Chloride Transport Research Articles

Sinus Symptoms in Cystic Fibrosis Patients and the Role of Interdisciplinary Care

Chronic rhinosinusitis (CRS) is known to occur in most cystic fibrosis (CF) patients. This phenomenon occurs because the genetic mutations in CF cause impaired chloride ion transport, which affects water transport and thus leads to thick mucus that cannot be cleared easily in both the lower and upper airways. While improvements continue to be made in treatment modalities for CF patients in terms of modulator therapies, the effect on sinus disease symptoms and the role of the otolaryngologist (ENT) continues to evolve. This study investigates the sinus symptoms of CF patients with comparison to ENT involvement in their care, the histories of polyps and sinus surgeries of these CF patients, and how their initiation to modulator treatment has affected ENT involvement in their care. A retrospective health records review was conducted including patients from Augusta University Adult Cystic Fibrosis Center with stratification based on demographics, mutations, modulators, ENT clinic visits, history of polyps or nasal surgery, and reported symptoms of headaches, olfactory dysfunction, and sleep problems. 98 patients of the Augusta University Adult Cystic Fibrosis Center met the inclusion criteria of this study. Most of the patients with reported ENT visits in the past 10 years were white and between the ages of 20-29. The most common modulator therapy of the CF patients was elexacaftor-tezacaftor-ivacaftor at 72.22%. More than half of the patients had a history of sinonasal surgery, and almost half had a history of polyps. In comparing ENT visits to the initiation of modulator therapy, 24% of the patients with reported ENT visits saw an ENT after starting modulator therapy. CRS can contribute to morbidity in CF patients with most patients requiring surgical intervention in their lifetime. Additionally, persistent sinonasal symptoms can reduce the quality of life in CF patients. Despite treatment with modulator therapies, otolaryngologists continue to have a role in interdisciplinary CF management.CF- Cystic Fibrosis; CFTR- Cystic Fibrosis Transmembrane Regulator; CRS- Chronic Rhinosinusitis; EMR- Electronic Medical Record; ENT- Otolaryngologist

Improved chloride transport resistance of cement mortar using quartz sands modified with MgAl-LDH

The chloride transport into concrete is responsible for the durability deterioration of concrete under chloride-laden conditions. This paper aims to restrict the chloride transport into mortar by the partial replacement of fine aggregates with the quartz sands modified by MgAl-LDH, which were prepared by the co-precipitation method. The microstructures of modified sands and mortars were characterized. Besides, the chloride transport properties in mortar were evaluated by the rapid chloride migration test and long-term chloride diffusion test. The results indicate that quartz sands with in-situ-growth MgAl-LDH have improved specific surface area and chloride binding capacity. With the replacement ratio of modified sands increasing, the resistance of mortar against chloride penetration is significantly improved. The reason for the improved chloride transport resistance may be due in part to the improvement of the microstructure of ITZ, but more importantly, to the chloride ions immobilization of the modified quartz sand.

Chloride profiles – What do they tell us and how should they be used?

Chloride profiles are used to select concrete compositions for new reinforced concrete structures, evaluate the condition of existing structures, and to predict their remaining service life, all with regard to chloride-induced reinforcement corrosion. They are invaluable tools for improving the sustainability of our infrastructure. We examine what chloride profiles tell us and how they should be used. Through a series of case studies, we establish a list of crucial research questions that provide a direction for future research in this field: What is the contribution of chloride binding to chloride transport? What is the path for chloride transport in concrete? How are our findings on chloride profiles relevant for reinforcement corrosion? We then discuss the implications of the answers to these questions for engineering and mechanistic modelling practices.

