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In situ temperature-dependent crystal structure of lead-free ferroelectric perovskite Ba0.798Ca0.202Zr0.006Ti0.994O3 single crystal was characterized using x-ray diffraction from 170 to 380 K. Three phases were identified at different temperatures of 170, 220, and 298 K, revealing rhombohedral (R3m), orthorhombic (Pmm2), and tetragonal (P4mm) crystal structures, respectively. The change in the bond length and its distortion are reported for both AO12 and BO6 polyhedrons, allowing for the estimation of the spontaneous polarization. The Debye–Waller factor is reported as a function of temperature for A and B-sites. Density-functional theory calculations on the tetragonal phase were performed to obtain information on the distribution of the Ca ions, the local atomic displacements, and the ideal value of the spontaneous polarization of a defect-free crystal at 0 K. We find that Ca prefers to arrange in columnar 2D plates oriented along the tetragonal axis. The Ca ions avoid being next neighbors of Zr; however, the specific arrangement of Ca has only a minor impact on the spontaneous polarization. [ABSTRACT FROM AUTHOR]

Cathode materials are usually the key to determining battery capacity, suitable cathode materials are an important prerequisite to meet the needs of large‐scale energy storage systems in the future. Polyanionic compounds have significant advantages in metal ion storage, such as high operating voltage, excellent structural stability, safety, low cost, and environmental friendliness, and can be excellent cathode options for rechargeable metal‐ion batteries. Although some polyanionic compounds have been commercialized, there are still some shortcomings in electronic conductivity, reversible specific capacity, and rate performance, which obviously limits the development of polyanionic compound cathodes in large‐scale energy storage systems. Up to now, many strategies including structural design, ion doping, surface coating, and electrolyte optimization have been explored to improve the above defects. Based on the above contents, this paper briefly reviews the research progress and optimization strategies of typical polyanionic compound cathodes in the fields of lithium‐ion batteries (LIBs) and other promising metal ion batteries (sodium ion batteries (SIBs), potassium ion batteries (PIBs), magnesium ion batteries (MIBs), calcium ion batteries (CIBs), zinc ion batteries (ZIBs), aluminum ion batteries (AIBs), etc.), aiming to provide a valuable reference for accelerating the commercial application of polyanionic compound cathodes in rechargeable battery systems. [ABSTRACT FROM AUTHOR]

Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in tumor diagnosis and therapy. However, a pyroptosis inducer based on PLNPs has not been reported yet. Herein, polyethylene glycol–poly lactic acid‐co‐glycolic acid (PEG–PLGA: PP) modified biodegradable CaS:Eu2+ (CSE@PP) PLNPs are synthesized as a pyroptosis inducer for tumor immunotherapy for the first time. The synthesized CSE@PP possesses biowindow persistent luminescence (PersL) and pH‐responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed to weak acid (pH < 6.5). During degradation within the tumor, CSE@PP constantly releases H2S and Ca2+ while its PersL gradually fades away. Thus, the PersL signal can self‐monitor H2S and Ca2+ release. Furthermore, the released H2S and Ca2+ result in mitochondrial dysfunction and the inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase‐1/GSDM‐D dependent pyroptosis and subsequent antitumor immune responses. In a word, it is confirmed that CSE@PP can self‐monitor H2S and Ca2+ release and pyroptosis‐mediated tumor Immunotherapy. This work will facilitate biomedical applications of PLNPs and inspire pyroptosis‐induced tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Calcium‐ion batteries are emerging as a promising alternative to lithium‐ion batteries by offering potential advantages in cost, affordability, and safety. However, the development of high‐performance calcium batteries has been hindered by the lack of high‐capacity cathodes. Here a small molecular organic cathode, 9,10‐phenanthrenequinone (PQ), is reported which leverages the rapid enolization chemistry of multi‐redox centers (C═O) and the flexible intermolecular structure for high performance. The PQ cathode demonstrates an impressive specific capacity of 250 mAh g−1 at 0.2 C for 200 cycles and superior rate capabilities. The robust performance of PQ cathodes is attributed to the mitigation of small molecule electrode dissolution in the weakly solvating ether electrolytes and the promotion of inter‐and intralayer Ca ion diffusion pathways, which synergistically facilitate the retention of high capacities at elevated current rates. When paired with a Ca metal anode, the full cell achieves remarkable capacities of 214 mAh g−1 at 0.2 C, with an average operating voltage of 2.5 V versus Ca/Ca2+, representing the highest performance among CMBs reported to date. The use of organic cathodes in tailored electrolytes with restricted intermediate dissolutions heralds a new era in the development of multivalent metal batteries. [ABSTRACT FROM AUTHOR]

Efficient elimination of apoptotic cells within epithelial cell sheets is crucial for preserving epithelial barrier integrity. 1 It is well established that immediate neighbors of an apoptotic cell actively participate in its removal by enclosing it within a wall of actomyosin, pushing it out in a purse-string manner in a process called apical extrusion. 2,3,4,5,6,7 Here, we found that sustained elevation of calcium ions in neighboring epithelial cells is necessary to generate the contractility required for apoptotic cell elimination. This phenomenon, which we call calcium response in effectors of apical extrusion (CaRE), highlights the disparate calcium dynamics within the epithelial sheet. Furthermore, we elucidate the essential role of desmosomes in CaRE. Specifically, we identify a subset of IP3 receptors within the endoplasmic reticulum that is recruited to the desmosome by K-Ras-induced actin-binding protein as the core component of this process. The interplay between these cellular structures heightens actomyosin contractility to drive apoptotic cell removal. Our findings underscore the physiological significance of integrating desmosomes with the endoplasmic reticulum in epithelial sheet homeostasis, shedding new light on cell-cell communication and tissue maintenance. [Display omitted] • Sustained calcium elevation (CaRE) is an effector of apical extrusion • KRAP-IP3R complex is necessary for CaRE and apoptotic cell removal • KRAP-IP3R complex localizes to desmosomes • IP3 production is upregulated at the neighbor-apoptotic cell interface Cho et al. demonstrate that sustained elevation of calcium ions in neighboring epithelial cells, which depends on the desmosome-anchored KRAP-IP3R complex, is necessary to generate the contractility required for apoptotic cell elimination. [ABSTRACT FROM AUTHOR]

Calcium-dependent protein kinases (CDPKs) serve as calcium ion sensors and play crucial roles in all aspects of plant life cycle. While CDPK gene family has been extensively studied in various plants, there is limited information available for CDPK members in oat, an important cereal crop worldwide. Totally, 60 AsCDPK genes were identified in oat genome and were classified into four subfamilies based on their phylogenetic relationship. The members within each subfamily shared similar gene structure and conserved motifs. Collinearity analysis revealed that AsCDPK gene amplification was attributed to segmental duplication events and underwent strong purifying selection. AsCDPK promoters were predicted to contain cis-acting elements associated with hormones, biotic and abiotic stresses. AsCDPK gene expressions were induced by different salt stresses, exhibiting stress-specific under different salt treatments. Moreover, overexpression of AsCDPK26 gene enhanced salt resistance in C. reinhardtii, a single-cell photoautotrophic model plants. Further analysis revealed a significant correlation between AsCDPK26 and Na+/H+ antiporter 1 (p<0.05), suggesting that AsCDPK26 may interact with ion transporter to modulate salt resistance. These results not only provide valuable insights into AsCDPK genes in response to different salt stresses, but also lay the foundation to mine novel candidates for improving salt tolerance in oat and other crops. [ABSTRACT FROM AUTHOR]

Introduction: Acupoint Catgut Embedding (ACE) is an extended and developed form of traditional acupuncture that serves as a composite stimulation therapy for various diseases. However, its local stimulation effects on acupoints remain unclear. Acupuncture can activate mechanically sensitive calcium ion channels, TRPV2 and TRPV4, located on various cell membranes, promoting Ca2+ influx in acupoint tissues to exert effects. Whether ACE can form mechanical physical stimulation to regulate these channels and the related linkage effect requires validation. Methods: This study investigates the influence of TRPV2 and TRPV4 ion channels on the local stimulation effects of ACE by embedding PGLA suture at the Zusanli (ST36) acupoint in rats and using TRPV2 and TRPV4 inhibitors. Flow cytometry, immunofluorescence, Western blot, and Real-time quantitative PCR were employed to detect intracellular Ca2+ fluorescence intensity, the expression of macrophage (Mac) CD68 and mast cell (MC) tryptase, as well as the protein and mRNA expression of TRPV2 and TRPV4 in acupoint tissues after PGLA embedding. Results: The results indicate that ACE using PGLA suture significantly increases the mRNA and protein expression of TRPV2 and TRPV4, Ca2+ fluorescence intensity, and the expression of Mac CD68 and MC tryptase in acupoint tissues, with these effects diminishing over time. The increasing trends are reduced after using inhibitors, particularly when both inhibitors are used simultaneously. Furthermore, correlation analysis shows that embedding PGLA suture at the ST36 acupoint regulates Mac and MC functions through Ca2+ signaling involving not only TRPV2 and TRPV4 but multiple pathways. Discussion: These results suggest that embedding PGLA suture at the ST36 acupoint generates mechanical physical stimulation and regulates TRPV2 and TRPV4 ion channels, which couple with Ca2+ signaling to form a linkage effect that gradually weakens over time. This provides new reference data for further studies on the stimulation effects and clinical promotion of ACE. [ABSTRACT FROM AUTHOR]

Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabetic periodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. The slow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases. Biomaterials have potential in treating periodontitis in diabetes, but addressing the range of issues with one material is challenging. Here, the authors report the development of a redox-active hydrogel for reducing inflammation and promoting tissue regeneration in diabetic periodontitis. [ABSTRACT FROM AUTHOR]

Calcium is involved in vision processes in the retina and implicated in various pathologies, including glaucoma. Rod cells rely on store-operated calcium entry (SOCE) to safeguard against the prolonged lowering of intracellular calcium ion concentrations. Zebrafish that lacked the endoplasmic reticulum Ca2+ sensor Stim2 (stim2 knockout [KO]) exhibited impaired vision and lower light perception-related gene expression. We sought to understand mechanisms that are responsible for vision impairment in stim2 KO zebrafish. The single-cell RNA (scRNA) sequencing of neuronal cells from brains of 5 days postfertilization larvae distinguished 27 cell clusters, 10 of which exhibited distinct gene expression patterns, including amacrine and γ-aminobutyric acid (GABA)ergic retinal interneurons and GABAergic optic tectum cells. Five clusters exhibited significant changes in cell proportions between stim2 KO and controls, including GABAergic diencephalon and optic tectum cells. Transmission electron microscopy of stim2 KO zebrafish revealed decreases in width of the inner plexiform layer, ganglion cells, and their dendrites numbers (a hallmark of glaucoma). GABAergic neuron densities in the inner nuclear layer, including amacrine cells, as well as photoreceptors significantly decreased in stim2 KO zebrafish. Our study suggests a novel role for Stim2 in the regulation of neuronal insulin expression and GABAergic-dependent vision causing glaucoma-like retinal pathology. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by dopaminergic neuron degeneration. Neural stem cell (NSC) therapy offers promise for replacing these neurons and restoring neural function. However, directing NSCs to become dopaminergic neurons is challenging. Retinoic acid (RA) is a potential regulator, but its insolubility in water limits its use in PD therapy. Herein, nanonizing RA with calcium acetate to create calcium‐retinoic acid nanoparticles (Ca‐RA NPs) is proposed. These nanoparticles can be internalized by NSCs and then dissociated in the acidic environment of lysosomes to lead to a burst of Ca2+ and RA. In vitro results showed that the intracellular bursting of Ca2+ and RA accelerated neuronal differentiation and maturation by 5–10 days compared to spontaneous NSC differentiation. Importantly, Ca‐RA NPs uniquely directed NSCs to dopaminergic neurons, involving the interaction between the calcium ion‐mediated MAPK signaling pathway and the RA‐mediated RA signaling pathway. Animal experiments further validated the efficacy of Ca‐RA‐coated NSCs in restoring motor and cognitive functions in PD mice by rapidly forming dopaminergic neural circuits. Given that both RA and calcium acetate are approved by the FDA, this strategy has the potential for translation into a clinical treatment approach for stem cell therapy of PD. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Cationic calcium ions can crosslink anionic alginate and pectin molecules. It was hypothesized that calcium crosslinking would improve the stability and functionality of biopolymer nanoparticles consisting of zein cores coated by alginate‐pectin shells. The effects of calcium ion addition on the structural, physicochemical, and gastrointestinal properties of quercetin‐loaded zein/alginate‐pectin nanoparticles were therefore investigated.The nanoparticles remained stable to aggregation at calcium ion concentrations of 9 mmol/L or less but aggregated and sedimented at higher concentrations. Calcium ion reinforcement increased the particle dispersion stability even at NaCl concentrations up to 1.4 molL‐1. The presence of the calcium ions also reduced quercetin release during the early stages of simulated gastrointestinal digestion but increased its release during the later stages. The relatively high release (56.1%) of quercetin from the calcium‐reinforced nanoparticles after digestion resulted in higher intracellular antioxidant activities. The pharmacokinetics of the encapsulated quercetin was measured after its oral administration to rats. The maximal concentration (Cmax) of quercetin in rat plasma for calcium‐reinforced nanoparticles was 6.1% higher than non‐reinforced nanoparticles; the half‐life (t1/2) increased by 17.5%, and the mean retention time (MRT) was 10.0% higher (P < 0.05).These results suggest that calcium ion addition improved the performance and bioavailability of nutraceutical‐loaded biopolymer nanoparticles. This might find application in the food and beverage industry. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) signaling is fundamental to cellular processes in both eukaryotic and prokaryotic organisms. While the mechanisms underlying eukaryotic Ca2+ transport are well documented, an understanding of prokaryotic transport remains nascent. LMCA1, a Ca2+ adenosine triphosphatase (ATPase) from Listeria monocytogenes, has emerged as a prototype for elucidating structure and dynamics in prokaryotic Ca2+ transport. Here, we used a multidisciplinary approach integrating kinetics, structure, and dynamics to unravel the intricacies of LMCA1 function. A cryo-electron microscopy (cryo-EM) structure of a Ca2+-bound E1 state showed ion coordination by Asp720, Asn716, and Glu292. Time-resolved x-ray solution scattering experiments identified phosphorylation as the rate-determining step. A cryo-EM E2P state structure exhibited remarkable similarities to a SERCA1a E2-P* state, which highlights the essential role of the unique P-A domain interface in enhancing dephosphorylation rates and reconciles earlier proposed mechanisms. Our study underscores the distinctiveness between eukaryotic and prokaryotic Ca2+ ATPase transport systems and positions LMCA1 as a promising drug target for developing antimicrobial strategies. [ABSTRACT FROM AUTHOR]

This document contains three research reports. The first report examines the relationship between El Niño events and rainfall patterns in the eastern Bay of Bengal. The second report focuses on resolving the Mahadayi water dispute by analyzing rainfall data and estimating water discharge in the river basin. The third report explores the use of nanoparticle-based drug delivery systems to improve the treatment of malaria. The first article discusses the dysregulation of calcium ion signaling in pancreatic acinar cells and its implications for medical conditions. The second article investigates the metabolic reprogramming in immune cells during Mycobacterium tuberculosis infection. The third article explores the use of electric fields to repel mosquitoes and prevent mosquito-borne diseases. [Extracted from the article]

Calcium sulfate whiskers (CSW) exhibit significant surface polarity and high surface energy, leading to aggregation when directly incorporated into polymer matrices, significantly affecting the mechanical properties of the composites. Sodium oleate (SO) was used to modify CSW, introducing –C=C– active groups on the surface, followed by in‐situ graft polymerization of sodium oleate‐modified CSW (SO‐CSW) with methyl methacrylate (MMA) to prepare CSW‐g‐PMMA composites. The modification mechanism of SO and PMMA on CSW, as well as the surface modification effects on CSW, were studied using DRIFT, XRD, XPS and TEM. The results show that oleic acid ions adsorb onto the surface of CSW in two forms. One is chemisorption, in which the oleic acid ions are adsorbed on the calcium ions site on the surface of CSW in a bridging way. The other is physical adsorption, oleic acid ions and dissolved calcium ions in the form of precipitation adsorbed on the outermost layer of CSW. After in‐situ polymerization, PMMA was successfully grafted onto the surface of CSW, and the thickness of the surface PMMA coating layer was approximately 67 nm. CSW‐g‐PMMA was used as a filler in the melt blending with polypropylene (PP) to prepare PP composites. CSW‐g‐PMMA mainly toughens and enhances the mechanical properties of PP composites in the form of crack bridging, crack deflection and pull‐out effect. Highlights: The mechanism of sodium oleate modified calcium sulfate whisker (CSW) has been investigated. One is chemical adsorption that the oleic acid ions are adsorbed on the calcium ions site on the CSW surface in a bridge way. The other is physical adsorption that oleic acid ions and dissolved calcium ions are adsorbed in the form of precipitation on the outer layer of CSW.After the modification of sodium oleate, the active group –C=C– was introduced on the surface of CSW, and then the PMMA long chain polymer was grafted with an in‐situ polymerization to form a PMMA coating layer with a thickness of about 67 nm, which significantly improved the hydrophobicity of CSW surface.After modification with sodium oleate and PMMA grafting, the modified CSW significantly toughened and enhanced the mechanical properties of PP composites in the form of crack bridging, crack deflection and pull‐out effect. [ABSTRACT FROM AUTHOR]

