Effects of Hydrostatic Pressure and Cation Type on the Chloride Ion Transport Rate in Marine Concrete: An Experimental Study.

The effect of hydrostatic pressure and cation type on chloride ion transport in marine underwater concrete cannot be ignored. The study of the chloride ion transport behavior of concrete under the effect of hydrostatic pressure and cation type coupling can provide a basis for durability design and the protection of marine concrete. In this work, the chloride ion transport behavior of marine concrete in four common chloride salt solutions under different hydrostatic pressures is studied by a hydrostatic pressure test device developed by the authors. The results show that hydrostatic pressure and its action time significantly influence the chloride ion transport behavior in marine concrete; the higher the hydrostatic pressure of concrete, the faster the chloride ion transport rate. The longer the time, the more chloride ions accumulated in the same position, and the farther the chloride ion transport distance. Cation type has a certain influence on the transport process of chloride ions. Under the same test conditions, the chloride ion transport rate in a divalent cation solution is about 5% higher than that in a monovalent cation solution. The results also show that the chloride ion binding capacity under hydrostatic pressure is only 10~20% of that under natural diffusion. Using the test results, a predictive model of a chloride ion apparent transport coefficient based on the hydrostatic pressure and hydrostatic pressure action time corrected by a cation type influence coefficient is established.

Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium.

Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca2+-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins.

Preparation and Properties of Porous Concrete Based on Geopolymer of Red Mud and Yellow River Sediment.

Red mud (RM) and Yellow River sediment (YRS) are challenging to handle as waste materials. In this study, RM with geopolymer and heavy metal adsorption characteristics was combined with YRS and ground granulated blast furnace slag (GGBS) to develop a porous geopolymer with high strength and high adsorption performance. A geopolymer cementitious material with high strength was prepared using high temperature water bath curing of 90 °C and different dosages of YRS, and a porous geopolymer concrete was further prepared. The compressive strength, fluidity and setting time of geopolymer cementitious materials were tested, and the compressive strength, porosity and permeability of porous geopolymer concrete were also tested. The environmental impact assessment of geopolymer cementitious materials was further conducted. The hydration products and microstructure of geopolymer gel materials were analyzed by XRD, SEM and FT-IR tests. The results show that the addition of YRS can effectively prolong the setting time of the geopolymer cementitious material, and the enhancement rate is as high as 150% compared with the geopolymer cementitious materials without the addition of YRS. An appropriate amount of YRS can improve the compressive strength of the geopolymer cementitious materials, and its early compressive strength can be further improved under the high temperature water bath curing of 90 °C, and the compressive strength at an age of 3 d can be up to 86.7 MPa. Meanwhile, the compressive strength of porous geopolymer concrete at an age of 28 d is up to 28.1 MPa. YRS can participate in geopolymer reactions, and high temperature water bath curing can promote the reaction degree. Curing method and YRS dosages have little effect on the porosity and permeability of the porous geopolymer concrete. The porous geopolymer has a good heavy metal adsorption effect, and the alkaline pH values can be gradually diluted to neutral.

High-sensitivity detection of low-concentration heavy metal ions in solution by multiple reflection enhanced absorption (MREA) spectroscopy.

Heavy metal ions (Cr6+, Co2+, Ni2+, and Cu2+) in the electroplating and electrolysis industries are significantly related to process parameters and product quality, even at lower concentrations. Absorption spectroscopy is widely used for substance qualitative and quantitative analysis, which is an analytical method with the potential for real-time monitoring of heavy metal ions concentration in industrial processes. In this paper, a low-concentration heavy metal ion analysis method based on multiple reflection enhanced absorption (MREA) is proposed. Compared with traditional absorption, MREA has the advantages of low concentration detection limit and high-sensitivity. First, a reflective film (Al-SiO2) was prepared and a multiple reflection optical structure was designed to realize multiple parallel reflections of light in the solution medium. Then absorption spectra of low-concentration Cr6+, Co2+, Ni2+ and Cu2+ solutions were measured by MREA and traditional absorption methods. Finally, spectral bandwidth and incident light spots were optimized to obtain a superior absorption enhancement effect. The results showed that MREA could effectively increase the substance absorbance compared with traditional absorption. At the same time, with the optimal spectral bandwidth (0.4 nm) and incident light spot (1 mm), the detection limit of Cr6+, Co2+, Ni2+ and Cu2+ was reduced by 81.48%, 82.52%, 80.92% and 82.93%, respectively. The sensitivity was improved by 5-6 times, which was more obvious for low-concentration detection. In addition, the MREA method can achieve ion concentration analysis when Cr6+, Co2+, Ni2+, and Cu2+ coexist, and the linear correlative coefficients of the C-A curves were all greater than 0.999. Moreover, by adjusting reflectivity of the reflective film and the number of reflections in the optical structure, the results of the MREA method can be further optimized for the low-concentration heavy metal ion analysis. The MREA method has the advantages of simplicity, rapidity and versatility, which can provide the technical foundation for real-time monitoring method development of low-concentration heavy metal ions in industrial processes.