Experimental study on chloride ion diffusion behavior and microstructure in concrete under alternating ambient humidity conditions

The migration of chloride in concrete in atmospheric zones is mainly influenced by climatic conditions, e.g., various dry-wet cycles in marine tidal zones, and ambient humidity is one of the most important influences. Ambient humidity also determines the moisture content in concrete, which is necessary for the diffusion or transport of chloride in concrete and can enhance the migration of chloride in micropores, thus affecting the distribution of chloride in concrete. In this study, the effects of chloride diffusion and its mechanism, and the evolution of moisture in concrete under alternating drying-wetting cycles, were investigated using an environmental moisture simulation chamber. Chloride diffusion tests were also performed to evaluate the effects of different dry-wet ratios and numbers of drying-wetting cycles on the chloride diffusion depth, chloride content and saturation in concrete. The microstructure of concrete was studied and analyzed using XRD, SEM and MIP technology. The findings showed that the saturation of concrete decreased rapidly with increasing number of wet-dry cycles and finally stabilized. Under different alternating moisture conditions, the saturation of concrete was greater, especially when the wetting time was longer. Additionally, in areas near the surface of concrete (depths of 2 mm-6 mm), the chloride content was proportional to the number of wet-dry cycles. In the interior of concrete (depth > 6 mm), when the number of drying-wetting cycles was larger, the chloride concentration was smaller. However, as the number of wet-dry cycles increased, this led to the decalcification of C-S-H gels, which resulted in the reduction in the number of C-S-H reticular gels with good crystallinity. A pore analysis showed that the cumulative pore size and the maximum probability pore size of concrete gradually increased with increasing number of wet-dry cycles, the deterioration of pore structure was more obvious, and the compactness of concrete gradually decreased, which accelerated the migration of chloride in the matrix. Overall, this study can provide reliable and valuable test data for the development and design of high-performance concrete for applications in atmospheric marine tidal zones.

Enhancement of a multi-species reactive transport model for cement-based materials under cyclic wetting and drying conditions

To understand the underlying phenomena that drive concrete deterioration under cyclic environmental conditions in the marine environment, a reactive transport model (RTM) for unsaturated cement-based materials has been established in this study, including multi-ionic and moisture transport coupled with a chemical equilibrium computation. The two-phase moisture transport model, which considers pore structure changes, is introduced with capillary pressure as the primary variable parameter. The modified Poisson-Nernst-Planck (PNP) equations were illustrated for multi-ionic transport through pore solution under unsaturated conditions. A modelling approach for moisture conductivity based on the pore structure and moisture storage was presented to account for pore structure changes on the mass transports. The consideration of boundary conditions and moisture flux through the exposed surface is demonstrated for wetting and drying conditions, separately. Numerical results for mortar samples subjected to NaCl solutions under various cyclic wetting and drying conditions were in good agreement with experimentally measured moisture gain and total chloride content. Under more prolonged wetting conditions, the deeper influence depth and a wider range of moisture fluctuation lead to an increase in concrete deterioration. For all cyclic wetting conditions, the precipitation of Friedel's salt is predicted, which subsequently limits the transport of chloride ions to deeper depths from the exposed surface. A peak in the chloride profile is observed near the exposed surface. Meanwhile, the peak region continuously expands and moves deeper into the specimens with increasing wetting time duration and exposure times, consistent with Friedel's salt precipitation. In contrast, the chloride content near the exposure surface shows a significant decrease due to the decomposition of the C–S–H phase caused by ion leaching and carbonation of the exposed surface.

Urea transport in human red blood cells: Donor variation compared to chloride, glucose, and water transport.

We determined the permeability (P, cm/s) of unmodified human red blood cells (HRBC) to urea (Pu), chloride (PCl), glucose (Pglu), and water diffusion (Pd) under conditions of self-exchange (SE) with the continuous flow tube method at pH 7.2, 25°C. Among 24 donors, Pu at 1 mM varied >100%. Two of the donors were also tested in 1983. Their Pu had decreased by 77 and 90%. High age in males and Kidd genotype Jk(a+,b+), but not blood types AB0, appear related to low Pu. For one of the two donors, PCl (150 mM, 38°C, pH 7.2), Pglu (1 mM, 38°C, pH 7.2), and Pd (55.5 M, 25°C, pH 7.2) were determined then and now and showed no significant changes with age. The results from six more donors show donor PCl, Pglu, and Pd in the range of ≈1%. PCl and Pglu are vital for the metabolism of cells and tissues, and we see but little donor variation, and so far, no phenotypes without glucose (GLUT1) and anion (AE1) transporters in HRBC. Phenotypes with no urea transporter (UT-B) or no water transporters (aquaporin, AQP1) are registered and are compatible with life. Our results are in line with the concept that the solutes do not share pathways in common. The great donor variation in Pu must be considered in comparative transport physiological studies.