Tumor calcification is considered to have the superiority of integrating tumor diagnosis and treatment, and it also has been found to be a predictor of favorable prognosis. However, selecting suitable nanocarriers and therapeutic drugs to maximize the tumor calcification efficiency are key factors for improving calcification‐medicated theranostics. This study performs a multi‐channel calcification nanoinitiator (CalNI, i.e., BP‐Cur‐Ca@PKLAK) by loading curcumin (Cur) and depositing Ca2+ on black phosphorus (BP) and combined carrying mitochondria‐targeting cytotoxic peptide KLAK to boost a triple‐induced tumor calcification. CalNI preferentially accumulates inside tumor mitochondria and induces multilevel calcification promotion by the three combined effects of (i) the degradation of BP into PO43− provides the phosphorus source required for calcification; (ii) burst of calcium ions can directly induce cellular calcium overload; (iii) Cur can inhibit calcium efflux thus further aggravate intracellular calcium stress. Moreover, KLAK exhibited enhanced mitochondrial synergistic toxic effects. Notably, the potential function of CalNI on the regulation of macrophage polarization could completely reverse the immunosuppressive microenvironment, and activate the initiation of T cell‐mediated immune response. Therefore, this three‐pronged CalNI showed a huge promise to be an alternative to conventional oncology therapy, which presents a more satisfactory therapeutic efficiency than any kind of single induction mode. [ABSTRACT FROM AUTHOR]

The synthesis of monodisperse and stable alginate nanoparticles (ALG-NPs) was achieved through the crosslinking of sodium alginate with Ca2+ ions within sodium bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles (RMs) as nano-templates. This study addresses the challenge of controlling the size and stability of nanoparticles, which is critical for their applications in drug delivery and tissue engineering. We explored the effects of varying the water content, the choice of non-polar solvent, and the pH of the resuspension medium on nanoparticle formation. Using both n-heptane and isopropyl myristate (IPM) to form AOT RMs, we found that nanoparticle size increased with water content in both solvents, attributed to differing degrees of crosslinking efficiency influenced by the proximity of alginate and calcium ions at lower water content. Notably, IPM produced smaller and more crosslinked ALG-NPs than n-heptane, likely due to its impact on interfacial interactions. Additionally, raising the pH of the resuspension medium resulted in smaller NPs due to enhanced alginate availability for cross-linking. These findings highlight the potential of AOT RMs as versatile templates for generating polymeric nanoparticles with precise control over their characteristics. The significant role of solvent choice and pH in tailoring nanoparticle properties is underscored, providing valuable insights for future applications. The controlled size and stability of these ALG-NPs make them excellent candidates for drug delivery systems and tissue engineering, given their biocompatibility and biodegradability. [ABSTRACT FROM AUTHOR]

Mitochondria respond acutely to elevations in cytosolic Ca2+ levels, leading to increases in mitochondrial matrix Ca2+ and an increase in oxidative phosphorylation rates. Mitochondrial activity and substrate usage within skeletal muscle – the largest energy-requiring tissue – can impact total body metabolism and obesity. Mitochondrial deletion of the mitochondrial Ca2+ uniporter (MCU) complex in skeletal muscle blocks acute matrix Ca2+ uptake in genetically altered mice, which paradoxically increases fatty acid oxidation (FAO) and reduces obesity. Deletion of the MCU inhibitor gene Mcub in skeletal muscle mitochondria increases acute matrix Ca2+ uptake in genetically altered mice, which decreases FAO and promotes obesity. Skeletal muscle has a major impact on total body metabolism and obesity, and is characterized by dynamic regulation of substrate utilization. While it is accepted that acute increases in mitochondrial matrix Ca2+ increase carbohydrate usage to augment ATP production, recent studies in mice with deleted genes for components of the mitochondrial Ca2+ uniporter (MCU) complex have suggested a more complicated regulatory scenario. Indeed, mice with a deleted Mcu gene in muscle, which lack acute mitochondrial Ca2+ uptake, have greater fatty acid oxidation (FAO) and less adiposity. By contrast, mice deleted for the inhibitory Mcub gene in skeletal muscle, which have greater acute mitochondrial Ca2+ uptake, antithetically display reduced FAO and progressive obesity. In this review we discuss the emerging concept that dynamic fluxing of mitochondrial matrix Ca2+ regulates metabolism. [ABSTRACT FROM AUTHOR]

Simple Summary: Lead (Pb) and mercury (Hg) are two of the major heavy metals of antiquity and have gained considerable importance as potent pollutants in aquatic environments. It is known that fish embryos or larvae are more sensitive to the monitoring of heavy metal contamination. Thus, RNA sequencing (RNA-seq) analysis based on physiological changes in larval zebrafish was conducted to investigate the toxic mechanisms of lead or mercury in fish during early life stages. Our results showed that acute lead exposure significantly decreased survival but increased the malformation rates of developing zebrafish from 48 hpf to 120 hpf. Transcriptomic analysis revealed that lead-triggered biological processes included cellular process, metabolic process, biological regulation, and response to stimulus. The most enriched lead-regulated pathways included cytochrome P450, glutathione metabolism, and lipid metabolism. Moreover, a series of differentially expressed genes (DEGs) were identified by both mercury and lead treatment, which could be useful for searching potential molecular markers against the evaluation of heavy metals contamination. This study was first conducted to investigate the effects of acute lead exposure on developing zebrafish embryos or larvae from 24 to 120 h post-fertilization (hpf). Our data showed that treatment with 50–200 μM lead significantly affected larval survivability and morphology compared to the respective control. Second, we chose 120 hpf larvae treated with 12.5 μM lead for RNA sequencing due to its exposure level being sufficient to produce toxic effects with minimum death and lead bioaccumulation in developing zebrafish. A total of 137.45 million raw reads were obtained, and more than 86% of clean data were mapped to the zebrafish reference genome. Differential expression profiles generated 116 up- and 34 down-regulated genes upon lead exposure. The most enriched GO terms for representative DEGs were ion transport and lipid metabolism. Third, a comparison with the dataset of mercury-regulated gene expression identified 94 genes (64 up-regulated and 30 down-regulated) for exposure specific to lead, as well as 422 genes (338 up-regulated and 84 down-regulated) for exposure specific to mercury. In addition, 56 genes were co-regulated by micromolar mercury and lead treatment, and the expression of thirteen genes, including mt2, ctssb.1, prdx1, txn, sqrdl, tmprss13a, socs3a, trpv6, abcb6a, gsr, hbz, fads2, and zgc:92590 were validated by qRT-PCR. These genes were mainly associated with metal ion binding, proteolysis, antioxidant activity, signal transduction, calcium ion or oxygen transport, the fatty acid biosynthetic process, and protein metabolism. Taken together, these findings help better understand the genome-wide responses of developing zebrafish to lead or mercury and provide potential biomarkers for acute exposure to toxic metals. [ABSTRACT FROM AUTHOR]

In tropical islands, calcareous sand with poor engineering properties usually needs to be treated before it can be used as building materials. Considering the scarcity of freshwater in these areas, this study proposes seawater-based enzyme induced carbonate precipitation (EICP) technology to enhance the properties of calcareous sand. It is to induce calcium carbonate crystals to bond calcareous sand particles together using the seawater-based crude soybean enzyme and cementation solution (i.e., urea and calcium chloride). In this study, the crude soybean urease extraction test was firstly carried out using seawater and it was also investigated what components of seawater had a greater effect on the soybean urease extraction. Afterwards, the solution test was conducted to explore the ability of the extracted urease in inducing calcium carbonate through analyzing the variation of concentration of calcium ions and pH of the solution. Finally, the biocementation effect of EICP treated calcareous sand using the seawater extracted urease solution was evaluated by the unconfined compressive strength (quc) and microscopic analysis. Test results show that the turbidity of the seawater-extracted soybean urease solution can be reduced by 66.7% compared to that of deionised water extracted urease, with only a slight reduction in urease activity. Among all the components of seawater, NaCl, MgCl2, CaCl2, NaHCO3 and KBr can significantly reduce the turbidity of soybean urease solution. The lower turbidity can effectively avoid bioclogging and contribute to the homogeneity of the EICP-treated calcareous sands, and thus improve the biomineralization efficiency and strength enhancement. Seawater-based EICP treatment will be a great promising technology in freshwater-scarce tropical islands, because it can directly use seawater for biomineralization treatment of calcareous sand, and meanwhile effectively avoid local clogging of biocementation. [ABSTRACT FROM AUTHOR]