Direct determination of high-concentration As(III) by UV high-reference differential absorption spectroscopy for cleaner As(III) removal promotion via sulfurization.

The current methods for determining high-concentration As(III) in the high-acid matrix from the copper smelting industry are complex, time-consuming, and costly. This limits effective modulation of sulfurizing agent dosage for As(III) removal via sulfurization, aggravating hazardous waste generation. Herein, a simple, rapid, and nondestructive UV high-reference differential absorption spectroscopy was developed to directly determine high-concentration As(III) in simulated high-acid wastewater. Time-dependent density functional theory calculations indicated that the spectral curve redshift with As(III) concentration increasing was related to the decrease of electron transition energies and energy gaps. When using high-reference solutions, the least redshift in the maximum absorption wavelength and the highest upper limit of linear fitting concentration could be obtained. Therefore, the piecewise quantitative linear model of differential absorbance and concentration was established under high-reference. The quantitative range of the model within 0.06-20.00 g/L As(III) with a mean relative error of < 5.0 % and standard recovery rates within 98.0 %-104.0 % indicated high accuracy. Additionally, the relative standard deviations of < 1.5 % (n = 5) revealed good precision. All results indicated the high feasibility of the developed method in alleviating linear deviation caused by redshift and absorption saturation. Furthermore, it has potential significance in saving sulfurizing agent dosage and reducing hazardous waste generation from the source, thereby facilitating a cleaner process for removing As(III) via sulfurization.

TRPM2 as a conserved gatekeeper determines the vulnerability of DA neurons by mediating ROS sensing and calcium dyshomeostasis.

Different dopaminergic (DA) neuronal subgroups exhibit distinct vulnerability to stress, while the underlying mechanisms are elusive. Here we report that the transient receptor potential melastatin 2 (TRPM2) channel is preferentially expressed in vulnerable DA neuronal subgroups, which correlates positively with aging in Parkinson's Disease (PD) patients. Overexpression of human TRPM2 in the DA neurons of C. elegans resulted in selective death of ADE but not CEP neurons in aged worms. Mechanistically, TRPM2 activation mediates FZO-1/CED-9-dependent mitochondrial hyperfusion and mitochondrial permeability transition (MPT), leading to ADE death. In mice, TRPM2 knockout reduced vulnerable substantia nigra pars compacta (SNc) DA neuronal death induced by stress. Moreover, the TRPM2-mediated vulnerable DA neuronal death pathway is conserved from C. elegans to toxin-treated mice model and PD patient iPSC-derived DA neurons. The vulnerable SNc DA neuronal loss is the major symptom and cause of PD, and therefore the TRPM2-mediated pathway serves as a promising therapeutic target against PD.

Comparative Investigation of the Spectroscopic Behavior Based on High-Concentrated Solution in Nitrogen and Air Atmospheres.

In order to accurately obtain photometric information of high concentration SO42- and other substances in the process industry, the spectroscopy behavior of SO42-, S2-, Ni2+ and Cu2+ in air and nitrogen atmosphere was compared based on the UV-visible spectrophotometer with a nitrogen replacing the oxygen. Different from Ni2+ and Cu2+, the accuracy of SO42- and S2- in the ultraviolet region was effectively improved by using a nitrogen atmosphere (P detection results were regressed within the limited standard range, RE < 5%). The nitrogen atmosphere suppressed the additional light attenuation caused by its absorption of ultraviolet rays by isolating oxygen and was also reflected in the decrease in the degree of red shift of the characteristic wavelength for SO42- with increasing concentration. Therefore, the detection results of SO42- showed an effective improvement in sensitivity. Nevertheless, according to the complementary experimental results and theoretical calculations, in addition to oxygen absorption, the low detection accuracy of SO42- high concentration is also attributed to the reduction of the energy required for electronic excitation per unit group caused by the interaction between SO42- groups, resulting in a deviation of the C-A curve from linearity at high concentrations. The influence of this intermolecular force on the detection results is far more important than oxygen absorption. The research can provide reliable theoretical guidance and technical support for the pollution-free direct measurement of high-concentration solutions in the process industry and promote the sustainable development of the process industry.

TRPM2 protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction via modulating autophagy.

