulated ground blast furnace slag (GGBS) to replace the cement is the most beneficial for improving the antichloride capacity of concrete, considering also the strength. In addition, the numerical simulation considering the coupled effect of temperature and relative humidity of chloride transport in concrete has good agreement with that of experimental results.

The Cl- transporter ClC-7 is essential for phagocytic clearance by microglia.

Microglia, professional phagocytic cells of the brain, rely upon the appropriate activation of lysosomes to execute their immune and clearance functions. Lysosomal activity is, in turn, modulated by a complex network of over 200 membrane and accessory proteins that relay extracellular cues to these key degradation centers. The ClC-7 chloride (Cl-)-proton (H+) antiporter (also known as CLCN7) is localized to the endolysosomal compartments and mutations in CLCN7 lead to osteopetrosis and neurodegeneration. Although the functions of ClC-7 have been extensively investigated in osteoclasts and neurons, its role in microglia in vivo remains largely unexamined. Here, we show that microglia and embryonic macrophages in zebrafish clcn7 mutants cannot effectively process extracellular debris in the form of apoptotic cells and β-amyloid. Despite these functional defects, microglia develop normally in clcn7 mutants and display normal expression of endosomal and lysosomal markers. We also find that mutants for ostm1, which encodes the β-subunit of ClC-7, have a phenotype that is strikingly similar to that of clcn7 mutants. Together, our observations uncover a previously unappreciated role of ClC-7 in microglia and contribute to the understanding of the neurodegenerative phenotypes that accompany mutations in this channel.

The Lucigenin Assay: Measuring Anion Transport in Lipid Vesicles

AbstractInvited for this month′s cover are the collaborating groups of the Université libre de Bruxelles and Masaryk University. The cover picture shows liposomes with a fluorescent probe encapsulated to study the transmembrane transport of chloride by synthetic anion transporters via quenching of the fluorescence. More information can be found in the Concept article by Hennie Valkenier and co‐workers.

Mimicking the Shape and Function of the ClC Chloride Channel Selective Pore by Combining a Molecular Hourglass Shape with Anion-π Interactions.

ClC is the main family of natural chloride channel proteins that transport Cl- across the cell membrane with high selectivity. The chloride transport and selectivity are determined by the hourglass-shaped pore and the filter located in the central and narrow region of the pore. Artificial unimolecular channel that mimics both the shape and function of the ClC selective pore is attractive, because it could provide simple molecular model to probe the intriguing mechanism and structure-function relevance of ClC. Here we elaborated upon the concept of molecular hourglass plus anion-π interactions for this purpose. The concept was validated by experimental results of molecular hourglasses using shape-persistent 1,3-alternate tetraoxacalix[2]arene[2]triazine as the central macrocyclic skeleton to control the conductance and selectivity, and anion-π interactions as the driving force to facilitate the chloride dehydration and movement along the channel.

Developmental loss of NMDA receptors results in supernumerary forebrain neurons through delayed maturation of transit-amplifying neuroblasts

Developmental neurogenesis is a tightly regulated spatiotemporal process with its dysregulation implicated in neurodevelopmental disorders. NMDA receptors are glutamate-gated ion channels that are widely expressed in the early nervous system, yet their contribution to neurogenesis is poorly understood. Notably, a variety of mutations in genes encoding NMDA receptor subunits are associated with neurodevelopmental disorders. To rigorously define the role of NMDA receptors in developmental neurogenesis, we used a mutant zebrafish line (grin1−/−) that lacks all NMDA receptors yet survives to 10 days post-fertilization, offering the opportunity to study post-embryonic neurodevelopment in the absence of NMDA receptors. Focusing on the forebrain, we find that these fish have a progressive supernumerary neuron phenotype confined to the telencephalon at the end of embryonic neurogenesis, but which extends to all forebrain regions during postembryonic neurogenesis. This enhanced neuron population does not arise directly from increased numbers or mitotic activity of radial glia cells, the principal neural stem cells. Rather, it stems from a lack of timely maturation of transit-amplifying neuroblasts into post-mitotic neurons, as indicated by a decrease in expression of the ontogenetically-expressed chloride transporter, KCC2. Pharmacological blockade with MK-801 recapitulates the grin1−/− supernumerary neuron phenotype, indicating a requirement for ionotropic signaling. Thus, NMDA receptors are required for suppression of indirect, transit amplifying cell-driven neurogenesis by promoting maturational termination of mitosis. Loss of suppression results in neuronal overpopulation that can fundamentally change brain circuitry and may be a key factor in pathogenesis of neurodevelopmental disorders caused by NMDA receptor dysfunction.