Dispersive soil is a widely distributed problematic soil in arid or semiarid areas of the world and can cause pipe erosion, gully damage and other seepage failures. This study analyzed the effect of environmentally friendly enzyme-induced carbonate precipitation (EICP) on the dispersivity of dispersive soils. This methodology was tested for the stabilization of three dispersive soil types (two high-sodium soils, two low-clay-content soils, and two soils with both high sodium and low clay contents) to examine the impact on dispersivity based on the results of pinhole tests and mud ball tests. Physical, chemical, mechanical, and microscopic tests were also conducted to investigate the effects of the components in the EICP reaction solution on dispersive soil modification. The experiments showed that the concentration of the reaction solution and the curing time required to limit the dispersivity decreased with increasing clay content in the soil. Ca2+ limited the dispersivities of dispersive soils via four distinct mechanisms. The first mechanism was ion exchange; Ca2+ decreased the percentage of exchangeable sodium ions to less than 7% while reducing the thickness of the diffuse double layer such that the spacings between soil particles were reduced and the chemical dispersivity was limited. Second, Ca2+ increased the viscosity of the solution by salting out the organic matter present in the soybean urease. Subsequently, the D1-class physically dispersive soil was converted into an ND2-class nondispersive soil. Third, Ca2+ decreased the soil pH by reducing the CO32− content, which could hydrolyze to increase the soil alkalinity. Finally, the presence of Ca2+ led to the generation of cementitious minerals through the precipitation of CaCO3 crystals that continuously generated CO32−, filling and cementing soil particles and thereby limiting their physical dispersivity. These results indicated that a low-concentration EICP reaction solution efficiently controlled the dispersivities of the three dispersive soils. [ABSTRACT FROM AUTHOR]

Even though there have been significant advancements in the development of Cr3+‐activated near‐infrared (NIR) phosphors, the challenge still remains to develop highly efficient and thermally stable NIR phosphors. Here, the Ca4‐xZnxHfGe3O12:0.03Cr3+ solid solution phosphors with 834–806 nm NIR emission are constructed by substituting Zn2+ for Ca2+, thereby facilitating the formation of [ZnO6] luminescence site. The coexistence of [HfO6] and [Zn/CaO6] luminescence centers is confirmed through DFT calculation, time‐resolved photoluminescence (TRPL) spectroscopy, and low‐temperature‐photoluminescence (77 K) spectroscopy. The formation of [ZnO6] effectively resolves the issue of lattice mismatch between Cr3+ and Ca2+. Furthermore, the simultaneous enhancement of luminescence intensity and thermal stability is realized through a synergistic combination of lattice distortion and rigidity enhancement. By optimizing the substitution concentration of Cr3+, the internal quantum efficiency (IQE) of 92% and an external quantum efficiency (EQE) of 29% are finally achieved. Meanwhile, the thermal stability is also enhanced from 59%@400 K (x = 0) to 81%@400 K (x = 0.8). The developed NIR phosphor‐converted light‐emitting diodes (pc‐LEDs) exhibit promising prospects in the fields of security, biomedicine, non‐destructive testing and rapid identification. [ABSTRACT FROM AUTHOR]

Purpose: Chordomas are malignant tumors that destroy bones, compress surrounding nerve tissues and exhibit phenotypes that recapitulate notochordal differentiation in the axial skeleton. Chordomas recur frequently, as they resist radio-chemotherapy and are difficult to completely resect, leading to repeated bone destruction and local expansion via unknown mechanisms. Here, using chordoma specimens and JHC7 chordoma cells, we asked whether chordoma cells possess bone-dissolving activity. Methods: CT imaging and histological analysis were performed to evaluate the structure and mineral density of chordoma-invaded bone and osteolytic marker expression. JHC7 cells were subjected to immunocytochemistry, imaging of cell fusion, calcium dynamics and acidic vacuoles, and bone lysis assays. Results: In patients, we found that the skull base invaded by chordoma was highly porous, showed low mineral density and contained brachyury-positive chordoma cells and conventional osteoclasts both expressing the osteolytic markers tartrate-resistant acid phosphatase (TRAP) and collagenases. JHC7 cells expressed TRAP and cathepsin K, became multinucleated via cell-cell fusion, showed spontaneous calcium oscillation, and were partly responsive to the osteoclastogenic cytokine RANKL. JHC7 cells exhibited large acidic vacuoles, and nonregulatory bone degradation without forming actin rings. Finally, bone-derived factors, calcium ions, TGF-β1, and IGF-1 enhanced JHC7 cell proliferation. Conclusion: In chordoma, we propose that in addition to conventional bone resorption by osteoclasts, chordoma cells possess bone-dissolving activity at the tumor-bone boundary. Furthermore, bone destruction and tumor expansion may occur in a positive feedback loop. [ABSTRACT FROM AUTHOR]

The regulation of insulin in pancreatic β$\beta$‐cells is dependent on changes in the cytoplasmic calcium concentration ([Ca2+]i)$({[{Ca}^{2+}]}_i)$. The well‐balanced influx and efflux routes are required for insulin secretion. Therefore, this research presents a simplified yet valuable model for investigating calcium dynamics in a β$\beta$‐cell under 2D unsteady state conditions. The model integrates diffusion, reactions involving sources, excess buffers, and fluxes, including efflux through leak and SERCA mechanisms. Boundary and initial conditions are tailored to β$\beta$‐cell physiology. Numerical solutions are computed using the finite element method with co‐axial circular elements, chosen for their effectiveness in discretizing the cell domain and improving accuracy. This approach minimizes errors, enhancing predictive fidelity and capturing the intricate geometries and dynamics within β$\beta$‐cells. The model's findings highlight the influence of buffers and source influx on calcium regulation, and integrate temporal fluctuations in IP3(Inositol 1,4,5‐Trisphosphate) synthesis and degradation, Adenosine Triphosphate (ATP) generation, insulin release, and metabolic processes. Computational analysis suggests disruptions in cellular energy production and metabolite distribution may underlie conditions like metabolic syndrome and diabetes. This study contributes to a deeper understanding of β$\beta$‐cell biology, potentially informing therapeutic strategies for related disorders. [ABSTRACT FROM AUTHOR]