Personalized CFTR Modulator Therapy for G85E and N1303K Homozygous Patients with Cystic Fibrosis.

CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has been approved for people with CF and at least one F508del allele in Europe. In the US, the ETI label has been expanded to 177 rare CFTR mutations responsive in Fischer rat thyroid cells, including G85E, but not N1303K. However, knowledge on the effect of ETI on G85E or N1303K CFTR function remains limited. In vitro effects of ETI were measured in primary human nasal epithelial cultures (pHNECs) of a G85E homozygous patient and an N1303K homozygous patient. Effects of ETI therapy in vivo in these patients were assessed using clinical outcomes, including multiple breath washout and lung MRI, and the CFTR biomarkers sweat chloride concentration (SCC), nasal potential difference (NPD) and intestinal current measurement (ICM), before and after initiation of ETI. ETI increased CFTR-mediated chloride transport in G85E/G85E and N1303K/N1303K pHNECs. In the G85E/G85E and the N1303K/N1303K patient, we observed an improvement in lung function, SCC, and CFTR function in the respiratory and rectal epithelium after initiation of ETI. The approach of combining preclinical in vitro testing with subsequent in vivo verification can facilitate access to CFTR modulator therapy and enhance precision medicine for patients carrying rare CFTR mutations.

Investigating the chloride ion resistance of cracked concrete through Reverse-seepage and Saturation based Action Anti-corrosion Tech (RS-AAT): Experimental and numerical analysis

This study investigates the chloride ions transport in cracked concrete with the impact of RS-AAT (Reverse-seepage and Saturation based Action Anti-corrosion Tech) in the environment of wet-dry cycling and soaking conditions. With the effect of reverse water pressure, the chloride ions accumulation surrounding the crack on the concrete surface and the chloride ions penetration within the concrete along the cracks are demonstrated by the indoor experiments. A two-dimensional convective diffusion model of chloride ions in cracked concrete is established to simulate the correlation between crack size and the change of reverse water pressure. Four types of cracks with widths of 0 mm, 0.2 mm, 0.4 mm and 1 mm, and a depth of 20 mm were selected. Three types of water pressures with values of 0.2 MPa, 0.3 MPa and 0.4 MPa were used for the technique. The experimental results show that the anti-convection effect induced by the reverse water pressure can inhibit the accumulation of chloride ions around the cracks and effectively limit the intrusion of chloride ions into the concrete protection layer. With the increase of reverse water pressure, the inhibition effect of seepage flow on chloride ions is more obvious. The experimental findings provide valuable references for investigating marine concrete durability and resistance to chloride ion erosion.

Mechanisms of chloride transport in low carbon marine concrete: An alkali-activated slag system with high limestone powder

Mechanisms of chloride transport in low carbon marine concrete: An alkali-activated slag system with high limestone powder

Potential Hydrologic Pathways of Deicing Salt Chloride Transport Evaluated with SWMM

Potential Hydrologic Pathways of Deicing Salt Chloride Transport Evaluated with SWMM

Synthesis and Evaluation of Bithiazole Derivatives As Potential α-Sarcoglycan Correctors.

4'-Methyl-4,5'-bithiazoles were previously identified as cystic fibrosis transmembrane regulator (CFTR) correctors, thus being able to correct folding defective mutants of the channel regulating chloride transport through the membrane. Additionally, bithiazole derivative C17 was reported to recover α-sarcoglycan in vitro and in vivo. We report here the synthesis of two new derivatives of C17, in which the two sides of the bithiazole scaffold were modified. The synthesized compounds and the corresponding precursors were tested in myogenic cells to evaluate the expression of α-sarcoglycan. The results highlighted that both substitutions of the bithiazole scaffold are important to achieve the maximum recovery of the α-sarcoglycan mutant. Nonetheless, partial preservation of the activity was observed. Accordingly, this paves the way to further derivatizations/optimization and target fishing studies, which were preliminarily performed in this study as a proof of concept, allowing the investigation of the molecular mechanisms leading to the α-sarcoglycan correction.

