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Chloride-induced corrosion is the leading cause of structural performance deterioration and life decay in marine environments. This paper delves into the mesoscopic characteristics and spatiotemporal variability of chloride transport in concrete. We conducted extensive mesoscopic simulations to reveal the effects of ITZ and aggregate volume fraction, morphology, size, and particle quantity on chloride transport. We identified the probability characteristics of chloride concentration and diffusion coefficient based on statistical analysis of the mesoscopic simulation results. We proposed a novel probabilistic framework and predictive model for chloride diffusion coefficients incorporating aggregate parameters like volume fraction and particle size. The findings of this study demonstrate that the chloride transport shows noteworthy spatiotemporal variability; the aggregate size effect, aggregate particle quantity effect, and the local effect of large aggregates are all significant characteristics of the chloride transport in addition to the pre-discovered dilution effect, tortuosity effect, and ITZ effect. The chloride diffusion coefficient approximately follows a log-normal distribution, whereas the chloride concentration roughly follows a normal or log-normal distribution. The findings in this work are instrumental in predicting the probabilistic chloride transport and service life of reinforced concrete structures. • Revealing the spatiotemporal variability of chloride transport in concrete. • Identifying the statistical characteristic of chloride concentration distribution. • Proposing a new probabilistic framework of chloride diffusion coefficient. • Discovering some new mesoscopic characteristics of chloride transport. [ABSTRACT FROM AUTHOR]

In recent years, microbial-induced carbonate precipitation (MICP) is becoming a popular method of soil stabilisation and concrete crack healing. In MICP, calcium is a necessary reactant, and pH value is a crucial factor for living bacteria. Both parameters (i.e., calcium and pH) are adjustable for geopolymer concrete mix design. Given the attractive potential for future applications of geopolymer concrete, understanding the impact of calcium content and pH value of MICP crack healing in geopolymer concrete mix design is of great importance. In this study, it was found that high calcium content in geopolymer concrete mix design is helpful to improve the healing effect. When CaO% in mix design increases from 7.5 % to 18.3 %, the healing degree increases. When Na 2 O% increases from 4.4 % to 11.6 %, the pH value of geopolymer concrete is improved by around 1, and it was also found that the impact of pH value depends on the way healing is implemented. In the case where bacteria were applied from outside of the healing surface cracks, the effect of pH value was almost negligible. However, when bacteria were used for internal healing, the lower pH value of the geopolymer mix design was beneficial for bacteria to provide a more suitable environment for bacterial activity and thus generate healing products. Therefore, the adjustment of calcium content and pH value in the geopolymer mix design can enhance the effectiveness of MICP crack healing for geopolymer concrete. [ABSTRACT FROM AUTHOR]

Abstract Background Congenital chloride diarrhea (CCD) in a newborn is a rare autosomal recessive disorder with life-threatening complications, requiring early diagnostics and treatment to prevent severe dehydration and infant mortality. SLC26A3 rs386833481 (c.392C>G; p.P131R) gene polymorphism is an important genetic determinant of CCD. Here, we report the influence of the non-synonymous SLC26A3 variant rs386833481 gene polymorphism on the function of the epithelial barrier and the potential mechanisms of these effects. Results We found that P131R-SLC26A3 increased dysfunction of the epithelial barrier compared with wild type SLC26A3 in human colonic Caco-2 and mouse colonic CMT-93 cells. When P131R-SLC26A3 was subsequently reverted to wild type, the epithelial barrier function was restored similar to wild type cells. Further study demonstrated that variant P131R-SLC26A3 disrupts function of epithelial barrier through two distinct molecular mechanisms: (a) decreasing SLC26A3 expression through a ubiquitination pathway and (b) disrupting a key interaction with its partner ZO-1/CFTR, thereby increasing the epithelial permeability. Conclusion Our study provides an important insight of SLC26A3 SNPs in the regulation of the epithelial permeability and indicates that SLC26A3 rs386833481 is likely a causative mutation in the dysfunction of epithelial barrier of CCD, and correction of this SNP or increasing SLC26A3 function could be therapeutically beneficial for chronic diarrhea diseases.

This paper presents experimental investigations into the effects of ultrafine blast furnace slag on microstructure improvements against chloride penetration in saturated and unsaturated cementitious systems exposed to cyclic drying–wetting conditions. The hydration kinetics of ultrafine slag powders and pore solution chemistry in slag-blended cementitious systems at different ages, together with the main hydration products and pore structure characteristics, were determined. The chloride profiles accounting for different slag contents and drying–wetting cycles were measured. The results reveal that the reactivity of ultrafine slag can be well described with Avrami’s equation. The dilution effect of the slag predominated the pore solution chemistry, and the pH value decreased with a higher inclusion of slag. An optimal inclusion of 65% slag by mass of the binder corresponding to the finest pore structure and highest hydrotalcite content was found, which provides a reasonable basis for the slow chloride diffusion and high chloride binding. Under drying–wetting exposure, the specimen with a lower saturation exhibited a higher chloride transport caused by capillary absorption in the skin layer. The chloride transport tended to be diffusion controlled after sufficient drying–wetting cycles.