Mammalian olfactory sensory neurons (OSNs) generate an odorant‐induced response by sequentially activating two ion channels, which are in their ciliary membranes. First, a cationic, Ca2+‐permeable cyclic nucleotide‐gated channel is opened following odorant stimulation via a G protein‐coupled transduction cascade and an ensuing rise in cAMP. Second, the increase in ciliary Ca2+ opens the excitatory Ca2+‐activated Cl− channel TMEM16B, which carries most of the odorant‐induced receptor current. While the role of TMEM16B in amplifying the response has been well established, it is less understood how this secondary ion channel contributes to response kinetics and action potential generation during single as well as repeated stimulation and, on the other hand, which response properties the cyclic nucleotide‐gated (CNG) channel determines. We first demonstrate that basic membrane properties such as input resistance, resting potential and voltage‐gated currents remained unchanged in OSNs that lack TMEM16B. The CNG channel predominantly determines the response delay and adaptation during odorant exposure, while the absence of the Cl− channels shortens both the time the response requires to reach its maximum and the time to terminate after odorant stimulation. This faster response termination in Tmem16b knockout OSNs allows them, somewhat counterintuitively despite the large reduction in receptor current, to fire action potentials more reliably when stimulated repeatedly in rapid succession, a phenomenon that occurs both in isolated OSNs and in OSNs within epithelial slices. Thus, while the two olfactory ion channels act in concert to generate the overall response, each one controls specific aspects of the odorant‐induced response. Key points: Mammalian olfactory sensory neurons (OSNs) generate odorant‐induced responses by activating two ion channels sequentially in their ciliary membranes: a Na+, Ca2⁺‐permeable cyclic nucleotide‐gated (CNG) channel and the Ca2⁺‐activated Cl⁻ channel TMEM16B.The CNG channel controls response delay and adaptation during odorant exposure, while TMEM16B amplifies the response and influences the time required for the response to reach its peak and terminate.OSNs lacking TMEM16B display faster response termination, allowing them to fire action potentials more reliably during rapid repeated stimulation.The CNG and TMEM16B channels have distinct and complementary roles in shaping the kinetics and reliability of odorant‐induced responses in OSNs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Citrus products often suffer from delayed bitterness, which is generated from the conversion of non‐bitter precursors (limonoate A‐ring lactone, LARL) to limonin under the catalysis of limonin D‐ring lactone hydrolase (LDLH). In this study, LDLH was isolated and purified from sweet orange seeds, and a rapid and accurate high‐performance liquid chromatography method to quantify LARL was developed and applied to analyze the activity and enzymatic properties of purified LDLH. RESULTS: Purified LDLH (25.22 U mg−1) showed bands of 245 kDa and 17.5 kDa molecular weights in native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate PAGE analysis respectively. After a 24 h incubation under strongly acidic (pH 3) or strongly alkaline (pH 9) conditions, LDLH still retained approximately 100% activity. Moreover, LDLH activity was not impaired by thermal treatment at 50 °C for 120 min. Enzyme inhibition assays showed that LDLH was inactivated only after ethylenediaminetetraacetic acid treatment, and other enzyme inhibitors showed no significant effect on its activity. In addition, the LDLH activity of calcium ion (Ca2+) intervention was 108% of that in the blank group, and that of zinc ion (Zn2+) intervention was 71%. CONCLUSION: LDLH purified in this study was a multimer containing 17.5 kDa monomer with a wide pH tolerance range (pH 3–9) and excellent thermal stability. Moreover, LDLH might be a metallopeptidase, and its activity was stimulated by Ca2+ and significantly inhibited by Zn2+. These findings improve our understanding of LDLH and provide some important implications for reducing the bitterness in citrus products in the future. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The manipulation of cytosolic Ca2+ concentration ([Ca2+]i) plays a crucial role in the study of Ca2+ signaling and the therapy of its affected diseases. Nanotechnology enables the development of nanotransducers for targeted, non‐invasive, highly spatiotemporal, and on‐demand [Ca2+]i regulation by responding to external energy fields to activate Ca2+ channels, in situ deliver Ca2+, or release the payload of chemical modulators. As considerable strides have been made in Ca2+ signaling‐related fundamental research and applications in recent years, in this article, it is tried to present a thorough review of nanotransducer‐based [Ca2+]i manipulation, from the working principle to specific applications. Focusing on the design rationale and constructions of nanotransducers, the interactions between nanotransducers and Ca2+ channels are highlighted, as well as the downstream effectors of Ca2+ signaling pathways, followed by their representative biomedical applications in disease treatment and neuromodulation. Moreover, despite the enormous progress made to date, nanotransducer‐regulated Ca2+ signaling still confronts obstacles, and several scientific issues urgently need to be resolved. Thus, to provide brief and valid instructions for the development of nanotransducers for the regulation of Ca2+ signaling, proposals on how to improve the nanotransducer‐based [Ca2+]i manipulation as well as future challenges and prospects are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Ascending aortic aneurysm is a serious health risk. In order to study ascending aortic aneurysms, elastase and calcium ion treatment for aneurysm formation are mainly used, but their aneurysm formation time is long and the aneurysm formation rate is low. Thus, this study aimed to construct a rat model of ascending aorta aneurysm with a short modeling time and high aneurysm formation rate, which may mimic the pathological processes of human ascending aorta aneurysm. Methods: Cushion needles with different pipe diameters (1.0, 1.2, 1.4, and 1.6 mm) were used to establish a human-like rat model of ascending aortic aneurysm by narrowing the ascending aorta of rats and increasing the force of blood flow on the vessel wall. The vascular diameters were evaluated using color Doppler ultrasonography after 2 weeks. The characteristics of ascending aortic aneurysm in rats were detected by Masson's trichrome staining, Verhoeff's Van Gieson staining, and hematoxylin and eosin staining, while real-time polymerase chain reaction was utilized to assess the total RNA of cytokine interleukin-1β, interleukin 6, transforming growth factor-beta 1, and metalloproteinase 2. Results: Two weeks after surgery, the ultrasound images and the statistical analysis demonstrated that the diameter of the ascending aorta in rats increased more than 1.5 times, similar to that in humans, indicating the success of animal modeling of ascending aortic aneurysm. Moreover, the optimal constriction diameter of the ascending aortic aneurysm model is 1.4 mm by the statistical analysis of the rate of ascending aortic aneurysm and mortality rate in rats with different constriction diameters. Conclusions: The human-like ascending aortic aneurysm model developed in this study can be used for the studies of the pathological processes and mechanisms of ascending aortic aneurysm in a more clinically relevant fashion. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum stress triggers the unfolded protein response (UPR) to promote cell survival or apoptosis. Transient endoplasmic reticulum stress activation has been reported to trigger megakaryocyte production, and UPR activation has been reported as a feature of megakaryocytic cancers. However, the role of UPR signaling in megakaryocyte biology is not fully understood. We studied the involvement of UPR in human megakaryocytic differentiation using PMA (phorbol 12‐myristate 13‐acetate)‐induced maturation of megakaryoblastic cell lines and thrombopoietin‐induced differentiation of human peripheral blood‐derived progenitors. Our results demonstrate that an adaptive UPR is a feature of megakaryocytic differentiation and that this response is not associated with ER stress‐induced apoptosis. Differentiation did not alter the response to the canonical endoplasmic reticulum stressors DTT or thapsigargin. However, thapsigargin, but not DTT, inhibited differentiation, consistent with the involvement of Ca2+ signaling in megakaryocyte differentiation. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the effect of non‐selenium glutathione peroxidase (NSGPx) activity of Peroxiredoxin 6 (Prdx6) on beef tenderness. Longissimus thoracis et lumborum (LTL) muscle from six cattle were obtained at 30 min post‐mortem. Samples from each muscle were randomly assigned to each of four treatment groups: being incubated in H2O2 (simulation of oxidative stress), mercaptosuccinic acid (MA; inhibiting NSGPx activity), N‐acetyl‐L‐cysteine (NAC; inhibiting oxidative stress and increasing NSGPx activity), and saline (control), respectively. Results indicated that cells increased the expression of Prdx6 and NSGPx activity to resist oxidative stress. The inhibition of NSGPx activity group (MA) significantly decreased the Warner‐Bratzler shear force and increased the degradation of desmin. Moreover, both the H2O2 and the MA treatment significantly increased the Ca2+ concentration in the sarcoplasm, cell apoptotic rate, and caspase 9 and 3 activity. These results demonstrated that inhibiting NSGPx activity of Prdx6 could accelerate beef tenderization by promoting mitochondrial apoptosis. [ABSTRACT FROM AUTHOR]

High‐intensity interval training (HIIT) has shown significant results in addressing adiposity and risk factors associated with obesity. However, there are no studies that investigate the effects of HIIT on contractility and intracellular Ca2+ handling. The purpose of this study was to explore the impact of HIIT on cardiomyocyte contractile function and intracellular Ca2+ handling in rats in which obesity was induced by a saturated high‐fat diet (HFD). Male Wistar rats were initially randomized into a standard diet and a HFD group. The experimental protocol spanned 23 weeks, comprising the induction and maintenance of obesity (15 weeks) followed by HIIT treatment (8 weeks). Performance was assessed using the maximum oxygen consumption test (V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$). Evaluation encompassed cardiac, adipose and skeletal muscle histology, as well as contractility and intracellular Ca2+ handling. HIIT resulted in a reduction in visceral area, an increase in V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$, and an augmentation of gastrocnemius fibre diameter in obese subjects. Additionally, HIIT led to a decrease in collagen fraction, an increase in percentage shortening, and a reduction in systolic Ca2+/percentage shortening and systolic Ca2+/maximum shortening rates. HIIT induces physiological cardiac remodelling, enhancing the contractile function of cardiomyocytes and improving myofilament sensitivity to Ca2+ in the context of obesity. This approach not only enhances cardiorespiratory and physical performance but also reduces visceral area and prevents interstitial fibrosis. What is the central question of this study?Does high‐intensity interval training (HIIT) enhance myocardial contractility in models of obesity induced by a saturated high‐fat diet, and does it promote an improvement in intracellular Ca2+ handling (Ca2+ influx and reuptake)?What is the main finding and its importance?HIIT, as a non‐pharmacological tool of short duration but high intensity, improves cardiovascular function and the sensitivity of myofilaments to intracellular Ca2+ handling, as well as promoting a reduction in visceral fat area. Thus, the obesity‐induced impairment of the heart's contractile properties was partially prevented by an 8‐week HIIT programme. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAp) is a versatile material with wide-ranging applications, including its utility as an adsorbent. However, its brittleness and limited adsorption capacity pose challenges, prompting the incorporation of chi)tosan (CTS) fillers to enhance mechanical strength and adsorption properties. The hydroxyapatite/chitosan (HAp/CTS) composite was synthesized via the in-situ method, utilizing natural sources such as calcium ions from cuttlefish bones and chitosan extracted from shrimp shells. Various chitosan concentrations (10, 20, 30, 40, and 50 wt%) were explored in the synthesis process, with the optimal adsorption of Rhodamine B dye observed at a 30% concentration, yielding 0.1832 mg/g. Validation of the HAp/CTS composite synthesis was achieved through X-ray diffraction, revealing the presence of CTS at a new peak at 2θ of 19.23°, while infrared spectroscopy confirmed absorption bands for both HAp and CTS. Additionally, scanning electron microscopy-energy dipersive spectroscopy (SEM-EDS) investigations revealed irregular shapes with agglomeration, resulting in a Ca/P ratio of 1.80 for the HAp/CTS composite. The HAp/CTS-30% composite demonstrated efficient Rhodamine B dye adsorption following the Freundlich isotherm equation, pseudo-second-order adsorption kinetics, and exhibited good reusability. These findings suggest that the HAp/CTS composite could serve as a promising, cost-effective solution for treating industrial wastewater. [ABSTRACT FROM AUTHOR]

