Search Results (265)

Increased epithelial and endothelial permeability, along with dysregulated inflammatory responses, are key aspects of acute respiratory distress syndrome (ARDS) pathophysiology, which not only impact the lungs but also contribute to detrimental organ crosstalk with distant organs, ultimately leading to multiple organ dysfunction syndrome (MODS)—the primary cause of morbidity and mortality in patients with lung injury (LI) and ARDS. It is predominantly manifested by hypoxemic respiratory failure and bilateral pulmonary infiltrates, which cannot be fully attributed to cardiac failure or hypervolemia, but rather to alveolo-capillary barrier dysfunction, dysregulated systemic and pulmonary inflammation, immune system abnormalities, and mechanical stimuli-related responses. However, these pathological features are not uniform among patients with ARDS, as distinct subphenotypes with unique biological, clinical, physiological, and radiographic characteristics have been increasingly recognized in recent decades. The severity of ARDS, clinical outcomes, mortality, and efficacy of applied therapeutic measures appear significant depending on the respective phenotype. Acknowledging the heterogeneity of ARDS and defining distinct subphenotypes could significantly modify therapeutic strategies, enabling more precise and targeted treatments. To address these issues, a comprehensive literature search was conducted in PubMed using predefined keywords related to ARDS pathophysiology, subphenotypes, and personalized therapeutic approaches. Optimizing the identification and characterization of discrete ARDS subphenotypes—based on clinical, biological, physiological, and radiographic criteria—will deepen our understanding of ARDS pathophysiology, promote targeted recruitment in prospective clinical studies to define patient clusters with heterogeneous therapeutic responses, and support the shift toward individualized treatment strategies. Full article

Acute lung injury (ALI), a life-threatening clinical syndrome with multifactorial origins, is characterized by uncontrolled pulmonary inflammation and disrupted alveolar–capillary barrier integrity, leading to progressive hypoxemia and respiratory failure. In this hypoxic setting, hypoxia-inducible factor (HIF)-1 is activated, acting as a central regulator of the inflammatory response and reparative processes in injured lung tissue during ALI. The role of HIF-1 is distinctly dualistic; it promotes both anti-inflammatory and reparative mechanisms to a certain extent, while potentially exacerbating inflammation, thus having a complex impact on disease progression. We explore the latest understanding of the role of hypoxia/HIF-mediated inflammatory and reparative pathways in ALI and consider the potential therapeutic applications of drugs targeting these pathways for the development of innovative treatment strategies. Therefore, this review aims to guide future research and clinical applications by emphasizing HIF-1 as a key therapeutic target for ALI. Full article

Carbon dioxide (CO₂) geosequestration is a critical technology for reducing greenhouse gas emissions, with shale caprocks, such as Opalinus Clay (OPA), serving as essential seals to prevent CO₂ leakage. This study employs computational fluid dynamics and finite element analysis to investigate the hydromechanical behavior of OPA during CO₂ injection, integrating qualitative and quantitative insights. Validated numerical models indicate that capillary forces are the most critical factor in determining the material’s reaction, with an entry capillary pressure of 2–6 MPa serving as a significant threshold for CO₂ breakthrough. The numbers show that increasing the stress loading from 5 to 30 MPa lowers permeability by 0.3–0.45% for every 5 MPa increase. Porosity, on the other hand, drops by 9.2–9.4% under the same conditions. The OPA is compacted, and axial displacements confirm numerical models with an error margin of less than 10%. Saturation analysis demonstrates that CO₂ penetration becomes stronger at higher injection pressures (8–12 MPa), although capillary barriers slow migration until critical pressures are reached. These results demonstrate how OPA’s geomechanical stability and fluid dynamics interact, indicating that it may be utilized as a caprock for CO₂ storage. The study provides valuable insights for enhancing injection techniques and assessing the safety of long-term storage. Full article

