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Colistin is commonly regarded as the "last-resort" antibiotic for combating life-threatening infections caused by multidrug-resistant (MDR) gram-negative bacteria. Neurotoxicity is a potential adverse event associated with colistin application in clinical settings, yet the exact molecular mechanisms remain unclear. This study examined the detrimental impact of colistin exposure on PC12 cells and the associated molecular mechanisms. Colistin treatment at concentrations of 0–400 μM decreased cell viability and induced apoptotic cell death in both time- and concentration-dependent manners. Exposure to colistin triggered the production of reactive oxygen species (ROS) and caused oxidative stress damage in PC12 cells. N-acetylcysteine (NAC) supplementation partially mitigated the cytotoxic and apoptotic outcomes of colistin. Evidence of mitochondrial dysfunction was observed through the dissipation of membrane potential. Additionally, colistin treatment upregulated the expression of AhR and CYP1A1 mRNAs in PC12 cells. Pharmacological inhibition of AhR (e.g., using α-naphthoflavone) or intervention with the CYP1A1 gene significantly decreased the production of ROS induced by colistin, subsequently lowering caspase activation and cell apoptosis. In conclusion, our findings demonstrate, for the first time, that the activation of the AhR/CYP1A1 pathway contributes partially to colistin-induced oxidative stress and apoptosis, offering insights into the cytotoxic effects of colistin. [ABSTRACT FROM AUTHOR]

In this paper, four water–binder ratios (w/b) of 0.29, 0.33, 0.39, and 0.46 were designed. A variable test temperature was implemented in the drying–wetting cycle test according to the temperature fluctuations in the actual service environment, and the constant temperature test was established as the control group. The mechanical properties and chloride corrosion resistance of concrete with different w/b ratios under variable temperature drying–wetting cycles, as well as the microstructure changes, phase composition, and damage mechanism inside the concrete, were investigated. The results showed that the mechanical properties of concrete increased first and then decreased with drying–wetting cycles increasing, whereas the chloride corrosion resistance continued to decline. A higher w/b exacerbated the deterioration of the concrete performance. A higher w/b increased the porosity, chloride diffusion depth, and chloride content, thus reducing the resistance of chloride corrosion. Compared with w/b = 0.29, the compressive strength, splitting tensile strength, mass, and relative dynamic elasticity modulus of w/b = 0.46 exposed to 60 drying–wetting cycles decreased by 54.50%, 52.44%, 0.96%, and 6.50%, respectively, while the porosity, peak chloride content, and erosion depth increased by 45.12%, 70.45%, and 45.00%. Compared with the drying–wetting cycle with a constant temperature, the cumulative damage caused by the drying–wetting cycle with a variable temperature was greater, resulting in more severe deterioration of concrete performance. The increase in the test temperature significantly accelerated the diffusion rate, penetration depth, and chemical binding capacity of chloride ions. After 60 drying–wetting cycles, the peak chlorine content and erosion depth of w/b = 0.46 under variable temperature cycles were 15.38% and 10.32% higher than those under a constant temperature, while the compressive strength, splitting tensile strength, mass, and relative dynamic elastic modulus were reduced by 7.76%, 14.81%, 0.33%, and 2.40%, respectively. Microscopic analysis confirmed that higher w/b and variable temperature cycles accelerated the decay of mechanical properties and the decline of chloride corrosion resistance. According to the numerical fitting analysis, the w/b should be 0.29~0.39 under the condition that the mechanical properties and chloride corrosion resistance of concrete are met. [ABSTRACT FROM AUTHOR]

Geopolymer concrete (GPC) represents an innovative green and low-carbon construction material, offering a viable alternative to ordinary Portland cement concrete (OPC) in building applications. However, existing studies tend to overlook the recyclability aspect of GPC for future use. Various structural applications necessitate the use of concrete with distinct strength characteristics. The recyclability of the parent concrete is influenced by these varying strengths. This study examined the recycling potential of GPC across a spectrum of strength grades (40, 60, 80, and 100 MPa, marked as C40, C60, C80, and C100) when subjected to freeze–thaw conditions. Recycling 5–16 mm recycled geopolymer coarse aggregate (RGAs) from GPC prepared from 5 to 16 mm natural coarse aggregates (NAs). The cementitious material comprised 60% metakaolin and 40% slag, with natural gravel serving as the NAs, and the alkali activator consisting of sodium hydroxide solution and sodium silicate solution. The strength of the GPC was modulated by altering the Na/Al ratio. After 350 freeze–thaw cycles, the GPC specimens underwent crushing, washing, and sieving to produce RGAs. Subsequently, their physical properties (apparent density, water absorption, crushing index, and attached mortar content and microstructure (microhardness, SEM, and XRD) were thoroughly examined. The findings indicated that GPC with strength grades of C100, C80, and C60 were capable of enduring 350 freeze–thaw cycles, in contrast to C40, which did not withstand these conditions. RGAs derived from GPC of strength grades C100 and C80 complied with the criteria for Class II recycled aggregates, whereas RGAs produced from GPC of strength grade C60 aligned with the Class III level. A higher-strength grade in the parent concrete correlated with enhanced performance characteristics in the resulting recycled aggregates. [ABSTRACT FROM AUTHOR]