Cystic fibrosis

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by variants in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR dysfunction results in abnormal chloride and bicarbonate transport in epithelial cells, leading to a multiorgan disease dominated by respiratory and digestive manifestations. The respiratory disease, which is characterized by airway mucus plugging, chronic bacterial infection and progressive development of bronchiectasis, may lead to chronic respiratory failure, which is the main cause of premature death in people with CF. Over the past 50 years, major progress has been obtained by implementing multidisciplinary care, including nutritional support, airway clearance techniques and antibiotics in specialized CF centers. The past 10 years have further seen the progressive development of oral medications, called CFTR modulators, that partially restore ion transport and lead to a major improvement in clinical manifestations and lung function, presumably resulting in longer survival. Although an increasing proportion of people with CF are being treated with CFTR modulators, challenges remain regarding access to CFTR modulators due to their high cost, and their lack of marketing approval and/or effectiveness in people with rare CFTR variants. The anticipated increase in the number of adults with CF and their aging also challenge the current organization of CF care. The purpose of this review article is to describe current status and future perspective of CF disease and care.

Reusing thermoactivated construction waste spoil as sustainable binder for durable concrete: Microstructure and chloride transport

Construction and demolition waste is predominantly comprised of construction spoil. However, the proper recycling of this construction spoil in a manner that maximizes its value has historically received insufficient attention. Therefore, the objective of this study investigated the micro-structure and chloride transport of cement concrete including thermoactivated construction spoil powder (CSP) as a substitute for cement. The results highlights that the un-treated CSP consisted of massive inert components, and active metakaolin and amorphous components were generated in thermoactivated CSP after 800–1200 ℃ activation treatment. Mixing un-treated CSP negatively impacted the micro-structure and strength development of concrete, but the thermoactivated CSP blended paste had improved micro-structure and better strength than the un-treated CSP blended paste. Incorporating un-treated CSP raised the chloride transport in concrete. At the constant replacement ratio of CSP, the thermoactivated CSP blended concrete had lower chloride transport than the un-treated CSP blended concrete, and decreasing the particle size of thermoactivated CSP could further decline the chloride transport in thermoactivated CSP blended concrete. The concrete with 1200 ℃-activated CSP even had lower chloride transport than the reference concrete. The mix of un-treated CSP up to 30% reduced the chloride binding capacity of concrete, but the thermoactivated CSP blended concrete had superior chloride binding capacity to the un-treated CSP blended concrete. Particularly, the concrete with 20% thermoactivated CSP and 10% active metakaolin/silica fume had similar strength and lower chloride transport than reference concrete. By optimizing the thermoactivation temperature, replacement ratio, and particle size of CSP, it was possible to prepare a durable concrete with low chloride transport.

Transmembrane Transport of Inorganic Phosphate by a Strapped Calix[4]pyrrole.

Synthetic anion receptors are increasingly being explored for the transport of anions across lipid membranes because of their potential therapeutic applications. A considerable amount of research focuses on the transport of chloride, whereas the transmembrane transport of inorganic phosphate has not been reported to date, despite the biological relevance of this anion. Here we present a calix[4]pyrrole with a bisurea strap that functions as a receptor and transporter for H2PO4-, relying on the formation of eight hydrogen bonds and efficient encapsulation of the anion. Using a phosphate-sensitive lanthanide probe and 31P NMR spectroscopy, we demonstrate that this receptor can transport phosphate into vesicles by H2PO4-/Cl- antiport, H2PO4- uniport, and Cs+/H2PO4- symport mechanisms. This first example of inorganic phosphate transport by a neutral receptor opens perspectives for the future development of transporters for various biological phosphates.