The regulation of luminal ion concentrations is critical for the function of, and transport between intracellular organelles. The importance of the acidic pH in the compartments of the endosomal-lysosomal pathway has been well-known for decades. Besides the V-ATPase, which pumps protons into their lumen, a variety of ion transporters and channels is involved in the regulation of the organelles' complex ion homeostasis. Amongst these are the intracellular members of the CLC family, ClC-3 through ClC-7. They localize to distinct but overlapping compartments of the endosomal-lysosomal pathway, partially with tissue-specific expression. Functioning as 2Cl−/H+ exchangers, they can support the vesicular acidification and accumulate luminal Cl−. Mutations in the encoding genes in patients and mouse models underlie severe phenotypes including kidney stones with CLCN5 and osteopetrosis or hypopigmentation with CLCN7. Dysfunction of those intracellular CLCs that are expressed in neurons lead to neuronal defects. Loss of endosomal ClC-3, which heteromerizes with ClC-4, results in neurodegeneration. Mutations in ClC-4 are associated with epileptic encephalopathy and intellectual disability. Mice lacking the late endosomal ClC-6 develop a lysosomal storage disease with reduced pain sensitivity. Human gene variants have been associated with epilepsy, and a gain-of-function mutation causes early-onset neurodegeneration. Dysfunction of the lysosomal ClC-7 leads to a lysosomal storage disease and neurodegeneration in mice and humans. Reduced luminal chloride, as well as altered calcium regulation, has been associated with lysosomal storage diseases in general. This review discusses the properties of endosomal and lysosomal Cl−/H+ exchange by CLCs and how various alterations of ion transport by CLCs impact organellar ion homeostasis and function in neurodegenerative disorders.

Neuronal intracellular chloride concentration ([Cl−]i) is a crucial determinant of transmission mediated by the γ‐aminobutyric acid type A receptor (GABAAR), which subserves synaptic and extrasynaptic inhibition as well as excitation. The Cl− ion is the main carrier of charge through the GABAAR; however, bicarbonate ions (HCO3-) flowing in the opposite direction can also contribute to the net current. The direction of Cl− and HCO3- fluxes is determined by the underlying electrochemical gradient, which is controlled by Cl− transporters and channels. Accumulating evidence suggests that active mechanisms of chloride transport across the GABAAR pore can underlie the regulation of [Cl−]i. Measurement of Cl−/ HCO3-‐ATPase activity and Cl− transport in HEK 293FT cells expressing homomeric or heteromeric GABAAR ensembles (α2, β3, or γ2) with fluorescent dye for chloride demonstrated that receptor subtypes containing the β3 subunit show enzymatic activity and participate in GABA‐mediated or ATP‐dependent Cl− transport. GABA‐mediated flow of Cl− ions into and out of the cells occurred for a short time period but then rapidly declined. However, Cl− ion flux was stabilized for a long time period in the presence of HCO3- ions. The reconstituted β3 subunit isoform, purified as a fusion protein, confirmed that β3 is critical for ATPase; however, only the triplet variant showed the full receptor function. The high sensitivity of the enzyme to γ‐phosphate inhibitors led us to postulate that the β3 subunit is catalytic. Our discovery of a GABAAR type that requires ATP consumption for chloride movement provides new insight into the molecular mechanisms of inhibitory signaling. [ABSTRACT FROM AUTHOR]

Impressive work has been completed in recent decades on the transmembrane anion transport capability of small synthetic transporters from many different structural classes. However, very few predicting models have been proposed for the fast screening of compound libraries before spending time and resources on the laboratory bench for their synthesis. In this work, a new approach is presented which aims at describing the transport process by taking all the steps into explicit consideration, and includes all possible experiment-derived parameters. The algorithm is able to simulate the macroscopic experiments performed with lipid vesicles to assess the ion-transport ability of the synthetic transporters following a non-electrogenic uniport mechanism. While keeping calculation time affordable, the final goal is the curve-fitting of real experimental data—so, to obtain both an analysis and a predictive tool. The role and the relative weight of the different parameters is discussed and the agreement with the literature is shown by using the simulations of a virtual benchmark case. The fitting of real experimental curves is also shown for two transporters of different structural type.

CLC proteins comprise Cl− channels and anion/H+ antiporters involved in several fundamental physiological processes. ClC-7 is a lysosomal Cl−/H+ antiporter that together with its beta subunit Ostm1 has a critical role in the ionic homeostasis of lysosomes and of the osteoclasts’ resorption lacuna, although the specific underlying mechanism has so far remained elusive. Mutations in ClC-7 cause osteopetrosis, but also a form of lysosomal storage disease and neurodegeneration. Interestingly, both loss-of- and gain-of-function mutations of ClC-7 can be pathogenic, but the mechanistic implications of this finding are still unclear. This review will focus on the recent advances in our understanding of the biophysical properties of ClC-7 and of its role in human diseases with a focus on osteopetrosis and neurodegeneration.

The development of stimuli-responsive artificial H + /Cl - ion channels, capable of specifically disturbing the intracellular ion homeostasis of cancer cells, presents an intriguing opportunity for achieving high selectivity in cancer therapy. Herein, we describe a novel family of non-covalently stapled self-assembled artificial channels activatable by biocompatible visible light at 442 nm, which enables the co-transport of H + /Cl - across the membrane with H + /Cl - transport selectivity of 6.0. Upon photoirradiation of the caged C4F-L for 10 min, 90 % of ion transport efficiency can be restored, giving rise to a 10.5-fold enhancement in cytotoxicity against human colorectal cancer cells (IC 50 =8.5 μM). The mechanism underlying cancer cell death mediated by the H + /Cl - channels involves the activation of the caspase 9 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, C4F-L exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200 μM., (© 2023 Wiley-VCH GmbH.)

Carbonation is one of the factors that can influence the chlorides transport. Despite the combined action of chlorides and carbonation being a reality, there is no consensus on the effect of this coupled deterioration on chloride transport. Accelerated tests were used to simulate this environment. Concrete specimens were cast using 0.60 water/cement ratio and CEM I 42.5R. After curing, half of specimens was submitted to accelerated carbonation test (20ºC, 55% RH and 4% CO2) during 1 and 7 months. The other half was protected with plastic film during the same period. Then, the specimens were submitted to the accelerated chlorides attack using: migration test and immersion test. Finished the immersion test, powder samples were extracted from surface to bulk and analysed to obtain free and total chloride profiles and pH profile. According to migration test results, the carbonation increases chloride transport regardless the test period. According to the immersion test results, there is a decrease in chloride ions transport when the specimens are carbonated for 1 month and a noticeable increase when carbonation period increases to 7 months. The redistribution of pores in carbonated concrete and the difficulty of chlorides binding in carbonated concrete are related to these results.