Nano-SiO2 (NS) is widely used in cement-based materials due to its excellent physical properties. To study the influence of NS content on a cement paste and the interfacial transition zone (ITZ), cement paste samples containing nano content ranging from 0 to 2% (by weight of cement) were prepared, and digital image correlation (DIC) technology was applied to test the mechanical properties. Finally, the optimal NS content was obtained with statistical analysis. The mini-slump cone test showed that, with the help of superplasticizer and ultrasonic treatment, the flowability decreased continuously, as the NS content increased. The DIC experimental results showed that NS could effectively improve the mechanical properties of the cement paste and the ITZ. Specifically, at the content level of 1%, the elastic modulus of cement paste and ITZ was 20.95 GPa and 3.20 GPa, respectively. When compared to that without nanomaterials, the increased amplitude was 73.50% and 90.50%, respectively. However, with the further increase in NS content, the mechanical properties decreased, which was mainly caused by the agglomeration of nanomaterials. Additionally, the NS content did not exhibit a significant effect on the thickness of the ITZ, and its value was maintained at 76.91–91.38 μm. SEM confirmed that NS would enhance the microstructure of both cement paste and ITZ. [ABSTRACT FROM AUTHOR]

Powdery mildew (PM) is the main disease that afflicts bottle gourd. Previous studies on PM mainly focused on its effects on pumpkin, melon, and other crops; however, the exact molecular mechanism of bottle gourd resistance to PM remains unclear. RNA sequencing (RNA-Seq) technology was used to investigate the dynamic changes in leaf transcriptome profiles between resistant and susceptible gourd at 12, 24, 48, and 72 h post-inoculation with powdery mildew. Compared with a susceptible variety (G3), the expression levels of the differentially expressed genes of phenylpropanoid biosynthesis, starch, and sucrose metabolism, and plant–pathogen interaction pathways in disease-resistant plants were upregulated. We propose that disease resistance and tolerance in bottle gourd are enhanced via several pathways, including the antioxidant system, phenylalanine biosynthesis, and cell wall cellulose synthesis. Our research will provide an important basis for further screening and breeding PM resistance in bottle gourd. [ABSTRACT FROM AUTHOR]

Recycled fine aggregate (RFA) produced from concrete waste is commonly used in the construction industry; however, its use for structural concrete members has not been extensively studied. Moreover, its durability in a drying–wetting cycle environment still needs to be examined. In this study, the intrusion process of chloride in concrete under the drying–wetting cycles is experimentally characterized. Chloride penetration tests are carried out on concrete with the incorporation of different RFA replacement rates and mineral admixtures (i.e., fly ash and silica fume). The results show that the chloride penetration of recycled fine aggregate concrete (RFAC) is dependent upon the performance of the concrete itself, while the deterioration of chloride ion erosion resistance is due to the combined action of the replacement rate of RFA and the drying–wetting cycles. The incorporation of RFA degrades the properties of RFAC owing to its drawbacks in the degradation of interfacial properties of RFAC. Exposure to the drying–wetting cycle environment causes the content of free chloride ions in RFAC to increase initially before decreasing with the erosion depth, thereby showing an obvious convection zone and diffusion zone. The incorporation of the mineral admixture can effectively improve the compactness of the concrete microstructure and make concrete less susceptible to chloride ions ingress. RFAC mixed with 15% fly ash and 10% silica fume has a comparable resistance to chloride penetration as a natural aggregate concrete, which is a feasible method for the application of RFA. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that the ACTL6B monoallelic variant is responsible for an autosomal dominant inherited intellectual developmental disorder with severe speech and ambulation deficits. The clinical phenotype of developmental and epileptic encephalopathy type 76 (DEE76) due to ACTL6B biallelic variants was first reported in 2019, with an autosomal recessive mode of inheritance. In this paper, we report on a child in China with DEE76 caused by a compound heterozygous variant of the ACTL6B gene, and we review the literature on ACTL6B gene variants causing DEE76 with complete clinical information. Including our case 1, the genotype and phenotypic characteristics of 18 children from 14 families are summarized. All 18 cases are autosomal recessive, including 12 with homozygous variants and six with compound heterozygous variants. A total of 17 variants have been reported so far, including 14 variants of the loss function. We summarize the clinical features using Human Phenotype Ontology (HPO) terms. We find that DEE76, caused by the ACTL6B biallelic variant, is an early-onset drug-refractory epilepsy with global developmental delayHP:0001263, hypertoniaHP:0001276, and microcephalyHP:0000252, and imaging is characterized by brain delayed myelinationHP:0012448. Our case of DEE76 had not been reported when the patient underwent genetic testing in 2018, and the diagnosis was clarified by the reanalysis of the data 2 years later, being the first reported Chinese patient and the only one in which the application of a ketogenic diet for antiepileptic treatment may have been effective. [ABSTRACT FROM AUTHOR]

Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic CHD2 variants. While only a few pathogenic CHD2 variants have been reported with detailed clinical phenotypes, most of which lack molecular analysis. In this study, next-generation sequencing (NGS) was performed to identify likely pathogenic CHD2 variants in patients with epilepsy. Three likely pathogenic variants were finally identified in different patients. The seizure onset ages were from two years to six years. Patients 1 and 2 had developmental delays before epilepsy, while patient 3 had intellectual regression after the first seizure onset. The observed seizures were myoclonic, febrile, and generalized tonic-clonic, which had been controlled by different combinations of antiepileptic drugs. Two de novo (c.1809_1809+1delGGinsTT, p.? and c.3455+2_3455+3insTG, p.?) and one maternal (c.3783G>A, p.W1261*) variant were identified, which were all predicted to be pathogenic/likely pathogenic. Molecular analysis was performed in patient 1, and we detected aberrantly spliced products, proving the pathogenicity of this CHD2 variant. New cases with novel variants, along with a detailed clinical and molecular analysis, are important for a better understanding of CHD2-related epileptic encephalopathy. [ABSTRACT FROM AUTHOR]

Construction and demolition wastes (C&DWs) have raised a large number of ecological and environmental problems. Recycling C&DWs into arecycled concrete aggregate (RCA) will help save natural resources effectively and reduce the negative impact of C&DW on the environment. Innovative pervious concrete (IPC) can mitigate extreme weather disasters, such as rainstorms, and overcome the low strength and poor durability of traditional pervious concrete. In this study, innovative recycled pervious concrete (IRPC) is prepared by combining RCA with IPC, which has broad application prospects and ecological friendliness. This study investigates the effect of RCA quality grades and replacement rates on the mechanical property, permeability, sulfate resistance and abrasion resistance of IRPC. IRPC mixtures were prepared with three different quality grades (high, medium and low qualities) of aggregates named as NA, RCA1 and RCA2. Moreover, the replacement rate of RCA for NA varied as 0%, 25%, 50%, 75% and 100%. The IRPC specimens were tested for compressive strength, mass loss and abrasion resistance after different sulfate wetting-drying cycles of 0, 30 and 60. The results exhibited that the initial compressive strength of all types of IRPC was more than 40 MPa. The compressive strength and mass of most IRPC increased first and then decreased slightly with the passage of a number of sulfate wetting-drying cycles, indicating IRPC has good resistance to sulfate attack. Sulfate attack and the addition of RCA will reduce the abrasion resistance of IRPC. However, when the replacement rate is lower than 50%, and the RCA quality is better (attached mortar content < 25%), the abrasion resistance of IRPC will be improved under sulfate attack. The experimental results might be useful as a reference and design methodology for employing IRPC in pavement applications in the future. [ABSTRACT FROM AUTHOR]

Multiple recycling of waste concrete has attracted widespread attention. This study presented the carbonation behavior of repeatedly recycled aggregate concrete (RRAC) used in a micro-frozen region. The effects of freeze–thaw cycles on the carbonation depth of three generations of RRAC with 25%, 75%, and 100% of replacement rate were evaluated. All RRAC specimens after different numbers of freeze–thaw cycles were rapidly carbonated for 28 d indoors to test the carbonation resistance of concrete. The results suggested that the carbonation depth of RRAC subjected to freeze–thaw cycles is higher than that in the non-freeze–thaw condition. This is because the freeze–thaw damages cause the internal structure of RRAC to become porous and and prone to cracking, thus providing convenient channels for CO2 to react with the alkali in the cementitious materials. With the growth of replacement rate or recycling number, RRAC reveals serious freeze–thaw damage and inferior carbonation resistance, which is due to the continuous deterioration repeatedly recycled concrete aggregate (RRCA) quality. However, when the replacement rate was 25%, the carbonation depth for the third generation of RAC was comparable to the second generation of RAC at a 75% replacement rate, and even the first generation of 100% RAC. To ensure better carbonation resistance durability of multiple recycling RAC, the low replacement rate of RRCA should be considered. For the third generation of RAC with the 100% replacement rate, its highest carbonation depth after freeze–thaw cycles was 9.16 mm, which still met the design requirements for structural use in a micro-frozen region. This indicates that it is feasible for three generations of RRAC to be used in the micro-frozen environment and that RRAC has great engineering application potential and promotional value. [ABSTRACT FROM AUTHOR]

