Search Results (1,189)

Ventricular remodeling occurring in heart failure (HF) involves structural disarray of the sarcolemma T-tubule (TT)–sarcoplasmic reticulum (SR) dyad junctions, thereby disrupting the close apposition of L-type Ca²⁺ channels (Ca_V1.2) with ryanodine receptors (RyR2) that trigger SR Ca²⁺ release and myofilament contraction. In a rat ischemic heart failure model expressing low thyroid hormone (TH) function, we used 3D stochastic optical reconstruction microscopy (STORM) to image RyR2 clusters with Ca_V1.2 channels, and the associated protein junctophilin-2 (Jph2). We tested whether treatment with T3, the biologically active form of TH, throughout progression of the disease would preserve T-tubule structure and dyadic ion channel organization. Confocal microscopy of isolated cardiomyocytes (CMs) stained with ANEPPS membrane dye showed significantly decreased TT density in diseased CMs while T3 treatment attenuated TT disorganization. 3D STORM images of dyadic ion channels labeled with fluorescent-tagged antibodies to RyR-Dylight550, Jph-CF647 and Ca_V1.2/IgG-Dylight488 were captured. A density-based algorithm defined RyR2 clusters, and a 400 nm spherical 3D volume of interest around each RyR2 cluster’s centroid determined the number of Ca_V1.2 and Jph2 localizations associated with each RyR2 cluster. Analysis revealed significant reduction in RyR2 cluster size and number with reduced co-localized Jph2 in failing CMs. T3 treatment increased RyR2 cluster numbers and cluster volumes albeit non-significantly, with increased co-clustering of Jph2. The number of Ca_V1.2 co-localized with RyR2 clusters trended lower in the failing CMs. These results support maintaining TH homeostasis in optimizing the nanoscale organization of Ca²⁺ ion channels in triggering Ca²⁺ release and myofibrillar contraction in patients with heart disease. Full article

Precise control of sinter reducibility is essential for stable blast furnace operation. Each mineral phase present in sinter, such as hematite, magnetite and calcium ferrite exhibits different reducibility. In XRD analysis, the requirement for sample pulverization leads to the loss of mineralogical texture information. This makes it difficult to quantitatively correlate the complex mineral phases present in the sinter with reducibility. This study introduces a novel quantitative approach using hyperspectral imaging to distinguish specific mineral morphologies. Reduction experiments simulating blast furnace thermal and gas conditions were conducted on several sinters. Multiple regression analysis was applied to correlate mineral fractions and macroporosity with reduction rates across three distinct reduction stages. In the low-temperature stage, hematite, macroporosity and acicular calcium ferrites were identified as the primary drivers of reduction. In the intermediate stage, acicular calcium ferrites continued to enhance reactivity, whereas coarse calcium ferrite showed a significant negative influence. In the high-temperature stage, macroporosity strongly promoted reduction, while coarse calcium ferrite and magnetite hindered it due to the formation of shell-like metallic iron structures which impede gas diffusion. These findings demonstrate that hyperspectral imaging combined with multi-stage regression analysis offers a useful tool for designing optimal sinter mineralogy for blast furnace performance. Full article

Orthodontic pain, a fundamental biological response to mechanically induced tooth movement, is primarily associated with sterile inflammation and neurogenic processes within the periodontal ligament (PDL). Although photobiomodulation therapy (PBMT) has been widely investigated as a nonpharmacological approach for pain attenuation, its mechanisms of action remain incompletely understood, and current interpretations are often limited to peripheral anti-inflammatory effects. This review re-examines the biological basis of orthodontic pain by integrating evidence derived predominantly from in vitro and in vivo experimental studies. Particular emphasis is placed on neurogenic inflammation, neuropeptide regulation, and neuron–glia interactions along the trigeminal nociceptive pathway. PBMT can reduce periodontal inflammatory/neuropeptide-related markers and pain-related behaviors in selected models; however, evidence for direct central neuron–glia modulation remains largely marker-based and parameter-dependent. Direct functional validation of trigeminal circuit modulation (e.g., electrophysiological recordings or calcium imaging) remains limited in orthodontic pain models; thus, the proposed neuroimmune mechanisms should be interpreted as testable hypotheses for future work. By synthesizing mechanistic insights across multiple biological levels, this review proposes a broader framework for understanding PBMT-mediated pain modulation extending beyond conventional peripheral models. These perspectives may help clarify inconsistencies in the reported outcomes and provide a rationale for future hypothesis-driven experimental and translational research. Full article