Background: Cisplatin is a widely used anti-tumor agent but its use is frequently limited by nephrotoxicity. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel which is generally viewed as a sensor of oxidative stress, and increasing evidence supports its link with autophagy, a critical process for organelle homeostasis. Methods: Cisplatin-induced cell injury and mitochondrial damage were both assessed in WT and Trpm2-knockout mice and primary cells. RNA sequencing, immunofluorescence staining, immunoblotting and flowcytometry were applied to interpret the mechanism of TRPM2 in cisplatin nephrotoxicity. Results: Knockout of TRPM2 exacerbates renal dysfunction, tubular injury and cell apoptosis in a model of acute kidney injury (AKI) induced by treatment with cisplatin. Cisplatin-caused tubular mitochondrial damage is aggravated in TRPM2-deficient mice and cells and, conversely, alleviated by treatment with Mito-TEMPO, a mitochondrial ROS scavenger. TRPM2 deficiency hinders cisplatin-induced autophagy via blockage of Ca2+ influx and subsequent up-regulation of AKT-mTOR signaling. Consistently, cisplatin-induced tubular mitochondrial damage, cell apoptosis and renal dysfunction in TRPM2-deficient mice are mitigated by treatment with a mTOR inhibitor. Conclusion: Our results suggest that the TRPM2 channel plays a protective role in cisplatin-induced AKI via modulating the Ca2+-AKT-mTOR signaling pathway and autophagy, providing novel insights into the pathogenesis of kidney injury.

DpdtpA, A Multi-metal Ion Chelator, Attenuates Tau Phosphorylation and Microglial Inflammatory Response via Regulating the PI3K/AKT/GSK-3ß Signal Pathways.

Tau protein hyperphosphorylation and formation of intracellular neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of Alzheimer's disease (AD) and positively correlated with the severity of AD symptoms. NFTs contain a large number of metal ions that play an important role in regulating tau protein phosphorylation and AD progression. Extracellular tau induces primary phagocytosis of stressed neurons and neuronal loss by activating microglia. Here, we studied the effects of a multi-metal ion chelator, DpdtpA, on tau-induced microglial activation and inflammatory responses and the underlying mechanisms. Treatment with DpdtpA attenuated the increase in the expression of NF-κB and production of inflammatory cytokines, IL-1ß, IL-6 and IL-10, in rat microglial cells induced by expression of human tau40 proteins. Treatment with DpdtpA also suppressed tau protein expression and phosphorylation. Moreover, treatment with DpdtpA prevented tau-induced activation of glycogen synthase kinase-3ß (GSK-3ß) and inhibition of phosphatidylinositol-3-hydroxy kinase (PI3K)/AKT. Collectively, these results show that DpdtpA can attenuate tau phosphorylation and inflammatory responses of microglia by regulating the PI3K/AKT/GSK-3ß signal pathways, providing a new option to alleviate neuroinflammation for the treatment of AD.

Use of Alkali-Activated Slag as an Environment-Friendly Agent for High-Performance Stabilized Soil.

Discharged slag not only occupies a large amount of land for disposal, but also causes serious environmental pollution. The use of alkali-activated slag (AAS) instead of cement as a soil-stabilization agent is beneficial for industrial waste disposal and energy conservation, which complies with the concept of green and low-carbon sustainable development in the construction industry. In this study, the compressive strength, water permeability coefficient, chloride migration coefficient and sulfate resistance of alkali-activated slag-stabilized soil (AASS) were evaluated, and compared with those of cement-stabilized soil (CSS). The hydrated crystalline phases and microscopic pore structures were analyzed by X-ray diffraction, electrochemical impedance spectroscopy (EIS) and mercury intrusion porosimetry (MIP) tests, respectively. The results indicate that, compared with CSS, AASS exhibits a higher compressive strength, lower water permeability, chloride migration coefficient and better resistance to sulfate attack, with the optimum dosage higher than 10 wt.%. The results of the MIP analysis show that the addition of AAS reduces the porosity by 6.47%. The combined use of soil and AAS proves to be a viable and sustainable method of waste utilization and carbon emission reduction in the construction industry, which provides a practical path towards carbon peaking and carbon neutrality.

TRPM2 Mediates Hepatic Ischemia-Reperfusion Injury via Ca2+-Induced Mitochondrial Lipid Peroxidation through Increasing ALOX12 Expression.