The chloride-proton exchanger CLC-7 plays critical roles in lysosomal homeostasis and bone regeneration and its mutation can lead to osteopetrosis, lysosomal storage disease and neurological disorders. In lysosomes and the ruffled border of osteoclasts, CLC-7 requires a β-subunit, OSTM1, for stability and activity. Here, we present electron cryomicroscopy structures of CLC-7 in occluded states by itself and in complex with OSTM1, determined at resolutions up to 2.8 Å. In the complex, the luminal surface of CLC-7 is entirely covered by a dimer of the heavily glycosylated and disulfide-bonded OSTM1, which serves to protect CLC-7 from the degradative environment of the lysosomal lumen. OSTM1 binding does not induce large-scale rearrangements of CLC-7, but does have minor effects on the conformation of the ion-conduction pathway, potentially contributing to its regulatory role. These studies provide insights into the role of OSTM1 and serve as a foundation for understanding the mechanisms of CLC-7 regulation.

Durability improvement is always important for steel–concrete structures exposed to chloride salt environment. The present research investigated the influence of a novel nano-precursor inhibiting material (NPI), organic carboxylic acid ammonium salt, on the mechanical and transport properties of concrete. The NPI caused a slight reduction in the strength of concrete at later ages. NPI significantly decreased water absorption and slowed down the speed of water absorption of concrete. In addition, the NPI decreased the charge passed and the chloride migration coefficient, and the results of the natural chloride diffusion showed that the NPI decreased the chloride concentration and the chloride diffusion coefficient. The NPI effectively improved the resistance of chloride penetration into testing concrete. The improvement in the impermeability of concrete was ascribed to the incorporation with the NPI, which resulted in increasing the contact angle of cement pastes. The contact angle went up from 17.8° to 85.8° for 0% and 1.2% NPI, respectively, and cement pastes became less hydrophilic. Some small pore throats were unconnected. Besides, the NPI also optimized the pore size distribution of hardened cement paste.

Despite extensive research on nitrate export and removal, nutrient contamination remains a major threat to water bodies worldwide. At the local scale, nitrate removal is governed by biogeochemical conditions that vary in space and time, making integration to entire landscapes critical. Water transit times have often been used to describe solute transport, but the relation between water age and nitrate removal at the catchment scale is still poorly understood. We test the hypothesis that nitrate removal peaks when the fraction of young water in discharge is at its minimum, because nitrate removal occurs mostly under dry conditions where deeper, older groundwater dominates streamflow. We tested this hypothesis by exploring a detailed water quality record from the Kervidy–Naizin catchment (FR) and comparing the dynamics of nitrate to those of a conservative solute (chloride). We find that estimates of nitrate removal are consistent with previous estimates at the site and they show a good (inverse) correlation with the fraction of streamflow that is younger than 2.5 months. However, this young water fraction cannot be used to predict nitrate removal in the winter–spring period, when no removal is observed regardless of streamflow age. While this leads us to reject our hypothesis during the winter period, it also suggests that water age distributions and their correlation with nitrate removal can possibly reveal distinct sources of stream water at different hydrologic regimes and relevant biogeochemical reactions. [ABSTRACT FROM AUTHOR]

Background: Histamine is a key mediator of the anti-inflammatory activity conferred by the probiotic organism Lactobacillus reuteri ATCC PTA 6475 in animal models of colitis and colorectal cancer. In L. reuteri, histamine synthesis and secretion requires l-histidine decarboxylase and a l-histidine/histamine exchanger. Chloride channel (ClC)-family proton/chloride antiporters have been proposed to act as electrochemical shunts in conjunction with amino acid decarboxylase systems, correcting ion imbalances generated by decarboxylation through fixed ratio exchange of two chloride ions for one proton. This family is unique among transporters by facilitating ion flux in either direction. Here we examine the histidine decarboxylase system in relation to ClC antiporters in the probiotic organism Lactobacillus reuteri. Results: In silico analyses reveal that L. reuteri possesses two ClC transporters, EriC and EriC2, as well as a complete histidine decarboxylase gene cluster (HDC) for the synthesis and export of histamine. When the transport activity of either proton/chloride antiporter is disrupted by genetic manipulation, bacterial histamine output is reduced. Using fluorescent reporter assays, we further show that ClC transporters affect histamine output by altering intracellular pH and membrane potential. ClC transport also alters the expression and activity of two key HDC genes: the histidine decarboxylase (hdcA) and the histidine/histamine exchanger (hdcP). Conclusions: Histamine production is a potentially beneficial feature for intestinal microbes by promoting long-term colonization and suppression of inflammation and host immune responses. ClC transporters may serve as tunable modulators for histamine production by L. reuteri and other gut microbes. [ABSTRACT FROM AUTHOR]

Pendrin (SLC26A4) is an anion exchanger from the SLC26 transporter family which is mutated in human patients affected by Pendred syndrome, an autosomal recessive disease characterized by sensoneurinal deafness and hypothyroidism. Pendrin is also expressed in the kidney where it mediates the exchange of internal HCO3− for external Cl− at the apical surface of renal type B and non-A non-B-intercalated cells. Studies using pendrin knockout mice have first revealed that pendrin is essential for renal base excretion. However, subsequent studies have demonstrated that pendrin also controls chloride absorption by the distal nephron and that this mechanism is critical for renal NaCl balance. Furthermore, pendrin has been shown to control vascular volume and ultimately blood pressure. This review summarizes the current knowledge about how pendrin is linking renal acid-base regulation to blood pressure control. [ABSTRACT FROM AUTHOR]