Background: Uncontrolled hemorrhage, especially at non-compressible sites, remains a major cause of preventable trauma deaths. This study reports the development of fibrinogen-loaded calcium carbonate (CaCO₃) microparticles that combine hemostatic activity with self-propelling capability for targeted delivery against blood flow, with a focus on understanding formulation-dependent trade-offs among particle yield, protein loading, clotting performance, and transport behavior. Methods: Microparticles were synthesized via a precipitation method using different carbonate sources and characterized for yield, morphology, size, and fibrinogen encapsulation. Hemostatic function was assessed using rotational thromboelastometry (ROTEM) in fibrinogen-deficient plasma. Propulsion behavior was evaluated following exposure to protonated tranexamic acid (TXA⁺), which triggers CO₂ generation. Particle size and encapsulation were examined by microscopy and fluorescence imaging. Results: The precipitation method produced spherical micrometer-sized particles, with fibrinogen inclusion reducing yield and particle size relative to unload controls. Fluorescence microscopy confirmed successful encapsulation. Encapsulation efficiency varied with formulation, with sodium carbonate-based particles showing higher relative fibrinogen loading. ROTEM analysis demonstrated that fibrinogen-loaded particles significantly improved clot formation, increasing maximum clot firmness compared to fibrinogen-free particles, although performance remained formulation-dependent. TXA⁺-triggered propulsion achieved maximum speeds up to 4.221 cm/s. Fibrinogen-loaded particles exhibited longer activation lag times than unloaded particles, indicating a trade-off between hemostatic functionality and propulsion kinetics. Conclusions: Fibrinogen-loaded CaCO₃ microparticles exhibit both hemostatic activity and chemically triggered motion in vitro. The study identifies key formulation-dependent trade-offs between particle yield, fibrinogen loading, clotting performance, and propulsion behavior. While these findings support the feasibility of combining localization and clot stabilization mechanisms, further studies under physiologically relevant flow conditions and in vivo models are required to evaluate their potential for active delivery in non-compressible hemorrhage. Full article

Carbonyl stress, chronic inflammation, and progressive tissue injury accompany type 2 diabetes mellitus (T2DM) and obesity. Yet, the molecular systems that connect these processes with cardiac, vascular and neuronal complications are incompletely defined. This review examines the AGE–RAGE–DIAPH1 axis as a mechanistic link between metabolic dysfunction and diabetic myocardial and neuronal injury, with emphasis on vascular and myocardial remodeling and emerging implications for autonomic neuronal vulnerability. We summarize current evidence on the formation and accumulation of advanced glycation end-products and other RAGE ligands in metabolic disease, DIAPH1’s structural and signaling role as an intracellular effector of RAGE, and the cellular consequences of pathway activation in vascular, neural, and cardiac tissues. Across experimental models, this signaling axis promotes oxidative stress and inflammatory activation, leading to endothelial dysfunction and barrier failure. Subsequent fibrotic remodeling provides a biologically plausible route through which metabolic stress may be translated into persistent organ injury. In the heart, these mechanisms are linked to coronary microvascular dysfunction, altered cardiomyocyte phenotype, calcium handling abnormalities, and myocardial fibrosis. In the autonomic nervous system, limited but emerging data connect RAGE activation to oxidative injury and mitochondrial dysfunction, abnormal neuronal excitability, and structural vulnerability. Direct evidence linking DIAPH1 to autonomic neurons is lacking. We also review biomarker candidates related to this pathway, including circulating AGEs and soluble RAGE isoforms, skin AGE measurements, imaging markers of myocardial remodeling, and autonomic functional measures. Finally, we discuss pharmacological and natural compounds that target AGE formation, ligand accumulation, RAGE signaling, or intracellular protein interactions linked to this axis. Overall, the available evidence supports the AGE–RAGE–DIAPH1 axis as a credible mechanistic concept and a potentially informative translational hypothesis in T2DM. However, the AGE–RAGE component is supported more strongly than DIAPH1-specific involvement in human diabetic myocardial disorder or cardiovascular autonomic neuropathy. The value of DIAPH1 as a biomarker or therapeutic target in these neurocardiac complications remains to be established. Full article

