Search Results (278)

Background/Objectives: Neutrophils express the receptor for advanced glycation end products (RAGE), yet its role in antibacterial responses remains incompletely defined. This study aims to elucidate the dual functionality of RAGE as a membrane-bound signaling sensor and a source of soluble RAGE (sRAGE) in human neutrophils challenged with Salmonella typhimurium, a clinically relevant Gram-negative pathogen. Methods: Human peripheral neutrophils from healthy donors were isolated and stimulated with S. typhimurium, LPS, or fMLP. Calcium flux, ROS/RNS production, and phagocytosis were assessed using fluorescent probes and spectroscopy. RAGE expression and localization were analyzed by immunofluorescence microscopy and flow cytometry. Soluble RAGE in supernatants was quantified by ELISA, and its molecular forms were characterized by Western blotting. Results: Resting neutrophils exhibited minimal surface RAGE but a substantial intracellular pool. RAGE inhibition with FPS-ZM1 attenuated bacteria-induced Ca²⁺ mobilization, oxidative burst, nitrosative output, and phagocytosis, with the most pronounced defect at the pathogen-attachment stage—consistent with impaired cytoskeletal remodeling. Upon activation, neutrophils rapidly released sRAGE (peak at ~10 min) via combined metalloprotease-dependent shedding and regulated secretion of pre-formed intracellular stores. Paradoxically, FPS-ZM1 amplified sRAGE release while suppressing membrane-proximal signaling. Conclusions: Neutrophil RAGE functions as a dynamic, multi-compartmental regulator: membrane-associated RAGE licenses effector responses to Gram-negative bacteria, while concomitant sRAGE release provides a fast negative-feedback loop to limit excessive inflammation. This self-limiting circuit balances antimicrobial defense with tissue protection, and its dysregulation may contribute to pathological outcomes in acute and chronic infections. Full article

Preterm labor is a major cause of neonatal morbidity and mortality and is frequently driven by infection-associated inflammation that promotes premature uterine activation. In this study, we investigated the effects of adipose stem cell-derived extracellular vesicles (ASC-EVs) on macrophage-mediated inflammatory signaling in uterine smooth muscle cells (HUtSMCs). An in vitro model was established by treating HUtSMCs with conditioned media derived from LPS-stimulated RAW264.7 macrophages. Activation of signaling pathways was assessed by Western blotting and immunofluorescence, and functional responses were evaluated using calcium flux and collagen gel contraction assays. Conditioned media from LPS-stimulated macrophages induced robust activation of MAPK (ERK1/2 and JNK) and NF-κB signaling, accompanied by IκB degradation and nuclear translocation of phosphorylated p65, whereas ASC-EVs pretreatment significantly attenuated these responses and reduced the expression of pro-inflammatory cytokines, including IL-6, IL-8, and MCP-1. Furthermore, macrophage-conditioned media enhanced intracellular calcium flux and contractile activity in HUtSMCs, both of which were suppressed by ASC-EVs. Inhibition of TLR4 signaling in macrophages reduced the inflammatory potency of conditioned media, indicating a key upstream role of macrophage TLR4 activation. Collectively, these findings demonstrate that ASC-EVs suppress macrophage-mediated inflammatory activation and downstream contractile responses, suggesting their potential as a cell-free therapeutic strategy for preventing inflammation-associated preterm labor. Full article

Using solid waste as supplementary cementitious materials (SCMs) is an effective strategy for promoting low-carbon construction development. However, single or binary systems often exhibit mismatched reaction kinetics, thereby limiting their performance at high cement replacement rates. This study focuses on a novel low-carbon concrete designed based on reaction sequence coordination, containing recycled brick powder (RBP), ground granulated blast-furnace slag (GGBS), and self-combusting coal gangue (SCCG). The effects of RBP, GGBS, and SCCG on the hydration process and microstructure of the novel low-carbon concrete with different replacement levels have been studied by testing compressive strength, workability, and durability and observing microstructural changes. The results showed that an optimized ternary composition with an RBP:GGBS:SCCG ratio of 4:3:1 achieves a cement replacement level of 30% while exhibiting a 28-day compressive strength of 38.26 MPa, representing a 14.2% increase compared with plain cement mortar. Microstructural analyses indicate that this enhanced performance results from a time-dependent reaction sequence, in which GGBS contributes predominantly at early ages by supplying calcium, whereas RBP and SCCG mainly participate through delayed pozzolanic reactions and pore refinement at later ages. Consequently, the optimized ternary mortar exhibits a water absorption of 11.12% and a 27.2% reduction in electrical flux. This study aims to provide practical strategies for enhancing the performance of low-carbon cementitious materials through a reaction sequence coordination design approach, thereby improving the utilization efficiency of solid waste in the production of low-carbon building materials. Full article