[Display omitted] • The "stray current induced ITZ effect" was revealed for the first time. • Coupled stray current and hydraulic pressure affected ITZ thickness and porosity. • The increase of ITZ thickness and porosity was mainly attributed to Ca leaching. • Stray current significantly enhanced the ability of chlorides transport through ITZ. Understanding the influence of interface transition zone (ITZ) on chloride migration characteristics in concrete under coupled stray current and high hydraulic pressure is essential to solve the durability problem of ultra-deep buried infrastructures (40 m-100 m). Herein, an advanced test system is developed and the chloride migration characteristics of deeply buried concrete is comprehensively investigated. Specimens were casted with the same aggregate volume content but different aggregate size distribution. The ITZ between aggregate and cement matrix was measured from BSE (back scattered electron imaging) images, and the ITZ thickness was measured by Vickers hardness. The silver nitrate spray was used to determine the chloride migration front, and the effective diffusion coefficient was calculated. The results showed the concentric expansion and overflow method based on BSE images were effective ways to determine ITZ porosity distribution. The significant increase of ITZ thickness and porosity on concrete reaction surface under stray current environment was observed and defined as "stray current induced ITZ effect", which was considered to be the fundamental reason for the distinct differences in chloride migration depth and effective diffusion coefficient of specimens with different aggregate gradations. [ABSTRACT FROM AUTHOR]

• Chlorides diffuse twice as fast in LCK as in an equivalent CEM I concrete. • AAS and SSC concretes are extremely resistant to chloride penetration. • A temperature of 50 °C should be used as preconditioning of slag-based samples. The general transfer properties (water porosity, mercury intrusion porosimetry, water permeability, capillary absorption, gas permeability and resistivity) and chloride penetration resistance (natural chloride diffusion test and rapid chloride permeability test) of three low-carbon concretes C25/30 (low clinker (LCK) concrete, alkali-activated slag with sodium carbonate (Na 2 CO 3 -AAS) concrete and supersulfated cement (SSC) concrete) were evaluated and compared, in order to identify the strengths and weaknesses of each technology. The results show that the LCK concrete is characterized by "excellent" transfer properties (low water porosity, gas permeability, water permeability and capillary absorption) but high viscosity in the fresh state and very high chloride permeability. AAS and SSC concretes have similar transfer properties, comparable to classical concretes C25/30, and are extremely resistant to chloride penetration. Finally, the use of traditional protocols for durability tests applied to alternative low-carbon binders is questioned and metrology adaptations are proposed. [ABSTRACT FROM AUTHOR]

Cement is widely used in marine concrete, and its resistance to chloride ion corrosion has been widely considered. In this paper, based on a laboratory test, the influence of different hydrostatic pressures, coarse aggregate contents and w/c ratios on the chloride resistance performance is analyzed. Based on COMSOL finite element software, a two-dimensional cementitious materials model is established, and the simulation results are compared with the experimental results. The results show that the penetration depth of chloride ions in cement increases with the increase of the w/c ratio. Under the hydrostatic pressure of 0 MPa, when the w/c ratio is 0.35, the penetration depth of chloride ions is 7.4 mm, and the simulation result is 8.0 mm. When the w/c ratio is 0.45, the penetration depth of chloride ions is 9.3 mm, and the simulation result is 9.9 mm. When the w/c ratio is 0.55, the penetration depth of chloride ions is 12.9 mm, and the simulation result is 12.1 mm. Under different hydrostatic pressures, the penetration depth of chloride ions obviously changes, and with the increase in hydrostatic pressure, the penetration depth of chloride ions deepens. Under the w/c ratio of 0.35, when the hydrostatic pressure is 0.5 MPa, the penetration depth of chloride ions is 11.3 mm, and the simulation result is 12.1 mm. When the hydrostatic pressure is 1.0 MPa, the penetration depth of chloride ions is 16.2 mm, and the simulation result is 17.5 mm.

The epithelial anion transporter SLC26A9 contributes to airway surface hydration and gastric acid production. Colocalizing with CFTR, SLC26A9 has been proposed as a target for the treatment of cystic fibrosis. To provide molecular details of its transport mechanism, we present cryo-EM structures and a functional characterization of murine Slc26a9. These structures define the general architecture of eukaryotic SLC26 family members and reveal an unusual mode of oligomerization which relies predominantly on the cytosolic STAS domain. Our data illustrates conformational transitions of Slc26a9, supporting a rapid alternate-access mechanism which mediates uncoupled chloride transport with negligible bicarbonate or sulfate permeability. The characterization of structure-guided mutants illuminates the properties of the ion transport path, including a selective anion binding site located in the center of a mobile module within the transmembrane domain. This study thus provides a structural foundation for the understanding of the entire SLC26 family and potentially facilitates their therapeutic exploitation.