Imidacloprid and other neonicotinoid insecticides severely impact the performance and survival of honey bees and other pollinators. In the present study, we focused on the gene expression profile of newly emerged Apis mellifera queen bees after sublethal imidacloprid treatment during the larval stage. Royal jelly containing 1 ppb imidacloprid was provided to larvae for 3 consecutive days (2–4 days postemergence). Queen larvae treated with imidacloprid showed lower capping and emergence rates (35.5% and 24.22%, respectively) than did control larvae (61.68% and 52.95%, respectively), indicating a high failure rate of queen rearing associated with imidacloprid exposure during the larval stage. The molecular response to imidacloprid treatment was examined next. By comparing the gene expression profiles of imidacloprid‐treated queen larvae and those of control queen larvae using DESeq2, we identified 215 differentially expressed genes, with 105 and 111 up‐ and downregulated genes, respectively. Gene Ontology results indicated that chitin binding– and calcium ion binding–related genes were upregulated, while phototransduction‐ and visual perception–related genes were downregulated. The high mortality rate and altered gene expression profiles suggest that treatment with even 1 ppb imidacloprid can severely impact queen bee survival. Environ Toxicol Chem 2024;43:2232–2242. © 2024 SETAC [ABSTRACT FROM AUTHOR]

• S-NZVI/rGO@GG slurry showed excellent stability and mobility performance. • Higher GG concentration, pH, and low ionic strength are beneficial to improve the transportability of S-NZVI/rGO@GG slurry. • Brownian action dominates S-NZVI/rGO@GG slurry deposition in saturated porous media. • CFT, XDLVO, and kinetic fitting were combined to explain attenuated Brownian motion and GG spatial repulsion play a key role in migration. Nanoscale zero-valent iron (NZVI), which has the advantages of small particle size, large specific surface area, and high reactivity, is often injected into contaminated aquifers in the form of slurry. However, the prone to passivation and agglomeration as well as poor stability and mobility of NZVI limit the further application of this technology in fields. Therefore, sulfided NZVI loaded on reduced graphene oxide (S-NZVI/rGO) and guar gum (GG) with shear-thinning properties as stabilizers were used to synthesize S-NZVI/rGO@GG slurries. SEM, TEM, and FT-IR confirmed that the dispersion and anti-passivation of NZVI were optimized in the coupled system. The stability and mobility of the slurry were improved by increasing the GG concentration, enhancing the pH, and decreasing the ionic strength and the presence of Ca2+ ions, respectively. A modified advection-dispersion equation (ADE) was used to simulate the transport experiments considering the strain and physicochemical deposition/release. Meanwhile, colloidal filtration theory (CFT) demonstrated that Brownian motion plays a dominant role in the migration of S-NZVI/rGO@GG slurry, and the maximum migration distance can be increased by appropriately increasing the injection rate. Extended-Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory showed that the excellent stability and migration of S-NZVI/rGO@GG slurry mainly came from the GG spatial forces. This study has important implications for the field injection of S-NZVI/rGO@GG slurry. According to the injection parameters, the injection range of S-NZVI/rGO@GG slurry is effectively controlled, which lays the foundation for the promotion of application in actual fields. [Display omitted] [ABSTRACT FROM AUTHOR]

The purpose of this study is to explore the shared molecular pathogenesis of traumatic brain injury (TBI) and high-grade glioma and investigate the mechanism of propofol (PF) as a potential protective agent. By analyzing the Chinese glioma genome atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, we compared the transcriptomic data of high-grade glioma and TBI patients to identify common pathological mechanisms. Through bioinformatics analysis, in vitro experiments and in vivo TBI model, we investigated the regulatory effect of PF on extracellular matrix (ECM)-related genes through Prrx1 under oxidative stress. The impact of PF on BBB integrity under oxidative stress was investigated using a dual-layer BBB model, and we explored the protective effect of PF on tight junction proteins and ECM-related genes in mice after TBI. The study found that high-grade glioma and TBI share ECM instability as an important molecular pathological mechanism. PF stabilizes the ECM and protects the BBB by directly binding to Prrx1 or indirectly regulating Prrx1 through miRNAs. In addition, PF reduces intracellular calcium ions and ROS levels under oxidative stress, thereby preserving BBB integrity. In a TBI mouse model, PF protected BBB integrity through up-regulated tight junction proteins and stabilized the expression of ECM-related genes. Our study reveals the shared molecular pathogenesis between TBI and glioblastoma and demonstrate the potential of PF as a protective agent of BBB. This provides new targets and approaches for the development of novel neurotrauma therapeutic drugs. [ABSTRACT FROM AUTHOR]

In general, municipal solid waste incinerator bottom ash (IBA) is mainly utilized as fillers in nonstructural concrete products due to its low reactivity. In this study, the high-strength alkali-activated materials (AAMs) using high calcium IBA was developed. A ternary contour diagram was introduced to optimize the composition of thermally activated IBA (TMBA), ground granulated blast furnace slag (GGBS), and fly ash (FA) in AAMs. The result showed that a high concentration of calcium ions in the ternary system contributed to the provision of nucleation sites for the precipitation of products, thus leading to the promotion of hardening. The optimal compressive strength (80–85 MPa) of AAMs was achieved using 60%–80% GGBS content, 10%–40% TMBA content, and 0%–10% FA content. The AAMs showed high resistance to sulphate attack, chloride penetration, and freeze-thaw when the TMBA content was less than 40%. This was attributed to a dense pore structure formation promoted by the presence of calcium minerals (anorthite, wollastonite, mayenite and gehlenite) as indicated in the X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM) analysis. The embodied CO2 index of the AAMs was about 59%–87% lower than cement, and it was a cleaner cementitious material. [ABSTRACT FROM AUTHOR]

The current study tested the hypothesis that an increase in the ionic levels (Na+, Cl--, Ca2+, Mg2+, and K+) in the gastrointestinal tract (GIT), and hepatosomatic index (HSI), gonadosomatic index (GSI), and Fulton's condition factor (FCF) are associated with the reproduction period of silver catfish (Rhamdia quelen). So, we verified ionic levels of the fluid phase of the different portions of the GIT content, HSI, GSI, and FCF of silver catfish in different seasons in a dam in southern Brazil. The highest Na+ and Cl-- levels in GIT were found in spring. The stomach's Na+ and Cl-- values were lower than the other segments. The K+ and Ca2+ levels in GIT were higher in winter, except in the stomach, where the values increased in summer. The highest K+ levels were reported in the anterior intestine. The highest Ca2+ levels in winter and spring were reported in the anterior and mid-intestines. In summer, the Mg2+ levels in the intestine were lower. The values of GSI and FCF were higher in winter and spring, and those of HSI were higher in winter. In conclusion, ions in the GIT and HSI, GSI, and FCF were higher in the reproduction period (winter for spring). [ABSTRACT FROM AUTHOR]