Salt stress poses a major environmental challenge that leads to ecological imbalance and reduced agricultural productivity globally. Sapium sebiferum, a highly valued ornamental and perennial woody oil species, shows promise for saline land utilization due to its natural salt stress adaptability. However, the underlying mechanisms remain largely unexplored. This study investigated the responses of S. sebiferum to salt stress by integrating RNA sequencing and Non-invasive Micro-test Technology (NMT). Comparative transcriptome analysis identified 693, 1061, and 1851 differentially expressed genes at 1 h, 3 h and 6 h after salt treatment, respectively. Functional analysis of DEGs revealed that genes related to ion binding, transmembrane transport, and signal transduction were significantly enriched. Notably, genes involved in calcium (Ca²⁺) and phytohormone signaling were altered, activating stress-response pathways. Furthermore, the dynamic effects of salt stress on nitrate (NO₃⁻) and ammonium (NH₄⁺) uptake were assessed. After salinity stress (150 mM NaCl), an increase in the net influx of NO₃⁻ was observed under the conditions of the assay, while the net flux of NH₄⁺ did not show a significant change. The differential expression of NRT genes suggests that NO₃⁻ may play a multifaceted role in salinity tolerance, potentially contributing to nutrition, ion homeostasis, and signaling pathways. The coordinated signaling network likely allows S. sebiferum to effectively cope with salinity stress and sustain physiological functions under challenging conditions. These findings provide valuable insights into the molecular basis of salt tolerance in S. sebiferum, thereby supporting sustainable practices in saline environments. Full article

Podocyte injury is a characteristic feature of focal segmental glomerulosclerosis (FSGS) that leads to the development of nephrosis as its loss causes proteinuria and progressive glomerulosclerosis. The physiological function of podocytes is critically dependent on proper intracellular calcium levels; an excess or shortage of calcium influx in these cells may result in foot process effacement, apoptosis, and nephron degeneration. A key protein responsible for the regulation of calcium flux is the canonical transient receptor potential 6 (TRPC6) expressed in podocytes. Several mutations in the TRPC6 gene have been associated with FSGS. Here we present a systematically optimized inducible FSGS model system in human induced pluripotent stem cells (hiPSCs). We generated and phenotypically characterized three transgenic hiPSC lines with regulatable overexpression of TRPC6 wild-type and FSGS-associated gain-of-function (GoF, P112Q) and loss-of-function (LoF, G757D) mutations. Moreover, these cell lines were differentiated into induced podocytes (ipodocytes). We assessed the impact of TRPC6 GoF and LoF mutants on calcium influx in combination with TRPC6 agonists and antagonists. Our data showed relative calcium responses consistent with the GoF and LoF phenotypes. Transgenic iPSC-based models, like the one presented here, are instrumental to studying disease mechanisms in vitro and investigating the outcomes of, and possible therapeutic interventions for, this complex disease. Full article

Industrial activities have caused heavy metals, such as cadmium (Cd), chromium (Cr), lead (Pb), and copper (Cu), to seriously threaten groundwater safety through seepage pathways. This study explored the formation of biofilms using microbe-induced calcium carbonate precipitation (MICP) technology to simultaneously reduce seepage in contaminated water and immobilize heavy metals. By optimizing the cementation fluid concentration and the intermittent grouting time, the optimal operating conditions for forming a biofilm were determined to be 1.5 mol/L cementation fluid and an intermittent time of 12 h, under which the stable infiltration rate of the sandy loam soil column can be reduced by more than 80%. We found that this biofilm can effectively inhibit the convective transport of Cd, Cr, Pb, and Cu, with the cumulative convective flux reduction rates reaching 56.25%, 56.25%, 54.54%, and 55.59%, respectively. SEM and XRD analysis indicate that the physical blockage of soil pores by calcium carbonate crystals is the dominant mechanism controlling infiltration flow, while the detection of new mineral phases, such as lead carbonate (PbCO₃), cadmium carbonate (CdCO₃), and basic copper carbonate (Cu₂(OH)₂CO₃) provides direct evidence for the chemical co-precipitation immobilization of heavy metals. This study demonstrates that MICP biofilm is a green and sustainable technology for in situ remediation of heavy metal pollution through physical–chemical synergistic effects, offering a promising alternative with a lower environmental footprint compared to conventional methods. Full article