Background: Pregnancy-related transient osteoporosis of the hip (PR-TOH) is an uncommon and frequently underdiagnosed condition that typically presents with acute hip pain during late pregnancy or the early postpartum period. Because its clinical presentation is nonspecific and overlaps with pregnancy-related pelvic girdle pain, the diagnosis is often delayed, and the initial management is suboptimal. Although bilateral involvement has been reported, comparative data on diagnostic work-up, multidisciplinary management, and follow-up remain limited. Case Presentation: We report a case of bilateral PR-TOH in a 35-year-old Caucasian primigravida (G1, P0) who presented at 31 + 6 weeks of gestation with progressively worsening bilateral hip pain that culminated in severe functional impairment and wheelchair dependence. Initial ultrasound, laboratory work-up, and rheumatological screening were inconclusive, and intra-articular corticosteroid injections failed to relieve symptoms and were temporally associated with deterioration of glycaemic control and a periorbital and palmar eczematous rash. Magnetic resonance imaging (MRI) demonstrated diffuse bone marrow oedema in both femoral heads with preserved articular cartilage and no evidence of avascular necrosis, supporting a diagnosis of bilateral PR-TOH. Postpartum dual-energy X-ray absorptiometry (DXA) confirmed reduced bone mineral density at both femoral necks (Z-scores below −2.0). Pregnancy was prolonged until 37 + 4 weeks, and delivery was by elective caesarean section. Postpartum care included analgesia, calcium and vitamin D supplementation, structured physiotherapy, and a graded weight-bearing rehabilitation programme. Bone mineral density improved markedly on follow-up DXA at six months, with complete clinical recovery and no further imaging abnormalities at 12, 24, and 30 months. Conclusions: PR-TOH should be considered in pregnant or postpartum women with persistent hip pain and progressive functional limitation. MRI is the key imaging modality for early diagnosis and for excluding alternative causes, whereas DXA remains the reference standard for quantifying bone mineral density and monitoring recovery. Bilateral presentations require a multidisciplinary, individualised approach that addresses both maternal and obstetric outcomes. Full article

Genetically encoded voltage indicators (GEVIs) have long promised optical access to membrane potential, yet their adoption has lagged significantly behind genetically encoded calcium indicators. A central but underappreciated reason is that the metrics used to evaluate and compare GEVIs—fractional fluorescence change (ΔF/F), kinetics, and signal-to-noise ratio—rest on an assumption that is frequently violated: that GEVI fluorescence reflects a single underlying process. In this perspective, we argue that GEVI signals are composite optical measurements, arising from the superposition of voltage-dependent fluorescence, intracellular and nonresponsive signal, background, and contributions from neighboring cells. Under these conditions, ΔF/F is not a measure of sensor sensitivity but a contrast metric whose value depends on baseline fluorescence composition, optical sampling, and imaging configuration. This reinterpretation has two key consequences. First, it explains a substantial source of variability in GEVI performance that is currently attributed to noise or experimental inconsistency. Second, and more importantly, it reveals that the complexity of GEVI signals is not a limitation to be minimized but a resource to be exploited. By resolving composite signal components, GEVIs can report multiplexed physiological variables, expose hidden conformational states of voltage-sensing domains, probe membrane organization, and reveal intracellular and intercellular electrical coupling. We propose that realizing the full potential of GEVIs requires treating ΔF/F not as a gold standard for sensor performance, but as one interpretable component of a richer optical measurement whose structure encodes multiple layers of cellular physiology. Full article