Well-Root PT is a novel bioceramic material developed to overcome limitations of conventional calcium silicate cements. The purpose of this study was to assess the biocompatibility and bioactivity of a premixed putty-type cement, Well-Root PT. Identical cylindrical samples were prepared from ProRoot MTA, Biodentine, and Well-Root PT. In vitro calcium weight volume and calcium ion release from the materials were evaluated with scanning electron microscopy and energy-dispersive spectroscopy and inductively coupled plasma-optical emission spectroscopy. An in vivo rat direct pulp capping model was implemented with the materials (n = 14 per material). The rats were sacrificed at 7 or 28 days. Hematoxylin and eosin and immunohistochemical analyses were performed. In vitro calcium weight volume was 42.83 ± 8.82 % in ProRoot MTA, 47.05 ± 8.83 % in Biodentine, and 29.99 ± 4.94 % in Well-Root PT. Calcium ion releases from Well-Root PT after 7 and 28 days were similar with those from ProRoot MTA, but lower than those from Biodentine (P = 0.001 after 7 and 28 days equally). In an in vivo rat model, hematoxylin and eosin analysis showed no significant differences in inflammatory infiltration (P = 0.393) and hard tissue formation scores among the materials (P = 0.905). Also, both CD68 and DSPP expression showed similar results, with no significant differences among the materials (equally P = 0.874 for both markers). Within the limits of this study, Well-Root PT was comparable to ProRoot MTA and Biodentine in terms of biocompatibility and bioactivity. [ABSTRACT FROM AUTHOR]

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Oocyte activation failure is thought to be one of the main factors for total fertilisation failure (TFF) after intracytoplasmic sperm injection (ICSI), which could be induced by abnormal calcium oscillations. Phospholipase C zeta (PLCZ), a sperm factor, is associated with Ca2+ oscillations in mammalian oocytes. To date, some mutations in PLCZ1 (the gene that encodes PLCZ) have been linked to TFF, as demonstrated by the observed reduction in protein levels or activity to induce Ca2+ oscillations. In this study, normozoospermic males whose sperms exhibited TFF after ICSI and their families were recruited. First, mutations in the PLCZ1 sequence were identified by whole exome sequencing and validated using Sanger sequencing. Then, the locations of PLCZ1/PLCZ and the transcript and protein levels in the sperm of the patients were studied. Subsequently, in vitro function analysis and in silico analysis were performed to investigate the function-structure correlation of mutations identified in PLCZ1 using western blotting, immunofluorescence, RT-qPCR, and molecular simulation. Ca2+ oscillations were detected after cRNA microinjection into MII mouse oocytes to investigate calcium oscillations induced by abnormal PLCZ. Five variants with compound heterozygosity were identified, consisting of five new mutations and three previously reported mutations distributed across the main domains of PLCZ, except the EF hands domain. The transcript and protein levels decreased to varying degrees among all detected mutations in PLCZ1 when transfected in HEK293T cells. Among these, mutations in M138V and R391* of PLCZ were unable to trigger typical Ca2+ oscillations. In case 5, aberrant localisation of PLCZ in the sperm head and an increased expression of PLCZ in the sperm were observed. In conclusion, this study enhances the potential for genetic diagnosis of TFF in clinics and elucidates the possible relationship between the function and structure of PLCZ in novel mutations. [ABSTRACT FROM AUTHOR]

Itch is a protective sensation that drives scratching. Although specific cell types have been proposed to underlie itch, the neural basis for itch remains unclear. Here, we used two-photon Ca2+ imaging of the dorsal horn to visualize neuronal populations that are activated by itch-inducing agents. We identify a convergent population of spinal interneurons recruited by diverse itch-causing stimuli that represents a subset of neurons that express the gastrin-releasing peptide receptor (GRPR). Moreover, we find that itch is conveyed to the brain via GRPR-expressing spinal output neurons that target the lateral parabrachial nuclei. We then show that the kappa opioid receptor agonist nalfurafine relieves itch by selectively inhibiting GRPR spinoparabrachial neurons. These experiments provide a population-level view of the spinal neurons that respond to pruritic stimuli, pinpoint the output neurons that convey itch to the brain, and identify the cellular target of kappa opioid receptor agonists for the inhibition of itch. [ABSTRACT FROM AUTHOR]

Cyclometalated iridium(III) compounds have been widely explored due to their outstanding photo-physical properties and multiple anticancer activities. In this paper, three cyclometalated iridium(III) compounds [Ir(ppy)2(DBDIP)]PF6 (5a), [Ir(bzq)2(DBDIP)]PF6 (5b), and [Ir(piq)2(DBDIP)]PF6 (5c) (ppy: 2-phenylpyridine; bzq: benzo[h]quinoline; piq: 1-phenylisoquinoline, and DBDIP: 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and the mechanism of antitumor activity was investigated. Compounds photoactivated by visible light show strong cytotoxicity against tumor cells, especially toward A549 cells. Biological experiments such as migration, cellular localization, mitochondrial membrane potential and permeability, reactive oxygen species (ROS) and calcium ion level detection were performed, and they demonstrated that the compounds induced the apoptosis of A549 cells through a mitochondrial pathway. At the same time, oxidative stress caused by ROS production increases the release of damage-related molecules and the expression of porogen gasdermin D (GSDMD), and the content of LDH released from damaged cell membranes also increased. Besides, the content of the lipid peroxidation product, malondialdehyde (MDA), increased and the expression of GPX4 decreased. These indicate that the compounds promote cell death by combining ferroptosis and pyroptosis. The results reveal that cyclometalated iridium(III) compounds 5a–5c may be a potential chemotherapeutic agent for photodynamic therapy of cancers. [ABSTRACT FROM AUTHOR]

The P2X1 receptor is a trimeric ligand-gated ion channel that plays an important role in urogenital and immune functions, offering the potential for new drug treatments. However, progress in this area has been hindered by limited structural information and a lack of well-characterised tool compounds. In this study, we employ cryogenic electron microscopy (cryo-EM) to elucidate the structures of the P2X1 receptor in an ATP-bound desensitised state and an NF449-bound closed state. NF449, a potent P2X1 receptor antagonist, engages the receptor distinctively, while ATP, the endogenous ligand, binds in a manner consistent with other P2X receptors. To explore the molecular basis of receptor inhibition, activation, and ligand interactions, key residues involved in ligand and metal ion binding were mutated. Radioligand binding assays with [3H]-α,β-methylene ATP and intracellular calcium ion influx assays were used to evaluate the effects of these mutations. These experiments validate key ligand-receptor interactions and identify conserved and non-conserved residues critical for ligand binding or receptor modulation. This research expands our understanding of the P2X1 receptor structure at a molecular level and opens new avenues for in silico drug design targeting the P2X1 receptor. The P2X1 receptor is a promising target for the development of a non-hormonal male contraceptive. Here, researchers determined the atomic structure of the P2X1 receptor, revealing opportunities for developing drugs to target this receptor. [ABSTRACT FROM AUTHOR]

Ion channels play an important role in mediating pain through signal transduction, regulation, and control of responses, particularly in neuropathic pain. Transient receptor potential channel superfamily plays an important role in cation permeability and cellular signaling. Transient receptor potential channel Melastatin 2 (TRPM2) subfamily regulates Ca2+ concentration in response to various chemicals and signals from the surrounding environment. TRPM2 has a role in several physiological functions such as cellular osmosis, temperature sensing, cellular proliferation, as well as the manifestation of many disease processes such as pain process, cancer, apoptosis, endothelial dysfunction, angiogenesis, renal and lung fibrosis, and cerebral ischemic stroke. Toll-like Receptor 4 (TLR4) is a critical initiator of the immune response to inflammatory stimuli, particularly those triggered by Lipopolysaccharide (LPS). It activates downstream pathways leading to the production of oxidative molecules and inflammatory cytokines, which are modulated by basal and store-operated calcium ion signaling. The cytokine production and release cause an imbalance of antioxidant enzymes and redox potential in the Endoplasmic Reticulum and mitochondria due to oxidative stress, which results from TLR-4 activation and consequently induces the production of inflammatory cytokines in neuronal cells, exacerbating the pain process. Very few studies have reported the role of TRPM2 and its association with Toll-like receptors in the context of neuropathic pain. However, the molecular mechanism underlying the interaction between TRPM2 and TLR-4 and the quantum of impact in acute and chronic neuropathic pain remains unclear. Understanding the link between TLR-4 and TRPM2 will provide more insights into pain regulation mechanisms for the development of new therapeutic molecules to address neuropathic pain. [ABSTRACT FROM AUTHOR]