Light quality is a critical regulatory factor for the growth and nutritional quality of hydroponic lettuce (Lactuca sativa L.), and red–blue combined light serves as a key artificial light source for protected horticulture. This study aimed to investigate the effects of different red–blue (R:B) light ratios on the growth, photosynthetic pigment content, nutritional quality, antioxidant capacity, and mineral nutrient content and accumulation of hydroponic lettuce. Lettuce was cultivated under four R:B light treatments (CK: pure red light, 100:0; T1: 90:10; T2: 80:20; and T3: 60:40) with a uniform photosynthetic photon flux density of 350 µmol m⁻²s⁻¹ and a 12 h photoperiod. The results showed that all red–blue combined light treatments significantly improved the above physiological and nutritional indices compared with monochromatic red light (CK), with the fresh weight increased by 0.73 to 0.78 times and different R:B ratios inducing distinct tissue-specific and element-specific responses in lettuce. Specifically, T3 (60:40) exhibited the highest root dry weight (0.57 ± 0.02 g plant⁻¹), inhibited excessive leaf elongation to form a compact plant architecture, and its chlorophyll a and b contents increased significantly by 1.6 and 2.25 times compared with CK, respectively. Furthermore, T3 markedly enhanced the accumulation of soluble sugar (0.36 times higher), soluble protein (1.16 times higher), and vitamin C (4.09 times higher), reduced the nitrate content to 0.58 times that of CK, and showed the highest antioxidant capacity (polyphenol content and DPPH free radical scavenging rate), with antioxidant traits positively correlated with the blue light proportion. In contrast, T2 (80:20) effectively promoted plant biomass accumulation and exhibited the most balanced mineral nutrient profile, with significant increases in nitrogen, calcium, and magnesium accumulation, and it also upregulated chlorophyll synthesis to enhance carbon assimilation. T1 (90:10) had moderate regulatory effects on both lettuce growth and nutritional quality and was favorable for potassium accumulation in lettuce tissues. These findings clarify the differential regulatory mechanisms of red–blue light ratios on hydroponic lettuce and provide a theoretical basis for the precise configuration of LED lighting in greenhouse lettuce production. Lettuce producers can select specific R:B ratios according to actual cultivation demands, and the regulatory effects of such light ratios on red leaf lettuce varieties merit further exploration. Full article

Background: Fusion-negative rhabdomyosarcoma (FNRMS) represents the most prevalent subtype of rhabdomyosarcoma, the most common pediatric soft-tissue sarcoma. Although its invasion is a leading cause of recurrence and poor prognosis, its underlying mechanism remains unclear. We investigated how extracellular matrix density regulates FNRMS progression via mechano-transduction. Methods: We used three-dimensional spheroid invasion assays with FNRMS cells embedded in varying collagen concentrations. Mechanistic insights were gained through immunofluorescence, sequencing reanalysis, calcium live-cell imaging, and pharmacological inhibition of the YAP–PIEZO1 axis. Results: High extracellular matrix density significantly enhanced invasive spreading, correlating with increased YAP nuclear localization. YAP overexpression was sufficient to promote invasive spreading, while its inhibition attenuated the matrix-enhanced phenotype. We identified PIEZO1 as a direct transcriptional target of YAP. High extracellular matrix density stimulated PIEZO1-dependent calcium influx, which was required for invasion. Furthermore, elevated PIEZO1 expression was significantly associated with poorer overall survival in FNRMS patients. Targeting YAP effectively suppressed both calcium flux and invasion. Conclusions: Our findings establish a YAP–PIEZO1 axis linking extracellular matrix density to FNRMS invasion. This mechanosensitive pathway represents a potential therapeutic vulnerability in aggressive FNRMS. Full article