Key points: Potassium‐chloride co‐transporter 2 (KCC2) plays a critical role in regulating chloride homeostasis, which is essential for hyperpolarizing inhibition in the mature nervous system.KCC2 interacts with many proteins involved in excitatory neurotransmission, including the GluK2 subunit of the kainate receptor (KAR).We show that activation of KARs hyperpolarizes the reversal potential for GABA (EGABA) via both ionotropic and metabotropic signalling mechanisms.KCC2 is required for the metabotropic KAR‐mediated regulation of EGABA, although ionotropic KAR signalling can hyperpolarize EGABA independent of KCC2 transporter function.The KAR‐mediated hyperpolarization of EGABA is absent in the GluK1/2−/− mouse and is independent of zinc release from mossy fibre terminals.The ability of KARs to regulate KCC2 function may have implications in diseases with disrupted excitation: inhibition balance, such as epilepsy, neuropathic pain, autism spectrum disorders and Down's syndrome. Potassium‐chloride co‐transporter 2 (KCC2) plays a critical role in the regulation of chloride (Cl−) homeostasis within mature neurons. KCC2 is a secondarily active transporter that extrudes Cl− from the neuron, which maintains a low intracellular Cl− concentration [Cl−]. This results in a hyperpolarized reversal potential of GABA (EGABA), which is required for fast synaptic inhibition in the mature central nervous system. KCC2 also plays a structural role in dendritic spines and at excitatory synapses, and interacts with 'excitatory' proteins, including the GluK2 subunit of kainate receptors (KARs). KARs are glutamate receptors that display both ionotropic and metabotropic signalling. We show that activating KARs in the hippocampus hyperpolarizes EGABA, thus strengthening inhibition. This hyperpolarization occurs via both ionotropic and metabotropic KAR signalling in the CA3 region, whereas it is absent in the GluK1/2−/− mouse, and is independent of zinc release from mossy fibre terminals. The metabotropic signalling mechanism is dependent on KCC2, although the ionotropic signalling mechanism produces a hyperpolarization of EGABA even in the absence of KCC2 transporter function. These results demonstrate a novel functional interaction between a glutamate receptor and KCC2, a transporter critical for maintaining inhibition, suggesting that the KAR:KCC2 complex may play an important role in excitatory:inhibitory balance in the hippocampus. Additionally, the ability of KARs to regulate chloride homeostasis independently of KCC2 suggests that KAR signalling can regulate inhibition via multiple mechanisms. Activation of kainate‐type glutamate receptors could serve as an important mechanism for increasing the strength of inhibition during periods of strong glutamatergic activity. Key points: Potassium‐chloride co‐transporter 2 (KCC2) plays a critical role in regulating chloride homeostasis, which is essential for hyperpolarizing inhibition in the mature nervous system.KCC2 interacts with many proteins involved in excitatory neurotransmission, including the GluK2 subunit of the kainate receptor (KAR).We show that activation of KARs hyperpolarizes the reversal potential for GABA (EGABA) via both ionotropic and metabotropic signalling mechanisms.KCC2 is required for the metabotropic KAR‐mediated regulation of EGABA, although ionotropic KAR signalling can hyperpolarize EGABA independent of KCC2 transporter function.The KAR‐mediated hyperpolarization of EGABA is absent in the GluK1/2−/− mouse and is independent of zinc release from mossy fibre terminals.The ability of KARs to regulate KCC2 function may have implications in diseases with disrupted excitation: inhibition balance, such as epilepsy, neuropathic pain, autism spectrum disorders and Down's syndrome. [ABSTRACT FROM AUTHOR]

Abstract Research on mechanisms of chloride ion transport in cement-based materials is relevant to improve the durability of reinforced concrete structures. Conventional chloride-transport models consider a linear diffusion equation, only valid for fully saturated and non-reactive concrete. This work proposes a model of chloride and other ions penetration in saturated concrete considering diffusion, chloride binding, chemical activity and migration. The model uses intrinsic diffusion coefficients. The influence of the ionic pore solution on chloride penetration into concrete is also studied. Chemical activity is introduced by coupling the transport equations to the Pitzer model. The migration is accounted for by imposing the electro-neutrality condition of the pore solution. It is shown that fitting the well known error function to experimentally obtained chloride profiles present results which are difficult to interpret. Moreover, it is shown that, by accounting for solely diffusion and chloride binding, good results are obtained. Contemplating chemical activity and migration slightly improves such results and allows concentration profiles of the present ionic species in the pore solution to be determined. Such profiles are involved in the degradation processes of cement-based materials exposed to aggressive environments. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The tracer 36Cl−, currently used to measure transepithelial Cl− fluxes, has become prohibitively expensive, threatening its future use. 125Iodide, previously validated alongside 36Cl− as a tracer of Cl− efflux by cells, has not been tested as a surrogate for 36Cl− across epithelia.What is the main finding and its importance?We demonstrate that 125I− can serve as an inexpensive replacement for measuring Cl− transport across mouse large intestine, tracking Cl− transport in response to cAMP stimulation (inducing Cl− secretion) in the presence and absence of the main gastrointestinal Cl−–HCO3− exchanger, DRA. Chloride transport is important for driving fluid secretion and absorption by the large intestine, with dysregulation resulting in diarrhoea‐associated pathologies. The radioisotope 36Cl− has long been used as a tracer to measure epithelial Cl− transport but is prohibitively expensive. 125Iodide has been used as an alternative to 36Cl− in some transport assays but has never been validated as an alternative for tracing bidirectional transepithelial Cl− fluxes. The goal of this study was to validate 125I− as an alternative to 36Cl− for measurement of Cl− transport by the intestine. Simultaneous fluxes of 36Cl− and 125I− were measured across the mouse caecum and distal colon. Net Cl− secretion was induced by the stimulation of cAMP with a cocktail of forskolin (FSK) and 3‐isobutyl‐1‐methylxanthine (IBMX). Unidirectional fluxes of 125I− correlated well with 36Cl− fluxes after cAMP‐induced net Cl− secretion, occurring predominantly through a reduction in the absorptive mucosal‐to‐serosal Cl− flux rather than by stimulation of the secretory serosal‐to‐mucosal Cl− flux. Correlations between 125I− fluxes and 36Cl− fluxes were maintained in epithelia from mice lacking DRA (Slc26a3), the main Cl−–HCO3− exchanger responsible for Cl− absorption by the large intestine. Lower rates of Cl− and I− absorption in the DRA knockout intestine suggest that DRA might have a previously unrecognized role in iodide uptake. This study validates that 125I− traces transepithelial Cl− fluxes across the mouse large intestine, provides insights into the mechanism of net Cl− secretion and suggests that DRA might be involved in intestinal iodide absorption. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Previously uncharacterized ion transport mechanisms targeted in the DIP with RNAseq. • Several voltage-gated, ligand-gated and mechanosensitive channels were detected. • Na+- and H+-dependent reabsorption of solutes "flushed" during fluid secretion. • Cl− secretion mechanisms may be correlated with base recovery. • Response to, processing, and sometimes production of endocrine ligands. Abstract Excretion of metabolic wastes and toxins in insect Malpighian tubules (MTs) is coupled to secretion of ions and fluid. Larval lepidopterans demonstrate a complex and regionalized MT morphology, and recent studies of larvae of the cabbage looper, Trichoplusia ni , have revealed several unusual aspects of ion transport in the MTs. Firstly, cations are reabsorbed via secondary cells (SCs) in T. ni , whereas in most insects SCs secrete ions. Secondly, SCs are coupled to neighbouring principal cells (PCs) via gap junctions to enable such ion reabsorption. Thirdly, PCs in the SC-containing distal ileac plexus (DIP) region of the tubule reverse from cation secretion to reabsorption in response to dietary ion loading. Lastly, antidiuresis is observed in response to a kinin neuropeptide, which targets both PCs and SCs, whereas in most insects kinins are diuretics that act exclusively via SCs. Recent studies have generated a basic model of ion transport in the DIP of the larval T. ni. RNAseq was used to elucidate previously uncharacterised aspects of ion transport and endocrine regulation in the DIP, with the aim of painting a composite picture of ion transport and identifying putative regulatory mechanisms of ion transport reversal in this tissue. Results indicated an overall expression of 9103 transcripts in the DIP, 993 and 382 of which were differentially expressed in the DIP of larvae fed high-K+ and high-Na+ diets respectively. Differentially expressed transcripts include ion-motive ATPases, ion channels and co-transporters, aquaporins, nutrient and xenobiotic transporters, cell adhesion and junction components, and endocrine receptors. Notably, several transcripts for voltage-gated ion channels and cell volume regulation-associated products were detected in the DIP and differentially expressed in larvae fed ion-rich diet. The study provides insights into the transport of solutes (sugars, amino acids, xenobiotics, phosphate and inorganic ions) by the DIP of lepidopterans. Our data suggest that this region of the MT in lepidopterans (as previously reported) transports cations, fluid, and xenobiotics/toxic metals. Besides this, the DIP expresses genes coding for the machinery involved in Na+- and H+-dependent reabsorption of solutes, chloride transport, and base recovery. Additionally, many of the transcripts expressed by the DIP a capacity of this region to respond to, process, and sometimes produce, neuropeptides, steroid hormones and neurotransmitters. Lastly, the DIP appears to possess an arsenal of septate junction components, differential expression of which may indicate junctional restructuring in the DIP of ion-loaded larvae. [ABSTRACT FROM AUTHOR]