Stray current induced chloride ion transport and corrosion characteristics of cracked ultra-high performance concrete

Ultra-high-performance concrete (UHPC) is a strong, durable, and corrosion-resistant material that is poised to revolutionize construction in complex environments, such as the deep sea and underground. However, the formation of cracks of UHPC during service and the occurrence of stray currents in underground stations and tunnels greatly accelerate the transport of chloride ions, posing a threat to the safety of underground construction. Here, we used the rapid chloride migration (RCM) method to study the effect of stray current in cracked UHPC. Essentially, electric field accelerates chloride ion transport in cracks by increasing ion transport in the uncracked zone. The wider the crack, the more severe the corrosion of steel fibers, which affects the pore structure of UHPC and leads to an increase in the diffusion coefficient in the uncracked area. In addition, area normalization was employed to precisely monitor the chloride ion concentration in the cracks, which was validated by numerical simulations. Finally, microscopy and atomic force microscopy (AFM) showed that larger crack widths led to deeper corrosion and more severe steel fiber corrosion in UHPC. These results have important implications for the durability design of UHPC structures in stray current environments.

Relationship between chloride ion permeation resistance of ultra-high performance concrete and lightweight aggregate ratio

This paper investigates the effects of different substitution rates of lightweight aggregate (LWA) on the workability, mechanical properties, and chloride ion permeability of ultra-high performance concrete (UHPC). A two-dimensional model based on the random distribution of irregular LWA particles was established to simulate chloride diffusion. Based on experimental and simulation results, the influencing mechanism of LWA substitution rate on the chloride ion penetration resistance of UHPC was further explored. The results indicate that during the LWA mixing process, its porous structure causes premature release of water involved in internal curing, leading to degradation of the pore structure and interfacial transition zone. Therefore, with the increase of LWA substitution rate, not only does the working and mechanical properties of UHPC decrease, but also the chloride ion transport channels increase, leading to an accelerated migration rate of chloride ions in UHPC.

Experimental and modelling investigation on chloride transport and flexural behaviour of RC beams subjected to simultaneous deteriorating factors of carbonation, FT cycles and multi-type sustained stress

Reinforced concrete (RC) structures are often exposed to coinstantaneous deterioration effects such as carbonation, chloride corrosion, freeze–thaw cycles and external loads which causing deterioration of concrete and reinforcement. This paper discussed the effects of carbonation, freeze–thaw cycles and sustained loads on chloride ion transport and proposed a chloride ion transport model taking porosity as the main coupling variate. The attenuation law of the corroded beams under coupling corrosion factors was studied. Through chloride immersion tests, it was found that applying freezing and thawing cycles and sustained tensile stress can enhance chloride transport capacity by coarsening the pores; Carbonation and low compressive stress can repress the chloride ion transport by densifying concrete, but the compressive stress beyond about 0.7 times the compressive strength and tensile stress would enhance the penetrating capacity due to the damage of the internal microstructure of concrete. Then, a comprehensive and unified theoretical model of chloride ion transport considering the coupling of carbonation, freeze–thaw cycle, sustained loading and other factors was proposed and verified by taking porosity as the main coupling variable quantity. This model could essentially explain the effects of various factors on chloride ion transport and has good consistency with the test results. Finally, the flexural bearing capacity of the corroded beams was tested, and the failure characteristics, crack characteristics, ultimate bearing capacity, load–displacement relationship and strain distribution of the corroded beams under different corrosion conditions were researched. The results show that the flexural capacity of the corroded beams suffered the coupling effects of multiple corrosion factors degrades, and the bearing capacity decreases with the increase of the corrosion degree of carbonation-freezing thawing cycles; The continuous tensile stress applied to the test beams in the corrosion process intensifying the degradation of bending bearing capacity and ductility, the continuous compressive stress increases the flexural capacity and improves the ductility slightly, but excessive compressive stress significantly degrades the flexural capacity; When chloride ions are used as the third kind of corrosive substance for coupling corrosion, the tensioned or without-load corroded beams have obvious degradation in bending bearing capacity, while the corrosion beams bearing continuous compressive stress have no obvious degradation in bending bearing capacity.