Salivary glands produce saliva through precisely coordinated epithelial ion transport processes. Ion channels are essential components of the molecular machinery that convert neural and hormonal signals into targeted ion and water flux. This review focuses on the integrated molecular and cellular mechanisms by which ion channels cooperate to generate salivary fluid under physiological conditions. Saliva formation proceeds through two sequential stages: isotonic primary fluid secretion by acinar cells, followed by ionic modification within the ductal epithelium. Parasympathetic stimulation activates muscarinic M1/3 receptors, initiating intracellular calcium signaling through inositol 1,4,5-trisphosphate-dependent release from the endoplasmic reticulum and sustained calcium entry via Orai1/TRPC channels. Elevated cytosolic calcium activates apical ANO1/TMEM16A chloride channels, the rate-limiting step in acinar fluid secretion, together with basolateral calcium-activated potassium channels that preserve the electrochemical driving force for chloride efflux. Chloride accumulation is maintained by Na⁺/K⁺-ATPase and the Na⁺-K⁺-2Cl⁻ cotransporter, while osmotic gradients drive water movement through apical aquaporin-5 and basolateral aquaporin-1/3. As primary saliva traverses the ductal system, epithelial sodium channels, CFTR, and additional ion transport pathways reabsorb sodium and chloride and secrete potassium and bicarbonate, producing hypotonic final saliva. By synthesizing calcium signaling, chloride and potassium conductance, sodium handling, and epithelial polarity into a unified framework, this review establishes ion channel integration as the fundamental basis of salivary gland fluid secretion. Full article

Mitochondria govern energy transfer, redox balance, and cell fate. Tryptophan catabolism generates kynurenines (KYNs) that can tune mitochondrial function, with growing evidence that G protein-coupled receptor 35 (GPR35), aryl hydrocarbon receptor (AhR), and N-methyl-D-aspartate receptors (NMDA receptors) link extracellular cues to adenosine 5 prime triphosphate (ATP) maintenance, calcium (Ca²⁺) handling, mitophagy, and inflammasome control. In parallel, quinolinic acid (QA)-driven de novo nicotinamide adenine dinucleotide (NAD⁺) synthesis connects KYN flux to tricarboxylic acid (TCA) cycle activity and sirtuin programs across tissues. Key gaps remain: receptor pharmacology is rarely integrated with NAD⁺ economics and respiration, and clinical workflows still lack single-run assays that quantify both kynurenine and TCA nodes. We therefore integrate receptor proximal signaling, QA-driven NAD⁺ supply, and unified liquid chromatography–mass spectrometry (LC-MS) measurement into one translational framework spanning kynurenic acid (KYNA), KYN, 3-hydroxykynurenine (3-HK), and QA, using mitochondrial endpoints as the common readout. We synthesize evidence for mitochondrial GPR35 signaling that preserves ATP, AhR programs that tune oxidative defenses and mitophagy, and NMDA receptor antagonism that limits excitotoxic stress. These mechanisms are linked to QA-dependent NAD⁺ biogenesis and alpha ketoglutarate control points, then aligned with chromatography and ionization choices suited to routine LC-MS workflows. This receptor to organelle framework couples KYN flux to respiratory control and provides a practical roadmap for standardized single-run LC-MS panels. It can strengthen target validation in ischemia, neurodegeneration, psychiatry, and oncology while improving biomarker qualification through harmonized analytics and decision-grade readouts. Full article

This study investigated the effects of calcium carbide slag (CCS) (0–12 wt%) incorporation on the workability, electrochemical properties, durability, and microstructure evolution of sulfoaluminate cement (SAC) mortar. Results showed that increasing CCS content reduced mortar fluidity and shortened setting time, indicating that CCS accelerates early hydration. A 9% CCS content was determined to be the optimal dosage; at 28 days, compared to the control group, this dosage group exhibited a 6.53% increase in compressive strength, a 22.47% decrease in drying shrinkage, and a 0.279% decrease in mass loss. These performance improvements stemmed from CCS’s ability to inhibit pore connectivity and limit moisture migration. Electrochemical analysis further revealed that the 9% CCS dosage group had the highest charge transfer resistance and resistivity (30.00% higher than the control group), reflecting a denser matrix and greater ion transport resistance. Consequently, chloride ion permeability was significantly reduced, with electrical flux and diffusion coefficient decreasing by 39.98% and 28.89%, respectively. Microstructural observations confirmed that CCS promotes the formation and densification of hydration products, effectively improving the internal pore structure. While 9% CCS can serve as an effective functional supplementary material, its long-term durability and sustainability still face practical application challenges. Future research should focus on establishing predictive models for chloride ion permeation lifetime and conducting quantitative sustainability assessments of CCS-SAC composites, particularly evaluating material cost, energy consumption, and carbon dioxide emissions. Full article