Highlights • A prediction model for chloride transport in unsaturated concrete was proposed. • A new device was developed to simulate marine tidal and splash zones. • The chloride content in concrete under drying-wetting cycles was measured. • Numerical simulation and tests of moisture and chloride transport were carried out. Abstract Based on the establishment of a moisture transport model, a prediction model for chloride transport in unsaturated concrete was developed. The moisture transport model considers both the diffusion of water vapor and seepage of liquid water in concrete under drying-wetting conditions. The moisture transport model was verified by wetting and drying tests. In the transport model of chloride ions, both diffusion and convection were considered. Tests of specimens under drying-wetting cycles with four types of cycles were carried out to verify the chloride transport model. Furthermore, a new device was developed to mimic tidal and splash zones of a marine environment to achieve different time ratios of drying-wetting. The measured results of chloride content corresponded with the simulated results. The results showed that the chloride content in concrete displayed no relationship with the ratio of drying and wetting times. The chloride content of concrete in mimicked tidal and splash zones significantly varied with height, especially in the surface layer of concrete, and the chloride content of concrete at the junction of the splash and tidal zones was the highest. [ABSTRACT FROM AUTHOR]

Highlights • A review and statistical meta-analysis of chloride transport in AACs is presented. • The role of Ca2+ in glassy/non-glassy phases within precursors is elucidated. • Higher Si:Al, Na:Al, and heat-curing, in general, improve chloride resistance. • Limitations of current chloride transport measurement techniques are addressed. • Research needs concerning chloride durability of AACs are identified and discussed. Abstract In this review, we present a meta-analysis of experimental data concerning chloride transport in alkali-activated cement (AAC) paste, mortar, and concrete. Sixty-six (66) studies were reviewed with a primary focus on measurement methodology, mixture design, and process-structure-property relationships related to microstructural development (i.e., porosity, pore size distribution), chloride diffusion, and chloride binding. In general, this review elucidates that aluminosilicate precursors with high amorphous contents and increased fineness that are activated with solutions of high alkalinity (Na:Al ≥ 0.75) and silica content (Si:Al ≥ 1.5) in combination with heat-curing (>40 °C) lead to microstructural characteristics (e.g., binder gel chemistries) that improve chloride durability, even though interactions between these factors are not well understood. Descriptive statistics of reported AAC paste porosities and AAC concrete chloride diffusion coefficients by aluminosilicate precursor (i.e., fly ash, slag, calcined clay, natural clay, binary blends) are presented, along with a summative discussion regarding new opportunities for advancing current scientific understanding of chloride transport in AACs. [ABSTRACT FROM AUTHOR]

• Reusing thermoactivated construction waste spoil (CSP) as a binder for durable concrete. • Effects of thermoactivated CSP content and particle size on the chloride transport in concrete. • Combine use of thermoactivated CSP and active admixture for more durable concrete. 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. [ABSTRACT FROM AUTHOR]

• Revealing the coupling effects on chloride ion transport caused by carbonation, FT cycles, loading states and levels, temperature, and saturation. • Modelling essentially the chloride ion transport under the coupling effects of carbonation, FT cycles, loading states and levels, temperature, relative humidity, saturation and concrete deterioration. • Revealing the degradation laws of flexural capacity of the multi-factor corroded beams. 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. [ABSTRACT FROM AUTHOR]