Hepatic ischemia-reperfusion (IR) injury is a serious clinical problem that complicates liver resection and transplantation. Despite recent advances in understanding of the pathophysiology of hepatic IR injury, effective interventions and therapeutics are still lacking. Here, we examined the role of transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable, non-selective cation channel, in mediating hepatic IR injury. Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction, inflammation, and cell death in mice. Moreover, RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways. Consistently, as a ferroptosis inducer, (1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this. Interestingly, TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca2+-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase (ALOX12), which results in mitochondrial lipid peroxidation during hepatic IR injury. Furthermore, hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion, both in vitro and in vivo. Collectively, these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca2+-induced ALOX12 expression, indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases, such as during liver resection and transplantation.

Electronic Excitation Characteristics and Spectral Behavior of Phosphate Anions.

Absorption spectra are fundamental bases for the qualitative and quantitative analysis of the target chemical, and the development of an analytical model can be improved by studying its characteristics and rules. In the present study, the electronic excitation characteristics of phosphate anions (H2PO4-, HPO42-, and PO43-) were analyzed based on the charge-transfer spectrum. In addition, the absorption spectra of phosphate anions at the energy level of PBE0/6-311+G (d,p) were recorded based on the time-dependent density functional theory (TD-DFT) method. Different (HPO42-)n·(H2O)10-n molecular clusters were theoretically constructed, and the combined TD-DFT method and independent gradient model revealed that red shift of the maximum absorption wavelength (λmax) with the increase of phosphate anion concentration (0-10 mM) may be caused by the decrease of hydrogen bond interaction. In addition, the prominent dispersion in the short-wave region mainly resulted in the red shift of λmax with the increase in optical path length (1-100 mm). Moreover, with the increase in spectral bandwidth (0.4-3.0 nm), λmax slightly blue-shifted because of the increase in energy through the slit, and repeatability of the corresponding absorbance measurement at λmax gradually improved. As the spectral bandwidth increased, light monochromaticity became poor, resulting in the decrease of the linearly fitted correlation coefficient of the concentration-absorbance curve. Finally, the multivariate analysis of variance results showed that the optical path length was the most significant factor that influenced the absorption spectral characteristics of phosphate anions. This study provides a basis for the qualitative and quantitative analysis of phosphate anions by using absorption spectra and also renders a theoretical reference for absorption spectroscopy of other chemicals.

TRP Channels in Oxidative Stress Signalling.

It is well established that the accumulation of high levels of reactive oxygen species (ROS), due to excessive generation of ROS and/or impaired antioxidant capacity of cells, can result in oxidative stress and cause oxidative damage to cells and their functions [...].

TRPM2 regulates cell cycle through the Ca2+-CaM-CaMKII signaling pathway to promote HCC.

BACKGROUND: HCC is one of the most common causes of cancer-related deaths. Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cation channel, was reported to be involved in carcinogenesis and tumor growth recently. However, whether TRPM2 is involved in the pathogenesis and progression of HCC remains unclear. Herein, we systematically elucidated the functional role of TRPM2 in HCC cell cycle regulation and proliferation. APPROACH AND RESULTS: We determine TRPM2 expression to be strongly upregulated in the tumor tissues of HCC patients and associated with a negative prognosis. TRPM2 is highly expressed in HCC cell lines Huh-7 and HepG2 cells, rather than in normal hepatocytes. Inhibition or silencing of TRPM2, or inhibition of the downstream Ca2+-CaM-CaMKII signaling pathway, significantly suppressed the proliferation of Huh-7 and HepG2 cells by arresting the cell cycle at the G1/S phase, accompanied with reduced expression of G1/S checkpoint proteins. Importantly, inhibition or depletion of TRPM2 remarkably slowed down the growth of patient-derived xenografts and Huh-7 xenografts in mice. CONCLUSION: Our results indicate that TRPM2 promotes HCC cell proliferation via activating the Ca2+-CaM-CaMKII signaling pathway to induce the expression of the key G1/S regulatory proteins and accelerate the cell cycle. This study provides compelling evidence of TRPM2 involvement in a previously unrecognized mechanism that drives HCC progression and demonstrates that TRPM2 is a potential target for HCC treatment.

DeepmRNALoc: A Novel Predictor of Eukaryotic mRNA Subcellular Localization Based on Deep Learning.

The subcellular localization of messenger RNA (mRNA) precisely controls where protein products are synthesized and where they function. However, obtaining an mRNA's subcellular localization through wet-lab experiments is time-consuming and expensive, and many existing mRNA subcellular localization prediction algorithms need to be improved. In this study, a deep neural network-based eukaryotic mRNA subcellular location prediction method, DeepmRNALoc, was proposed, utilizing a two-stage feature extraction strategy that featured bimodal information splitting and fusing for the first stage and a VGGNet-like CNN module for the second stage. The five-fold cross-validation accuracies of DeepmRNALoc in the cytoplasm, endoplasmic reticulum, extracellular region, mitochondria, and nucleus were 0.895, 0.594, 0.308, 0.944, and 0.865, respectively, demonstrating that it outperforms existing models and techniques.