Background: Salmonella infections impose a substantial global health burden, with an estimated 95.1 million cases occurring annually. Pregnant women exhibit a heightened vulnerability due to pregnancy-specific immune adaptations and dietary habits that increase their risk of Salmonella exposure, facilitating possible damage to the placental barrier. Despite this significant burden, Salmonella-associated placental pathology remains poorly understood, particularly its impact on foetal development through microstructural alterations. Aim: This study utilised stereology to assess histomorphological and functional alterations in term placentae of Salmonella Typhi-exposed placentae, compared to unexposed controls. Methods: A hospital-based case-control study was conducted in Ghana. Of 237 screened women, 62 placentae were selected for analysis, comprising 31 Salmonella-exposed cases (IgG/IgM-positive in placental and cord blood) and 31 gestational age-matched controls (IgG/IgM-negative). Placental tissues were processed for histology and stereology. Neonatal birthweights were also compared. Results: Stereological assessment revealed significantly higher mean volume densities of syncytial knots in the study group (0.4755 ± 0.04) compared to the controls (0.3342 ± 0.04, p = 0.0219). Syncytial denudation was increased in the study group (0.8113 ± 0.09) relative to the controls (0.1975 ± 0.08, p < 0.0001). Foetal capillary volume density was also significantly elevated in the study group (5.1010 ± 0.32) compared to the controls (3.562 ± 0.47, p < 0.0001). In contrast, intervillous space volume was significantly reduced in the study group (9.5810 ± 0.05) compared to the controls (11.593 ± 0.26, p = 0.0053). Neonates of exposed mothers showed a non-significant reduction in birthweight. Conclusion: Salmonella Typhi exposure in pregnancy induces subtle, yet significant alterations in placental architecture, compromising villous integrity and vascular organisation. Although birthweight may appear unaffected, the observed changes point to reduced placental efficiency and merit further research into their developmental consequences and long-term effects on babies. Full article

The crystallization of soluble salts is one of the most significant agents of deterioration affecting porous building materials in historical architecture. This process not only compromises the physical integrity of the materials but also results in considerable aesthetic, structural, and economic consequences. Soluble salts involved in these processes may originate from geogenic sources—including soil leachate, marine aerosols, and the natural weathering of parent rocks—or from anthropogenic factors such as air pollution, wastewater infiltration, and the use of incompatible restoration materials. This study examines the role of capillary rise as a primary mechanism responsible for the vertical migration of saline solutions from the soil profile into historic masonry structures, especially those constructed with calcareous stones. It describes how water retained or sustained within the soil matrix ascends via capillarity, carrying dissolved salts that eventually crystallize within the pore network of the stone. This phenomenon leads to a variety of damage types, ranging from superficial staining and efflorescence to more severe forms such as subflorescence, microfracturing, and progressive mass loss. By adopting a multidisciplinary approach that integrates concepts and methods from soil physics, hydrology, petrophysics, and conservation science, this paper examines the mechanisms that govern saline water movement, salt precipitation patterns, and their cumulative effects on stone durability. It highlights the influence of key variables such as soil texture and structure, matric potential, hydraulic conductivity, climatic conditions, and stone porosity on the severity and progression of deterioration. This paper also addresses regional considerations by focusing on the context of Spain, which holds one of the highest concentrations of World Heritage Sites globally and where many monuments are constructed from vulnerable calcareous materials such as fossiliferous calcarenites and marly limestones. Special attention is given to the types of salts most commonly encountered in Spanish soils—particularly chlorides and sulfates—and their thermodynamic behavior under fluctuating environmental conditions. Ultimately, this study underscores the pressing need for integrated, preventive conservation strategies. These include the implementation of drainage systems, capillary barriers, and the use of compatible materials in restoration, as well as the application of non-destructive diagnostic techniques such as electrical resistivity tomography and hyperspectral imaging. Understanding the interplay between soil moisture dynamics, salt crystallization, and material degradation is essential for safeguarding the cultural and structural value of historic buildings in the face of ongoing environmental challenges and climate variability. Full article

Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s therapeutic mechanisms against cholestasis, with a focus on the gut microbiota-mediated regulation of the farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) pathway. Methods: An alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis mouse model was established. Mice received YCHD (3/9 g/kg) for 7 days. 16S rRNA sequencing, targeted LC/MS (bile acid (BA) quantification), untargeted GC/MS (fecal metabolite detection), qPCR/Western blot (FXR pathway analysis), fecal microbiota transplantation (FMT), and antibiotic depletion were employed to dissect the gut–liver axis interactions. Results: YCHD alleviated cholestatic liver injury by reducing serum biomarkers, restoring BA homeostasis via FXR-FGF15 activation, and suppressing hepatic Cyp7a1-mediated BA synthesis. It remodeled gut microbiota, enriched FXR-activating secondary BAs (CDCA, DCA, CA), and restored the intestinal barrier integrity. Antibiotic cocktail abolished YCHD’s efficacy, while FMT from YCHD-treated mice enhanced its therapeutic effects, confirming microbiota dependency. Conclusions: YCHD mitigates cholestasis through gut microbiota-driven FXR activation and direct hepatobiliary regulation. These findings bridge traditional medicine and modern pharmacology, highlighting microbiome modulation as a therapeutic strategy for cholestatic liver diseases. Full article