The recycling technology of construction and demolition wastes is an inevitable choice towards the sustainable development of the construction industry, aiming at addressing the problems of raw materials shortage and waste disposal. The utilization of recycled coarse aggregate (RCA) in new concrete production has been identified as an effective way to reasonable application of natural resources replacement and environmental preservation. In service, external mechanical loading can easily cause the initiation and interconnectivity of microcracks inside concrete, specifically the complex multiple interface structures of recycled aggregate concrete (RAC) due to the old adhered mortar at the surface of RCAs, which can remarkably accelerate the process of water penetration and aggressive ions penetration into concrete. Thus, knowledge of mass transport properties in the loading-induced damaged RAC contributes to the durability evaluation of RAC and its extensive application in the practical engineering. This paper reviews the previous findings on the mechanical loading effects on the chloride transport properties of RAC. The effects of loading-induced damage on microstructure evolution of RAC as well as the damage characteristics were discussed. The research progress on the chloride ingress behavior of RAC subjected to mechanical loading was highlighted from the viewpoint of testing method, loading devices and numerical calculation, and the modified effects on the transport properties were further analyzed. On this basis, the future research on the durability-related properties of RAC would be finally proposed, which is helpful to further perfect theoretical development and technological innovation of RAC durability in the aggressive environment. [ABSTRACT FROM AUTHOR]

Chloride-induced steel corrosion is the most concerning issue for the durability of concrete structures. Concrete and steel samples were obtained from a 30-year-old reinforced concrete bridge. The chloride content was measured by a potentiometric titration method and the microstructure of concrete was obtained by scanning electron microscopy and mercury intrusion porosimetry. The rust phases of the steel were detected by X-ray diffraction and Raman analysis. It was found that the convection depth for chloride transport in cracked concrete was significantly larger than that in uncracked concrete. The concrete in a pier column facing upstream had greater porosity due to the water impact and calcium leaching. The coefficients of variability of chloride diffusivity of concrete for the bridge deck and the pier column were significantly different. Rust phases including lepidocrocite, goethite, akaganeite, magnetite, and maghemite were detected using Raman spectroscopy and X-ray diffraction. The major phases of steel rust in the atmospheric zone were lepidocrocite and goethite, while they were lepidocrocite and maghemite in the tidal zone. The results of this study would provide information concerning the chloride-induced steel corrosion under a marine environment in order to predict long-term behaviors of a reinforced concrete structure.

We performed steered molecular dynamics (SMD) and umbrella sampling simulations of Cl− ion migration through the transmembrane domain of a prototypical E. coli CLC Cl−/H+ antiporter by employing combined quantum-mechanical (QM) and molecular-mechanical (MM) calculations. The SMD simulations revealed interesting conformational changes of the protein. While no large-amplitude motions of the protein were observed during pore opening, the side chain rotation of the protonated external gating residue Glu148 was found to be critical for full access of the channel entrance by Cl−. Moving the anion into the external binding site (Sext) induced small-amplitude shifting of the protein backbone at the N-terminal end of helix F. As Cl− traveled through the pore, rigid-body swinging motions of helix R separated it from helix D. Helix R returned to its original position once Cl− exited the channel. Population analysis based on polarized wavefunction from QM/MM calculations discovered significant (up to 20%) charge loss for Cl− along the ion translocation pathway inside the pore. The delocalized charge was redistributed onto the pore residues, especially the functional groups containing π bonds (e.g., the Tyr445 side chain), while the charges of the H atoms coordinating Cl− changed almost negligibly. Potentials of mean force computed from umbrella sampling at the QM/MM and MM levels both displayed barriers at the same locations near the pore entrance and exit. However, the QM/MM PMF showed higher barriers (~10 kcal/mol) than the MM PMF (~2 kcal/mol). Binding energy calculations indicated that the interactions between Cl− and certain pore residues were overestimated by the semi-empirical PM3 Hamiltonian and underestimated by the CHARMM36 force fields, both of which were employed in the umbrella sampling simulations. In particular, CHARMM36 underestimated binding interactions for the functional groups containing π bonds, missing the stabilizations of the Cl− ion due to electron delocalization. The results suggested that it is important to explore these quantum effects for accurate descriptions of the Cl− transport.

Clostridium difficile infection (CDI) is the primary cause of nosocomial diarrhea in the United States. Although C. difficile toxins A and B are the primary mediators of CDI, the overall pathophysiology underlying C. difficile-associated diarrhea remains poorly understood. Studies have shown that a decrease in both NHE3 (Na+/H+ exchanger) and DRA (downregulated in adenoma, Cl -/HCO3- exchanger), resulting in decreased electrolyte absorption, is implicated in infectious and inflammatory diarrhea. Furthermore, studies have shown that NHE3 is depleted at the apical surface of intestinal epithelial cells and downregulated in patients with CDI, but the role of DRA in CDI remains unknown. In the current studies, we examined the effects of C. difficile toxins TcdA and TcdB on DRA protein and mRNA levels in intestinal epithelial cells (IECs). Our data demonstrated that DRA protein levels were significantly reduced in response to TcdA and TcdB in IECs in culture. This effect was also specific to DRA, as NHE3 and PAT-1 (putative anion transporter 1) protein levels were unaffected by TcdA and TcdB. Additionally, purified TcdA and TcdA + TcdB, but not TcdB, resulted in a decrease in colonic DRA protein levels in a toxigenic mouse model of CDI. Finally, patients with recurrent CDI also exhibited significantly reduced expression of colonic DRA protein. Together, these findings indicate that C. difficile toxins markedly downregulate intestinal expression of DRA which may contribute to the diarrheal phenotype of CDI. NEW & NOTEWORTHY Our studies demonstrate, for the first time, that C. difficile toxins reduce DRA protein, but not mRNA, levels in intestinal epithelial cells. These findings suggest that a downregulation of DRA may be a critical factor in C. difficile infection-associated diarrhea. [ABSTRACT FROM AUTHOR]