Coronary artery calcification (CAC) represents a clear sign of advanced atherosclerosis and a strong indicator of coronary artery disease burden and cardiovascular risk. Beyond its established prognostic value, CAC significantly influences plaque biology, lesion morphology, and the technical complexity of percutaneous coronary intervention (PCI). This review summarizes current knowledge on the mechanisms of vascular calcification, its clinical determinants, diagnostic assessment, and therapeutic implications. Vascular calcification is now understood as an active, regulated process involving osteogenic transdifferentiation of vascular smooth muscle cells, inflammatory signaling pathways, extracellular vesicle release, and disturbances in mineral metabolism. Distinct calcification phenotypes exert different effects on plaque stability: micro- and spotty calcifications are frequently linked to plaque vulnerability, whereas dense, sheet-like calcification is more typical of stable fibrocalcific lesions. The prevalence of CAC increases with age and differs between sexes, while cardiometabolic risk factors, chronic kidney disease, systemic inflammation, and genetic predisposition further contribute to its development. Noninvasive computed tomography remains the cornerstone for CAC detection and quantification, enabling reliable cardiovascular risk stratification. Intravascular imaging techniques, particularly intravascular ultrasound and optical coherence tomography, provide detailed characterization of calcified plaque morphology and support optimal procedural planning. In patients with heavily calcified lesions, intravascular imaging-guided lesion preparation and stent optimization represent the most effective strategy for improving PCI outcomes. Full article

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by fibroblast growth factor 23 (FGF-23)-secreting tumors, typically of mesenchymal origin, leading to renal phosphate wasting and severe bone demineralization and fragility fractures. Diagnosing TIO remains a significant clinical challenge, particularly when coexisting mineral metabolism disorders, such as hypercalcemic hyperparathyroidism, are masking its clinical presentation. Case Presentation: A 74-year-old woman with fragility fractures, generalized bone pain, and nephrolithiasis was initially diagnosed with primary hyperparathyroidism due to concomitant hypercalcemia, hypophosphatemia, and elevated parathyroid hormone (PTH). Despite a successful parathyroidectomy, which normalized calcium levels, severe hypophosphatemia persisted due to renal phosphate wasting. High FGF-23 levels and subsequent functional imaging indicating a somatostatin receptor-positive lesion in the left popliteal fossa led to the diagnosis of TIO. Surgical resection immediately normalized FGF-23 levels, leading to a slower rise in phosphorus during follow-up. Histopathology revealed a tophaceous-like giant cell granulomatous reaction, recalling the earlier report by Prader. Conclusions: This case highlights that parathyroid disorders can coexist with TIO, and they may delay its diagnosis. In this circumstance, a high index of clinical suspicion is represented by the persistence of hypophosphatemia post-parathyroidectomy. Full article

Low-lime calcium silicate cement develops strength mainly through carbonation curing. However, long curing times can limit precast productivity. This study examined whether recycled coarse aggregates promote carbonation in CSC concrete via porous adhered mortar, which facilitates CO₂ transport. Two mixes (CSC replacement 50%, W/B 0.45) were prepared: NCA-CSC50 and RCA-CSC50 (100% NCA replacement). After steam curing, the specimens were carbonated in 20% CO₂ at 20 °C and 60% RH for 1–14 days. The carbonation degree was quantified from phenolphthalein-sprayed cross-sections by image binarization, and depth-dependent phase evolution and ITZ changes were assessed by XRD and SEM–EDS. RCA-CSC50 exhibited a higher carbonation degree and coefficient and achieved higher compressive strength, exceeding those of NCA-CSC50 after 3 days. XRD analysis performed after 14 days of carbonation curing revealed that portlandite peaks remained in NCA-CSC50 at depths of 35–50 mm, whereas they were not detected at the same depths in RCA-CSC50, indicating more extensive carbonation penetration in the RCA-containing mixture. This result is consistent with the quantitatively higher carbonation degree and carbonation coefficient of RCA-CSC50 compared with NCA-CSC50. SEM–EDS observations further revealed multiple ITZs around the recycled aggregate. Although the ITZs were not directly quantified as CO₂ diffusion paths, their presence is likely associated with the enhanced carbonation observed in RCA-CSC50 by providing additional connected zones for CO₂ ingress. These findings suggest that RCA can be considered not only as a recycled aggregate source but also as a potential means of facilitating CO₂ transport in carbonation-cured CSC concrete. Furthermore, the combined use of carbonation-reactive binders and recycled aggregates is expected to contribute to the broader application of low-carbon concrete technologies by reducing construction waste and expanding the implementation of CCUS-based approaches. Full article