In this study, the shrinkage performance of recycled aggregate thermal insulation concrete (RATIC) with added glazed hollow beads (GHB) was investigated and a time-dependent shrinkage model was proposed. Two types of recycled fine aggregate (RFA) were used to replace natural fine aggregate in RATIC: RFA from waste concrete (RFA1) and waste clay brick (RFA2). Besides, the mechanical properties and thermal insulation performance of RATIC were also studied. Results showed that the pozzolanic reaction caused by RFA2 effectively improved the mechanical properties of RATIC; 75% was the optimal replacement ratio of RATIC prepared by RFA2. Added RFA decreased the thermal conductivity of thermal insulation concrete (TIC). The total shrinkage strain of RATIC increased with the increase of the replacement ratio of RFA. The 150d total shrinkage of RATIC prepared by RFA1 was 1.46 times that of TIC and the 150d total shrinkage of RATIC prepared by RFA2 was 1.23 times. The addition of GHBs led to the increase of early total shrinkage strain of concrete. Under the combined action of the higher elastic modulus of RFA2 and the pozzolanic components contained in RFA2, the total shrinkage strain of RATIC prepared by RFA2 with the same replacement ratio was smaller than that of RATIC prepared by RFA1. For example, the final total shrinkage strain of RATIC prepared by RFA2 at 100% replacement ratio was about 18.6% less than that of RATIC prepared by RFA1. A time-dependent shrinkage model considering the influence of the elastic modulus of RFA and the addition of GHB on the total shrinkage of RATIC was proposed and validated by the experimental results. [ABSTRACT FROM AUTHOR]

Carbonation durability is an important subject for recycled coarse aggregate concrete (RAC) applied to structural concrete. Extensive studies were carried out on the carbonation resistance of RAC under general environmental conditions, but limited researches investigated carbonation resistance when exposed to chloride ion corrosion, which is an essential aspect for reinforced concrete materials to be adopted in real-world applications. This paper presents a study on the carbonation durability of two generations of 100% RAC with the effect of chloride ion corrosion. The quality evolution of recycled concrete coarse aggregate (RCA) with the increasing recycling cycles was analyzed, and carbonation depth, compressive strength and the porosity of RAC were measured before and after chloride ion corrosion. The results show that the effect of chloride ion corrosion negatively affected the carbonation resistance of RAC, and the negative effect was more severe with the increasing recycling cycles of RCA. Chloride ion corrosion led to a decrease in compressive strength, while an increase in carbonation depth and the porosity of RAC. The equation of concrete total porosity and carbonation depth was established, which could effectively judge the deterioration of carbonation resistance of RAC. [ABSTRACT FROM AUTHOR]

High-strength manufactured sand recycled aggregate concrete (MSRAC) prepared with manufactured sand (MS) and recycled coarse aggregate (RCA) is an effective way to reduce the consumption of natural aggregate resources and environmental impact of concrete industry. In this study, high-, medium- and low-quality MS, which were commercial MS local to Changzhou and 100% by volume of recycled coarse aggregate, were used to prepare MSRAC. The quality of MS was determined based on stone powder content, methylene blue value (MBV), crushing value and soundness as quality characteristic parameters. The variation laws of compressive strength and chloride penetration resistance of high-strength MSRAC with different rates of replacement and different qualities of MS were explored. The results showed that for medium- and low-quality MS, the compressive strength of the MSRAC increased first and then decreased with increasing rate of replacement. Conversely, for high-quality MS, the compressive strength gradually increased with increasing rate of replacement. The chloride diffusion coefficient of MSRAC increased with decreasing MS quality and increasing rate of replacement. The chloride diffusion coefficient of MSRAC basically met the specifications for 50-year and 100-year design working life when the chloride environmental action was D and E. To prepare high-strength MSRAC, high-quality MS can 100% replace RS (river sand), while rates of replacement of 50-75% for medium-quality MS or 25-50% for low-quality MS are proposed. Scanning Electron Microscope (SEM) images indicated that an appropriate amount of stone powder is able to improve the compressive strength of RAC, but excessive stone powder content and MBV are unfavorable to the compressive strength and chloride penetration resistance of RAC.