The chloride transport behavior of fly ash blended cement material was investigated in this study by using electrochemical impedance spectroscopy (EIS). The chloride penetration was studied by means of EIS. A new equivalent circuit model was applied to describe the electrochemical system of fly ash blended cementitious materials. Experimental results demonstrate that the increase in the fly ash replacement ratio of sample can increase the penetration depth of chloride ion. In addition, the increase in the fly ash replacement ratio of sample can enlarge the Nyquist curve semi-circle, and improve ion transfer resistance at the solid-liquid phase interface. We determined the quantitative relationship between electrochemical properties and chloride penetration depth in order to successfully predict the chloride ion penetration depth of blended cements with varying fly ash content. It is expected to complement the existing test standards regarding the durability evaluation of construction materials. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? The aim was to investigate the roles of extracellular chloride in electrical slow waves and resting membrane potential of mouse jejunal smooth muscle by replacing chloride with the impermeant anions gluconate and isethionate., What is the main finding and its importance? The main finding was that in smooth muscle cells, the resting Cl− conductance is low, whereas transmembrane Cl− movement in interstitial cells of Cajal (ICCs) is a major contributor to the shape of electrical slow waves. Furthermore, the data confirm that ICCs set the smooth muscle membrane potential and that altering Cl− homeostasis in ICCs can alter the smooth muscle membrane potential., Intracellular Cl− homeostasis is regulated by anion-permeable channels and transporters and contributes to excitability of many cell types, including smooth muscle and interstitial cells of Cajal (ICCs). Our aims were to investigate the effects on electrical activity in mouse jejunal muscle strips of replacing extracellular Cl− (Cl−o) with the impermeant anions gluconate and isethionate. On reducing Cl−o, effects were observed on electrical slow waves, with small effects on smooth muscle membrane voltage ( Em). Restoration of Cl− hyperpolarized smooth muscle Em proportional to the change in Cl−o concentration. Replacement of 90% of Cl−o with gluconate reversibly abolished slow waves in five of nine preparations. Slow waves were maintained in isethionate. Gluconate and isethionate substitution had similar concentration-dependent effects on peak amplitude, frequency, width at half peak amplitude, rise time and decay time of residual slow waves. Gluconate reduced free ionized Ca2+ in Krebs solutions to 0.13 m m. In Krebs solutions containing normal Cl− and 0.13 m m free Ca2+, slow wave frequency was lower, width at half peak amplitude was smaller, and decay time was faster. The transient hyperpolarization following restoration of Cl−o was not observed in W/Wv mice, which lack pacemaker ICCs in the small intestine. We conclude that in smooth muscle cells, the resting Cl− conductance is low, whereas transmembrane Cl− movement in ICCs plays a major role in generation or propagation of slow waves. Furthermore, these data support a role for ICCs in setting smooth muscle Em and that altering Cl− homeostasis in ICCs can alter smooth muscle Em. [ABSTRACT FROM AUTHOR]

• Pore structure of macro-synthetic fiber reinforced concrete. • Analysis of pore structure based on image processing. • Quantitative characterization of pore structure complexity and uniformity. • Quantitative relation between macroscopic properties and pore structure. This study proposes a method for the quantitative characterization of the complexity and uniformity of pore structure, and explores the effect of macro-synthetic fiber inclusion on the shear resistance and chloride transport of concrete from the perspective of pore structure. First, the shear capacity and chloride migration coefficient of normal concrete and macro-synthetic fiber reinforced concrete with fiber content of 3, 4.5, 6, and 9 kg/m3 were tested. Next, the porosity and pore size distribution were determined using the Rapidair 457 pore structure analyzer. The complexity of the pore structure was quantified using the fractal dimension calculated from the pore structure scans. The uniformity of spatial distribution of pores was quantified by the standard deviation of pore frequency. The results showed that increasing the fiber content increased the shear resistance and chloride transport of concrete while increasing the complexity and uniformity of pore structure. High-fidelity correlations between shear resistance and pore structure uniformity, chloride transport and pore structure complexity were established. This study will promote the fundamental understanding of concrete pore structure and properties for the development of high-performance fiber reinforced concrete. [ABSTRACT FROM AUTHOR]

Alkali-activated binders for concrete composites are emerging as the available low-embodied-carbon alternatives to ordinary Portland cement (OPC). Despite decades of research, the durability of alkali-activated concrete remains a concern, especially the issues related to chloride penetration and the potential for chloride-induced corrosion of embedded steel bars. In this study, a multi-phase, multi-component ionic numerical model is developed to investigate the chloride transport in alkali-activated fly ash/slag (AAFS) concretes. The model framework considers the porosity of concrete, the chloride binding, and the electrochemical coupling between multi-species. Based on the proposed model, the parametric studies of a series of influencing factors on both chloride transport and initiation time of reinforcement corrosion are performed and discussed. The results indicate that the slag content and the water to binder ratio are the dominant factors affecting chloride penetration and corrosion initiation time of steel bars in AAFS concretes due to their greater contributions to reduce the porosity, while the aggregate volume fraction presents a limited effect compared with other factors. The transport model proposed in this study brings insights to the prediction of the service life of alkali-activated reinforced concrete structures. • A multi-phase, multi-species model is developed to investigate the chloride transport behaviour in the binary AAFS system. • The proposed model considers the porosity of concrete, chloride binding and electrochemical coupling between multi-species. • The influence mechanism of relevant factors on both chloride penetration and reinforcement corrosion onset is discussed. • Slag content is proved to be the most important influencing factor on chloride transport in AAFS concretes. [ABSTRACT FROM AUTHOR]