This study investigates the reaction thermodynamics of the sodium oxide-fluxed aluminothermic reduction of pyrolusite-based manganese ore under self-propagating high-temperature synthesis (SHS) conditions, using Si, Cr, and Cu as collector metals. The experimental results are compared with thermochemical equilibrium calculations using FactSage 7.3 thermochemistry software. Experimental mixtures were prepared with controlled additions of aluminium, sodium silicate, calcium oxide, and collector metals and heated to the ignition temperature in a muffle furnace preheated to 1350 °C. The resulting alloys and slags were analysed for bulk composition. Collector metals significantly influence alloy carbon saturation and manganese recovery. The individual reaction’s Gibbs free energy values and the gas–slag–metal equilibrium were calculated. Discrepancies between the experimental and equilibrium-predicted results highlight the kinetic factors of SHS processes, particularly with respect to aluminium uptake and manganese volatilisation. The main difference is the alloy’s aluminium uptake. The difference between the calculated and experimental aluminium levels is, in part, due to the higher partial oxygen pressure predicted in the gas–slag–metal equilibrium calculations, compared with that of the likely Al–Al₂O₃ governing reaction equilibrium. Short-circuiting of aluminium to the alloy is also a possible contributing factor. The findings provide insights into optimising feed formulations and process parameters for improved manganese recovery. Full article

Natural compounds have experienced increasing clinical application, but their association with rapid-onset anaphylactoid reactions (ARs) present a significant challenge to their safe use. These ARs, clinically resembling Type I hypersensitivity, are non-IgE-mediated and involve direct mast cell activation, primarily through the human Mas-related G protein-coupled receptor X2 (MRGPRX2). We computationally screened a natural compound library for MRGPRX2 activation. A human MRGPRX2-expressing cell model was established. Cell viability assays (0–80 μM) were performed to determine appropriate drug concentrations. Compared to the controls, Baohuoside I (10 μM), along with Kaempferol-3-O-rutinoside, Epigallocatechin gallate (EGCG), Isochlorogenic Acid B, Baicalin, Andrographolide, Isorhamnetin, and Dehydroandrographolide (all at 20 μM), significantly increased intracellular calcium flux (p < 0.05) and boosted tryptase and β-hexosaminidase secretion (ELISA) (p < 0.05) in mast cells. Furthermore, the degranulation induced by these compounds was inhibited by the MRGPRX2 inhibitor Z3578 at 20 μM. Neutral red staining was employed to observe cellular morphological changes. Specific compounds capable of mediating ARs through MRGPRX2 activation on mast cells were identified. This contributes to safer and more effective drug use by elucidating the potential triggers of ARs. Full article

Asthma is a heterogeneous disease that varies in clinical presentation, severity, and underlying biology but consistently involves airway remodeling (AR) and airway hyperresponsiveness (AHR), which is characterized by excessive airway narrowing in response to various stimuli. Airway smooth muscle (ASM) cells are primary contributors to airway hyperresponsiveness and bronchoconstriction. This review focuses on ASM cells and their role in asthma. We discuss the mechanisms by which ASM mediates AHR, increases airway thickness, and contributes to AR. Signaling through G protein-coupled receptors (GPCRs) regulates many ASM functions, including contraction, growth, and the synthetic activities that drive airway inflammation and remodeling. GPCR-dependent calcium flux serves as a key signaling axis controlling the contractile responses of ASM. Here we provide a comprehensive summary of the major GPCRs as well as other non-GPCRs identified in ASM cells. GPCR-induced calcium mobilization, downstream signaling and how it has been linked to specific ASM functions are also discussed. Furthermore, we highlight the clinical significance of targeting GPCRs in asthma therapy as well as recent development of novel therapeutics in the management of asthma. Thus, this review provides a comprehensive overview of airway smooth muscle in the context of asthma pathophysiology. Full article

Lithium is an essential material for lightweight batteries. Traditional mining of soluble salts expanded to include the extraction of hard rocks, which requires their solubilization through roasting. Among hard lithium rocks, spodumene has recently received attention from the scientific community. Its metallurgical processing can be classified according to the type of reagents, as well as the operating temperature and pressure. The use of calcium carbonate as a natural alkali avoids aggressive chemicals such as sulfuric acid or caustic soda. In this article, 0.5 g of jewelry-grade spodumene was loaded into a ceramic crucible with 2.5 g of reducing agent in a tandem of roasting at 1050 °C-1 bar-30 min and leaching with neutral water at 90 °C-1 bar-20 min at a water/clinker mass ratio of 25. Measurements by XRD, ICP-OES, and SEM-EDX suggest a pathway of spodumene cracking because of poor contact with the reductant. Potassium present in the crucible acts as a flux and encapsulates spodumene crystals, causing lithium to end up bound to silica. While lithium metasilicate is barely soluble in water, leaching potassium aluminate hoards in the liquid. The empirical observations were supported with thermodynamic spontaneity studies, which required compiling the mineral properties based on open reference tabulations. Full article