Ion interference including copper (Cu+)/calcium (Ca2+) overload activate cell‐specific death channels, damage mitochondria and disrupt cellular homeostasis, showing great potential in anti‐tumor therapy. However, the complex metabolic environment and the powerful self‐protection of tumors cause clinical failure of ion interference. Thus, metabolic disruption is expected an innovative strategy for the enhancement of ion interference. Herein, CuS‐α‐CHCA&penthiopyrad@CaCO3‐RGD nanoparticles (CCPCR NPs) are prepared to provide a Cu+/Ca2+ dual‐overload anti‐tumor therapy assisted by metabolic‐symbiosis‐destruction strategy, realizing the collapse of tumor self‐protection. Specifically, precise CuS and CaCO3 delivery triggered irreversible Cu+/Ca2+ dual‐overload and reactive oxygen species (ROS) attack toward 4T1 cells. Meanwhile, α‐CHCA and penthiopyrad disturbed the metabolic symbiotic environment by disrupting the TCA cycle and preventing lactate efflux to aggravate intracellular acidosis and promote Fenton‐like reaction of Cu+, enhancing the sensitivity of tumor cells to copper death and Ca2+ overload. Further, aided by the metabolism of symbiosis, the destroyed tumor cells further activate the polarization of M1 macrophages and the maturation and antigen cross‐presentation of dendritic cells (DCs), which further eliminate tumor cells. In summary, an amplified anti‐tumor dual‐ion interference strategy assisted by metabolic symbiotic destruction is established, which is of great significance in improving the clinical effect of ion therapy for tumors. [ABSTRACT FROM AUTHOR]

• TMAS enhances spatial learning and memory abilities and novelty-seeking desire in mice. • Real-time TMAS promotes neural signal transmission in the hippocampal CA1 region of mice. • After TMAS, hippocampal CA1 neurons remain active for a period of time. • TMAS does not cause excessive anxiety in mice. As a new means of brain neuroregulation and research, transcranial magneto-acoustic stimulation (TMAS) uses the coupling effect of ultrasound and a static magnetic field to regulate neural activity in the corresponding brain areas. Calcium ions can promote the secretion of neurotransmitters and play a key role in the transmission of neural signals in brain cognition. In this study, to explore the effects of TMAS on cognitive function and neural signaling in the CA1 region of the hippocampus, TMAS was applied to male 2-month-old C57 mice with a magnetic field strength of 0.3 T and ultrasound intensity of 2.6 W/cm2. First, the efficiency of neural signaling in the CA1 region of the mouse hippocampus was detected by fiber photometry. Second, the effects of TMAS on cognitive function in mice were investigated through multiple behavioral experiments, including spatial learning and memory ability, anxiety and desire for novelty. The experimental results showed that TMAS could improve cognitive function in mice, and the efficiency of neural signaling in the CA1 area of the hippocampus was significantly increased during stimulation and maintained for one week after stimulation. In addition, the neural signaling efficiency in the CA1 area of the hippocampus increased in the open field (OF) experiment and recovered after one week, the neural signaling efficiency in the new object exploration (NOE) experiment was significantly enhanced, and the intensity slowed after one week. In conclusion, TMAS enhances cognitive performance and promotes neural signaling in the CA1 region of the mouse hippocampus. [ABSTRACT FROM AUTHOR]

In this study, peptide‐calcium chelate was screened from antler bone hydrolysate, and its bioactivity on MC3T3‐E1 cells and its chelating mechanism were investigated. In vitro experiments showed that peptide‐calcium chelate promoted the differentiation and mineralization of MC3T3‐E1 cells. Subsequently, three novel calcium‐chelating peptides were obtained from antler bone hydrolysate using hydroxyapatite chromatography (HAC), Sephadex G‐25 gel filtration chromatography, and reversed‐phase high‐performance liquid chromatography (RP‐HPLC). Meanwhile, this work determined peptides' amino acid sequences as TKLGTQLQL, LETVILGLLKT, and KMVFLMDLLK based on LC–MS/MS. Then the present work prepared the three peptides, with the corresponding calcium‐chelating rates being verified as 87.68 ± 2.86%, 80.72 ± 0.93%, and 67.96 ± 0.98%, respectively. Fourier transform infrared (FTIR) spectroscopy, ultraviolet–visible absorption (UV–vis) spectroscopy, X‐ray diffraction (XRD), circular dichroism (CD), zeta potential, and molecular dynamics (MD) simulations were adopted to investigate the chelating mode of peptides with calcium ions. As a result, oxygen in the carboxyl group and the nitrogen in the amino group were related to calcium binding. In addition, the chelation site preferred the negatively charged carboxylate groups of Leu or Thr. The present work revealed that antler bone might be the new calcium‐chelating peptide source and elucidated their positive role in osteogenesis. [ABSTRACT FROM AUTHOR]

Background: The unique ability of the respiratory tract to protect the integrity of the airways by removing potentially harmful substances is defined as mucociliary clearance. This complex physiological mechanism protects the lower airways by ridding them of pollutants and pathogens. This study aimed to evaluate the potential influence of clinically relevant vasopressors on mucociliary clearance. Material and methods: The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance under the influence of dopamine, norepinephrine, and vasopressin. Inhibitory substances were applied to elucidate relevant signal transduction cascades and the value and origin of calcium ions. Reverse-transcription polymerase chain reactions (RTPCR) were performed to identify the expression of vasopressin receptor subtypes. Results: Dopamine, norepinephrine, and vasopressin significantly increased the PTV in a dose-dependent manner with half maximal effective concentrations of 0.58 µM, 1.21 µM, and 0.10 µM, respectively. Each substance increased the PTV via separate receptor pathways. While dopamine acted on D1-like receptors to increase the PTV, norepinephrine acted on β-adrenergic receptors, and vasopressin acted on V1a receptors. RT-PCR revealed the expression of V1a in the murine whole trachea and tracheal epithelium. PTV increased when protein kinase A was inhibited and norepinephrine or vasopressin were applied, but not when dopamine was applied. Phospholipase C inhibition decreased the PTV when vasopressin was applied. In general, maximum PTV was significantly reduced when extracellular calcium entry was inhibited. When intracellular calcium stores were depleted, no increase in PTV was observed after administering all three substances. Inositol trisphosphate receptor activation was found to be pivotal in the increase in murine PTV after applying dopamine and vasopressin. Discussion: Dopamine, norepinephrine, and vasopressin accelerate the murine PTV via substance-specific receptor pathways. Further investigations should assess the value and interaction of these substances on mucociliary clearance in clinical practice. [ABSTRACT FROM AUTHOR]

One of the key tissue movements driving closure of a wound is reepithelialisation. Earlier wound healing studies describe the dynamic cell behaviours that contribute to wound re-epithelialisation, including cell division, cell shape changes and cell migration, as well as the signals that might regulate these cell behaviours. Here, we have used a series of deep learning tools to quantify the contributions of each of these cell behaviours from movies of repairing wounds in the Drosophila pupal wing epithelium. We test how each is altered after knockdown of the conserved wound repair signals Ca2+ and JNK, as well as after ablation of macrophages that supply growth factor signals believed to orchestrate aspects of the repair process. Our genetic perturbation experiments provide quantifiable insights regarding how these wound signals impact cell behaviours. We find that Ca2+ signalling is a master regulator required for all contributing cell behaviours; JNK signalling primarily drives cell shape changes and divisions, whereas signals from macrophages largely regulate cell migration and proliferation. Our studies show deep learning to be a valuable tool for unravelling complex signalling hierarchies underlying tissue repair. [ABSTRACT FROM AUTHOR]

Anoctamin 6 (ANO6, TMEM16F) is a phospholipid (PL) scramblase that moves PLs between both plasma membrane (PM) leaflets and operates as an ion channel. It plays a role in development and is essential for hemostasis, bone mineralization and immune defense. However, ANO6 has also been shown to regulate cellular Ca2+ signaling and PM compartments, thereby controlling the expression of ion channels such as CFTR. Given these pleiotropic effects, we investigated the functional interdependence of the ubiquitous ANO6 with other commonly co-expressed anoctamins. As most expression studies on anoctamins use HEK293 human embryonic kidney cells, we compared ion currents, PL scrambling and Ca2+ signals induced by the overexpression of anoctamins in HEK293 wild-type parental and ANO6-knockout cells. The data suggest that the endogenous expression of ANO6 significantly affects the results obtained from overexpressed anoctamins, particularly after increasing intracellular Ca2+. Thus, a significant interdependence of anoctamins may influence the interpretation of data obtained from the functional analysis of overexpressed anoctamins. [ABSTRACT FROM AUTHOR]