An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of Pseudechis papuanus (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as observed histologically and by analysis of bronchoalveolar lavage fluid (BALF). In parallel, venom induced an increase in all of the pulmonary mechanical parameters evaluated, without causing major effects in terms of tracheal and bronchial reactivity. These effects were abrogated by incubating the venom with the PLA₂ inhibitor varespladib, indicating that this hydrolytic enzyme is responsible for these alterations. The venom was cytotoxic to endothelial cells in culture, hydrolyzed phospholipids of a pulmonary surfactant, and reduced the activity of angiotensin-converting enzyme in the lungs. The pretreatment of mice with the nitric oxide synthase inhibitor L-NAME reduced the protein concentration in the BALF, whereas no effect was observed when mice were pretreated with inhibitors of cyclooxygenase (COX), tumor necrosis factor-α (TNF-α), bradykinin, or neutrophils. Based on these findings, it is proposed that the rapid pathological effect of this venom in the lungs is mediated by (a) the direct cytotoxicity of venom PLA₂ on cells of the capillary–alveolar barrier, (b) the degradation of surfactant factor by PLA₂, (c) the deleterious action of nitric oxide in pulmonary tissue, and (d) the cytotoxic action of free hemoglobin that accumulates in the lungs as a consequence of venom-induced intravascular hemolysis. Our findings offer clues on the mechanisms of pathophysiological alterations induced by PLA₂s in a variety of pulmonary diseases, including acute respiratory distress syndrome (ARDS). Full article

Perfusable microvasculature is critical for advancing in vitro tissue models, particularly for neural applications where limited diffusion impairs organoid growth and fails to replicate neurovascular function. This study presents a versatile fabrication platform that integrates mesh-driven design, two-photon lithography (TPL), and modular interfacing to create multi-material, perfusable 3D microvasculatures. Various 2D and 3D capillary paths were test-printed using both polygonal and lattice support strategies. A double-layered capillary scaffold based on the Hilbert curve was used for comparative materials testing. Methods for printing rigid (OrmoComp), moderately stiff hydrogel (polyethylene glycol diacrylate, PEGDA 700), and soft elastomeric (photocurable polydimethylsiloxane, PDMS) materials were developed and evaluated. Cone support structures enabled high-fidelity printing of the softer materials. A compact heat-shrink tubing interface provided leak-free perfusion without bulky fittings. Physiologically relevant flow velocities and Dextran diffusion through the scaffold were successfully demonstrated. Cytocompatibility assays confirmed that all TPL-printed scaffold materials supported human neural stem cell viability. Among peripheral components, lids fabricated via fused deposition modeling designed to hold microfluidic needle adapters exhibited good biocompatibility, while those made using liquid crystal display-based photopolymerization showed significant cytotoxicity despite indirect exposure. Overall, this platform enables creation of multi-material microvascular systems facilitated by TPL technology for complex, 3D neurovascular modeling, blood–brain barrier studies, and integration into vascularized organ-on-chip applications. Full article

The spleen plays a critical role in the immune and hematopoietic systems of teleost fish, functioning as a major secondary lymphoid organ. This study provides a detailed morphological and ultrastructural assessment of the spleen in goldfish (Carassius auratus), focusing on its immunological organization and cellular diversity. Through light and transmission electron microscopy, we examined red and white pulps, identifying key features such as melanomacrophage centers (MMCs), ellipsoids, and various immune cell types. The red pulp was rich in sinusoidal capillaries and splenic cords, whereas the white pulp housed lymphocytes, dendritic cells, macrophages, and telocytes, all contributing to immune regulation. Notably, ellipsoids were surrounded by reticular and macrophage sheaths, forming a filtration barrier against pathogens. Ultrastructural analysis revealed diverse immune cells with active morphological traits, including macrophages with pseudopodia and pigment granules, dendritic cells with dendrite-like extensions, and epithelial reticular cells involved in forming the blood–spleen barrier. These findings highlight the complex immunological microarchitecture of the goldfish spleen and its functional relevance in teleost immune responses. Full article

Pathophysiological differences separating small vessel disease (SVD) from Alzheimer’s disease (AD) may alter treatment approach. Investigating peak-arterial and late-capillary perfusion may differentiate SVD from AD. 14 Subjects with MoCA scores of 11–24 were divided into 2 groups. Group one: 6 AD likely subjects positive for 1 or 2 copies of APOE 4+. Group two: 8 SVD likely subjects APOE−. Group three: 7 age-matched controls (MoCA 26–30). All underwent 3D PASL MRI, FLAIR, and SWI axial MRI. Arterial phase peak amplitude and latency, late capillary inflow/clearance rates, and anatomic abnormalities quantitated using microhemorrhage count, Fazekas, Koedam, and Schelton scales were compared. Arterial perfusion demonstrated no statistical differences among SVD, AD, and controls, suggesting normal arterial flow. Late phase perfusion showed significant localized reduction in capillary flow/clearance rates in SVD and AD compared to controls. Absent arterial phase but significant capillary inflow/clearance differences from controls suggest SVD and AD share common impaired blood–brain barrier origins. Full article