Using recycled aggregate and powder from high-strength mortar waste for durable cement-based materials: Microstructure and chloride transport

The large-scale application of high-strength mortar in engineering will inevitably generate a significant amount of high-strength mortar waste in future, but there has been relatively limited research to date on the reuse of high-strength mortar waste as recycled building materials. Therefore, this paper studied the microstructure and chloride transport in cement-based materials using recycled fine aggregate (HCRA) and recycled powder (HCRP) derived from high-strength mortar waste or from high-strength mortar waste separated from high-strength concrete waste recycling. HCRA had much better physical and mechanical properties than ordinary recycled aggregate. HCRP contained some active components, and mixing appropriate HCRP refined paste pore structure; besides, reducing HCRP particle size could further refine the pore diameter of HCRP doped mortar. The strength of mortar first raised and then declined with the increment of HCRA replacement, but the strength decreased as HCRP was incorporated. Incorporating HCRA slightly reduced the chloride migration in mortar, and the mortar with HCRA had better chloride resistance than the mortar with recycled fine aggregate crushed from ordinary mortar waste. Mixing appropriate HCRP could reduce the chloride diffusion coefficient and chloride concentration. Reducing HCRP particle size further declined the chloride transport in HCRP blended mortar, and the mortar with HCRP had superior chloride resistance to the mortar with ordinary recycled powder. Mixing HCRA and HCRP both raise the chloride binding capacity. Particularly, fully recycled mortar with 100% HCRA and 30% HCRP exhibited even better chloride resistance than reference mortar. Incorporating appropriate HCRA and HCRP could prepare durable cement-based materials with good chloride resistance.

Physics-informed deep neural network for modeling the chloride diffusion in concrete

Chloride diffusion in concrete is a complex chemo-physical process and it is of pivotal importance to forecast the initiation time of corrosion. But limited equations are accessible to simulate the chloride diffusion considering the nonlinear chloride binding capacity of concrete. This study proposes a physics-informed deep neural network to simulate the chloride diffusion mechanism and forecast the distribution of chloride concentrations in concrete. Physical laws are formulated as a loss term to guide the training process and to mitigate the data required for model training. The physical constraint loss (based on the governing equation and boundary conditions) and the training loss (based on the neural network) are then fused to produce the loss function. Different experimental cases are first employed to validate the proposed model and then the model is compared to numerical applications and purely data-driven approaches. Results revealed that the proposed model could effectively simulate the chloride transport behavior and forecast the diffusion coefficient of concrete with high precision over other states of art methods. The application of this method to the temporal and spatial domains of the chloride concentration within the concrete samples showed its potential as a powerful tool for investigating concrete properties.

The chloride antiporter CLCN7 is a modifier of lysosome dysfunction in FIG4 and VAC14 mutants.

The phosphatase FIG4 and the scaffold protein VAC14 function in the biosynthesis of PI(3,5)P2, a signaling lipid that inhibits the lysosomal chloride transporter ClC-7. Loss-of-function mutations of FIG4 and VAC14 reduce PI(3,5)P2 and result in lysosomal disorders characterized by accumulation of enlarged lysosomes and neurodegeneration. Similarly, a gain of function mutation of CLCN7 encoding ClC-7 also results in enlarged lysosomes. We therefore tested the ability of reduced CLCN7 expression to compensate for loss of FIG4 or VAC14. Knock-out of CLCN7 corrected lysosomal swelling and partially corrected lysosomal hyperacidification in FIG4 null cell cultures. Knockout of the related transporter CLCN6 (ClC-6) in FIG4 null cells did not affect the lysosome phenotype. In the Fig4 null mouse, reduction of ClC-7 by expression of the dominant negative CLCN7 variant p.Gly215Arg improved growth and neurological function and increased lifespan by 20%. These observations demonstrate a role for the CLCN7 chloride transporter in pathogenesis of FIG4 and VAC14 disorders. Reduction of CLCN7 provides a new target for treatment of FIG4 and VAC14 deficiencies that lack specific therapies, such as Charcot-Marie-Tooth Type 4J and Yunis-Varón syndrome.