Cystic Fibrosis Lung Disease: A Narrative Literature Review

Cystic fibrosis (CF) is caused by mutations in autosomal recessive genes that code for proteins cystic fibrosis transmembrane conductance regulator (CFTR) which is located on chromosome seven. The CFTR protein under normal conditions acts as a chloride channel and helps the movement of sufficient electrolytes and water across the membrane. Mutations in CFTR cause abnormalities in chloride ion transport through epithelial cells and impaired sodium and water transport resulting in viscous secretions with low water content. This thick and sticky secretion will inhibit the normal function of various organs, although pulmonary complications are the most common cause of death. Cystic fibrosis has wide genotypic and phenotypic variations. There are six categories of mutations based on their effect on the CFTR protein, where these categories are not only used to predict the phenotype but also to determine better therapeutic strategies based on the identified mutations.

Mesoscopic statistics-based probability characteristics of chloride transport and reliability-based corrosion initiation life of bridge tower

Chloride-induced corrosion involves multiple factors and uncertainties. This study focuses on the probabilistic and multifactorial prediction model for the reliability and service life of reinforced concrete structures in marine environments. We present a new probabilistic framework to quantify the uncertainty of chloride transport by mesoscopic statistics and Spearman correlation analysis and develop a modified chloride transport model, incorporating multi-factors such as time dependence, admixture usage, temperature, relative humidity, stress level, freeze-thaw cycles, chloride binding capacity, aggregate volume fraction, aggregate particle size, and concrete deterioration. Taking the Shenzhen-Zhongshan Bridge as an example, by considering the chloride diffusion coefficient, concrete cover thickness, convection zone thickness, critical chloride concentration, and surface chloride concentration as random variables, the first-order reliability method (FORM) was employed to determine the time-variant reliability index and service life of the example bridge in different environmental conditions, encompassing atmospheric, splashing, tidal, and submerged zones. The sensitivity of the time-variant reliability to these random variables and the impact of the non-random variables on the reliability index were investigated quantitatively and comparatively. The findings reveal significant temporal and spatial variability in chloride diffusion coefficients due to the random arrangement of aggregates within concrete. The study demonstrates that concrete cover thickness and chloride diffusion coefficient are the most influential variables on structural reliability and emphasizes the substantial impact of admixtures, concrete deterioration, and environmental factors on the time-variant reliability. This research offers a significant reference in the reliability design, safety assessment, and maintenance of concrete structures in chloride-rich environments.

Interaction and Transport of Benzalkonium Chlorides by the Organic Cation and Multidrug and Toxin Extrusion Transporters.

Humans are chronically exposed to benzalkonium chlorides (BACs) from environmental sources. The U.S. Food and Drug Administration (FDA) has recently called for additional BAC safety data, as these compounds are cytotoxic and have great potential for biochemical interactions. Biodistribution studies revealed that BACs extensively distribute to many tissues and accumulate at high levels, especially in the kidneys, but the underlying mechanisms are unclear. In this study, we characterized the interactions of BACs of varying alkyl chain length (C8 to C14) with the human organic cation transporters (hOCT1-3) and multidrug and toxin extrusion proteins (hMATE1/2K) with the goal to identify transporters that could be involved in BAC disposition. Using transporter-expressing cell lines, we showed that all BACs are inhibitors of hOCT1-3 and hMATE1/2K (IC50 ranging 0.83-25.8 μM). Further, the short-chain BACs (C8 and C10) were identified as substrates of these transporters. Interestingly, although BAC C8 displayed typical Michaelis-Menten kinetics, C10 demonstrated a more complex substrate-inhibition profile. Transwell studies with transfected Madin-Darby canine kidney cells revealed that intracellular accumulation of basally applied BAC C8 and C10 was substantially higher (8.2- and 3.7-fold, respectively) in hOCT2/hMATE1 double-transfected cells in comparison with vector-transfected cells, supporting a role of these transporters in mediating renal accumulation of these compounds in vivo. Together, our results suggest that BACs interact with hOCT1-3 and hMATE1/2K as both inhibitors and substrates and that these transporters may play important roles in tissue-specific accumulation and potential toxicity of short-chain BACs. Our findings have important implications for understanding human exposure and susceptibility to BACs due to environmental exposure. SIGNIFICANCE STATEMENT: Humans are systemically exposed to benzalkonium chlorides (BACs). These compounds broadly distribute through tissues, and their safety has been questioned by the FDA. Our results demonstrate that hOCT2 and hMATE1 contribute to the renal accumulation of BAC C8 and C10 and that hOCT1 and hOCT3 may be involved in the tissue distribution of these compounds. These findings can improve our understanding of BAC disposition and toxicology in humans, as their accumulation could lead to biochemical interactions and deleterious effects.