Leveraging the ATP-P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications.

The P2X7 receptor is an exceptional member of the P2X purinergic receptor family, with its activation requiring high concentrations of extracellular adenosine 5'-triphosphate (ATP) that are often associated with tissue damage and inflammation. In the central nervous system (CNS), it is highly expressed in glial cells, particularly in microglia. In this review, we discuss the role and mechanisms of the P2X7 receptor in mediating neuroinflammation and other pathogenic events in a variety of traumatic CNS damage conditions, which lead to loss of neurological and cognitive functions. We raise the perspective on the steady progress in developing CNS-penetrant P2X7 receptor-specific antagonists that leverage the ATP-P2X7 receptor signaling axis as a potential therapeutic strategy to alleviate traumatic CNS damage and related complications.

Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage.

Stroke prognosis is negatively associated with an elevation of serum bilirubin, but how bilirubin worsens outcomes remains mysterious. We report that post-, but not pre-, stroke bilirubin levels among inpatients scale with infarct volume. In mouse models, bilirubin increases neuronal excitability and ischemic infarct, whereas ischemic insults induce the release of endogenous bilirubin, all of which are attenuated by knockout of the TRPM2 channel or its antagonist A23. Independent of canonical TRPM2 intracellular agonists, bilirubin and its metabolic derivatives gate the channel opening, whereas A23 antagonizes it by binding to the same cavity. Knocking in a loss of binding point mutation for bilirubin, TRPM2-D1066A, effectively antagonizes ischemic neurotoxicity in mice. These findings suggest a vicious cycle of stroke injury in which initial ischemic insults trigger the release of endogenous bilirubin from injured cells, which potentially acts as a volume neurotransmitter to activate TRPM2 channels, aggravating Ca2+-dependent brain injury.

The characteristics of ultraviolet absorption and electronic excitation of sulfate at high concentrations.

The variation of spectra and the characteristics of electronic excitation are critical for establishing a model for quantifying sulfate at high concentrations. The absorption characteristics of sulfate are affected by the optical pathlength and sulfate concentration. The absorption coefficient declines by approximately 86.09-96.20% with an increasing concentration (0-130 g/L) at different optical pathlengths (1-100 mm). Moreover, a high sensitivity and accuracy can be achieved at weak absorption wavelengths or at lower optical pathlengths when high concentrations of sulfate are detected. In addition, the maximum absorption wavelength of sulfate redshifts by approximately 0-10 nm with an increasing concentration and optical pathlength, which is significantly affected by the optical pathlength. The (H2SO4)n‧(H2O)4-n models were established at the PBEPBE/6-311++G(d, p) level of theory. There absorption spectra were calculated by the time-dependent density functional theory (TD-DFT) method. As a result, the maximum absorption wavelength redshifted from 180.16 nm to 192.71 nm with an increasing sulfate concentration, and the corresponding absorption coefficient demonstrated a declining trend. Furthermore, the electron-hole and natural bond orbital (NBO) analysis indicate that the type of electronic excitation changes from a n(O) â†’ σ*(S-O) localized excitation to n â†’ σ* charge-transfer excitation as the sulfate concentration increases. This study provides a theoretical foundation for understanding the spectral behavior of sulfates and constructing the quantification models or methods that can also be applied to analyze the spectroscopy of other chemicals.

Prediction of Temperature Development of Concrete with Set-Controlling Admixture Based on a New Hydration Kinetics Model.

Temperature control is needed in the construction process of massive concrete and it can avoid the concrete cracks. Prediction of temperature development based on a hydration kinetics model can reduce the need for adiabatic temperature rise tests for concrete. However, the existing hydration kinetics model cannot accurately describe the hydration process of cement, thereby limiting the ability to further accurately predict the temperature rise of concrete based on the hydration kinetics model. This paper aims to establish a new hydration kinetics model, which is based on nucleation and growth model, and to predict the temperature development of concrete with set-controlling admixture based on this model. In this paper, the nucleation and growth of hydration products and the diffusion of free water by the modified boundary of nucleation and growth (BNG) model and the modified Fuji and Kondo's model are described. The relationship between nucleation rate and apparent activation energy and the relationship between effective diffusion coefficient and apparent activation energy are linear. However, the relationship between growth rate and apparent activation is exponential. Finally, the temperature development of concrete can be calculated by the hydration degree of the cement.