Background: Idiopathic intracranial hypertension (IIH) is, by definition, of unknown cause. Davson’s equation indicates that the increased intracranial pressure (ICP) found in IIH could be due to an increase in the CSF formation rate (CSF_fr), the CSF outflow resistance (R_out) or the venous sinus pressure. Studies simultaneously measuring the ICP and sagittal sinus pressures in IIH suggest that there is either a reduction in the R_out and/or the CSF_fr. The latter suggests that the increased venous pressure can be the only variable causing this disease process. A study maintaining the ICP at zero showed a significantly elevated CSF_fr in this disease. The purpose of the current study is to define the most feasible explanation for these findings and to suggest a viable pathophysiology for IIH. Methods: A lumped parameter vascular model, originally developed to study normal pressure hydrocephalus, was extended to investigate IIH. The model used the simultaneously obtained ICP and sagittal sinus pressure measurements from five experiments published in the literature to estimate the CSF_fr and the capillary transmural pressure (TMP). The assumptions made during this study were those of a normal mean arterial pressure, a normal total R_out and a normal blood flow rate. Results: When the CSF formation rates were plotted against the estimated capillary transmural pressures, a straight line was returned, suggesting that the CSF_fr and capillary TMP are related. Conclusions: The novel findings of this study suggest that the CSF_fr in IIH varies with the capillary TMP. A reduced capillary TMP in IIH can moderate the ICP if there is net CSF absorption across the capillaries. This would require the blood–brain barrier (BBB) to be disrupted. The model suggests that drugs which stabilise the BBB may trigger IIH by blocking CSF absorption across the capillaries, increasing the apparent CSF formation rate back toward normal and increasing the ICP. Anaemia will promote IIH by increasing the cerebral blood flow, the capillary TMP and the CSF_fr. Full article

Objectives: In this study, we investigated the effects of intravenous glutamine (GLN) administration on the Toll-like receptor 3 (TLR3) antiviral pathway and leukocyte migration in mice with poly(I:C)-induced acute lung injury (ALI). Methods: There were four groups in this study: the NC group, mice without an intratracheal injection; the SH group, mice intratracheally injected with endotoxin-free saline; the PS group, intratracheally instilled with 3 mg poly(I:C)/kg body weight (BW), followed by an intravenous (IV) injection of saline; and the PG group, intratracheally injected with poly(I:C) followed by the IV administration of 0.75 g GLN/kg BW. Mice in the SH, PS, and PG groups were sacrificed at 4, 12, and 24 h after intratracheal instillation. Results: The results showed that poly(I:C) stimulation decreased the plasma GLN concentration and increased inflammatory cytokine levels. In bronchoalveolar lavage fluid, concentrations of interferon λ3 and percentages of macrophages and M1 macrophages decreased, while neutrophils increased along with significantly elevated myeloperoxidase activity in lung tissues. The gene expressions of molecules related to leukocyte migration increased, whereas tight/adherens junction expressions in endothelial and epithelial cells were reduced. GLN supplementation upregulated the mRNA and/or protein expressions of TLR3 antiviral pathway-related factors and tight/adherens junctions while reducing inflammatory cytokines and the expressions of leukocyte migration molecules. Histological results also showed that lung injury was attenuated. Conclusions: These findings indicated that intravenous GLN administration after poly(I:C) instillation restored plasma GLN levels and alleviated ALI by activating the TLR3 antiviral pathway, suppressing leukocyte migration and neutrophil infiltration, mitigating inflammation, and improving the integrity of the alveolar–capillary barrier. Full article

Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) pathology and is closely linked to oxidative stress, which contributes to blood–brain barrier leakage, renal dysfunction, and cognitive decline. We investigated the effects of N-acetyl cysteine (NAC), an FDA-approved antioxidant, on oxidative stress, brain Aβ levels, barrier leakage, renal function, and cognition in 5xFAD mice. Eight-week-old 5xFAD mice were fed a rodent diet supplemented with 600 mg/kg_Diet NAC for 4 weeks; wild-type (WT) mice and control 5xFAD mice were fed a regular rodent diet. We detected elevated brain and renal 4-hydroxynonenal(4-HNE) levels, reduced creatinine clearance, and increased plasma S100β levels in untreated 5xFAD mice compared to WT controls. Untreated 5xFAD mice also had higher capillary leakage, reduced P-gp activity, and impaired cognition compared to WT. NAC treatment of 5xFAD mice reduced brain Aβ40 levels, normalized 4-HNE levels to control levels, improved creatinine clearance, decreased capillary leakage, and lowered S100β plasma levels. NAC improved cognitive performance in 5xFAD mice, as shown by Y-maze. Our findings indicate that Aβ-induced oxidative stress contributes to barrier dysfunction, renal impairment, and cognitive deficits in 5xFAD mice. Notably, NAC treatment mitigates these effects, suggesting its potential as an adjunct therapy for AD and other Aβ-related pathologies by reducing oxidative stress. Full article

Many countries employ mining and ore processing techniques to concentrate and extract precious natural resources. However, the slow leaching of numerous dissolved elements and compounds from large quantities of waste rock and mine tailings can significantly threaten groundwater quality in the affected region. When exposed to oxygen and water, sulfide minerals in mine tailing oxidize, potentially forming acid mine drainage (AMD). Various reclamation techniques can inhibit AMD generation, including monolayer cover combined with an elevated water table (EWT), hydraulic barrier, and cover with capillary barrier effect (CCBE). Selecting the most suitable technique requires consideration of site-specific hydrogeological conditions (e.g., water table depth) and available cover materials. Numerical modeling tools such as PHT3D and MT3D can help identify optimal reclamation methods during preliminary planning stages. The 119-hectare Quémont 2 mine site near Rouyn-Noranda city will undergo reclamation following the closure of its tailings storage facilities (TSF). A three-dimensional numerical groundwater and solute-transport model were constructed and calibrated to simulate the site’s hydrogeological behavior post-closure, enabling selection of the most effective AMD control technique. Subsequently, a three-dimensional multicomponent reactive transport model incorporating various cover designs was developed, with simulations considering climate change impacts. The PHT3D model code, which integrates the PHREEQC geochemical model with the MT3D three-dimensional transport simulator, was employed to evaluate cover performance on the Quémont 2 TSF. Four reclamation configurations were tested: Cell #1 (80 cm single-layer clay cover), Cell #2 (60 cm single-layer clay-sand cover), Cell #3 (60 cm single-layer clay-silt cover), and Cell #4 (120 cm multilayer clay-sand-clay sequence). Simulations were conducted under various climate change scenarios (Representative Concentration Pathways—RCPs 2.6, 4.5, and 8.5). This paper describes the numerical model, cover materials, and modeling results both with and without covers. Results indicate that Cells #1 and #4, completely reduced sulfate in groundwater, suggesting these configurations would provide the most effective reclamation solutions for the Quémont 2 mine site. Full article

Concrete coating technology is a key measure that enhances the durability of concrete structures. This paper systematically studies the performance, applicability, and impact of different types of anti-corrosion coatings on concrete durability, focusing on their resistance to chloride ion penetration, freeze–thaw cycles, carbonation, and sulfate corrosion. The applicability of existing testing methods and standard systems is also evaluated. This study shows that surface-film-forming coatings can create a dense barrier, reducing chloride ion diffusion coefficients by more than 50%, making them suitable for humid and high-chloride environments. Pore-sealing coatings fill capillary pores, improving the concrete’s impermeability and making them ideal for highly corrosive environments. Penetrating hydrophobic coatings form a water-repellent layer, reducing water absorption by over 75%, which is particularly beneficial for coastal and underwater concrete structures. Additionally, composite coating technology is becoming a key approach to addressing multi-environment adaptability challenges. Experimental results have indicated that combining penetrating hydrophobic coatings with surface-film-forming coatings can enhance concrete’s resistance to chloride ion penetration while ensuring weather resistance and wear resistance. However, this study also reveals that there are several challenges in the standardization, engineering application, and long-term performance assessment of coating technology. The lack of globally unified testing standards leads to difficulties in comparing the results obtained from different test methods, affecting the practical application of these coatings in engineering. Moreover, construction quality control and long-term service performance monitoring remain weak points in their use in engineering applications. Some engineering case studies indicate that coating failures are often related to an insufficient coating thickness, improper interface treatment, or lack of maintenance. To further improve the effectiveness and long-term durability of coatings, future research should focus on the following aspects: (1) developing intelligent coating materials with self-healing, high-temperature resistance, and chemical corrosion resistance capabilities; (2) optimizing multilayer composite coating system designs to enhance the synergistic protective capabilities of different coatings; and (3) promoting the creation of global concrete coating testing standards and establishing adaptability testing methods for various environments. This study provides theoretical support for the optimization and standardization of concrete coating technology, contributing to the durability and long-term service safety of infrastructure. Full article