Background: Interventional cardiology is increasingly being reshaped by rapid progress in non-invasive cardiovascular imaging. Coronary computed tomography angiography (CTCA), once used mainly to exclude obstructive coronary artery disease (CAD), is now being adopted as a broader planning instrument before percutaneous coronary intervention (PCI). Its ability to generate high-resolution three-dimensional visualization of the coronary tree, together with functional assessment through CT-derived fractional flow reserve (FFR-CT) and more advanced plaque analysis supported by artificial intelligence (AI), has expanded its relevance from diagnosis alone to strategic procedural preparation. In this setting, CTCA can help refine lesion assessment, anticipate technical complexity, and support better procedural and clinical outcomes. Technological Advancements: The value of CTCA for both diagnosis and risk stratification has increased substantially with recent technical innovation. Among the most important developments is the maturation of FFR-CT, which enables non-invasive physiological interrogation of coronary stenoses using computational modeling. At the same time, artificial intelligence and deep learning tools are reshaping the CTCA workflow by improving automation, facilitating plaque analysis, and highlighting adverse plaque characteristics such as positive remodeling, spotty calcification, and the napkin-ring sign. Clinical Applications: In modern catheterization practice, CTCA is increasingly used to address anatomically demanding scenarios. Its role is particularly valuable in chronic total occlusion (CTO) intervention, where it can delineate occlusion length, stump characteristics, vessel course, and collateral anatomy before the procedure. Its usefulness also extends beyond CTO PCI by supporting vessel sizing, stent planning, and anticipation of lesion preparation requirements in complex coronary disease. Challenges: Despite these advantages, several barriers continue to limit wider implementation, including blooming from heavy calcification, radiation burden, contrast-related renal concerns, and the practical difficulty of embedding CTCA-based planning into routine workflows. Conclusions: CTCA is becoming an increasingly important adjunct in PCI planning because it can combine anatomical definition, physiological interpretation, and plaque-level information before invasive treatment is undertaken. Overall, this review emphasizes CTCA not only as a diagnostic modality, but also as a practical pre-procedural roadmap that can guide lesion selection, stent planning, calcium modification strategies, and overall PCI strategy. Full article

A substantial proportion of cardiovascular (CV) events occurs in individuals without previously diagnosed CV disease, underscoring the need for improved primary prevention strategies. Traditional risk scores provide probabilistic estimates but fail to directly identify the presence and heterogeneity of subclinical atherosclerosis. This review summarizes current evidence on advanced multimodality imaging approaches for identifying high-risk individuals without prior CV events. Evidence from cohort studies, randomized trials, and meta-analyses was examined to evaluate the role of coronary artery calcium (CAC) scoring, coronary computed tomography angiography (CCTA), perivascular fat attenuation index (FAI), and vascular ultrasound in risk stratification. CAC scoring remains the most validated and widely recommended tool, offering robust prognostic value and significant risk reclassification, particularly in intermediate-risk individuals. CCTA provides additional insights into plaque burden and high-risk phenotypes, while FAI enables noninvasive assessment of coronary inflammation, improving risk prediction beyond anatomical measures. Vascular ultrasound offers a radiation-free, accessible method for detecting systemic plaque burden and refining risk estimation. Overall, multimodality imaging enhances the identification of subclinical disease and supports more individualized, disease-based risk assessment. Future research should clarify cost effectiveness, optimize patient selection, and determine whether imaging-guided strategies improve long-term clinical outcomes. Full article

The gelation property is one of the core functional characteristics of konjac glucomannan (KGM). KGM mainly forms gels through ionic crosslinking, deacetylation and compounding with other colloids. Exploring novel gelation technologies for the precise regulation of KGM gel properties is the research focus in this field. In this work, an alternating current (AC) electric field was applied to trigger KGM gelation in the presence of calcium chloride (CaCl₂). The structure and viscoelastic properties (including storage modulus G′, loss modulus G″ and loss factor tanδ) of the gels were analyzed by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy (RS), scanning electron microscopy (SEM), X-ray diffraction (XRD), simultaneous differential scanning calorimetry/thermo-gravimetric analyzer (DSC/TGA) and rheometer. FTIR and RS revealed that KGM underwent partial degradation and deacetylation under the AC electric field. Calcium ions and chloride ions dissociated from CaCl₂ are adsorbed onto the hydroxyl groups of KGM molecules. KGM molecules constituting the gels still retain partial original acetyl groups. SEM images showed that the gels had a porous structure with a coarse surface. XRD patterns showed the gels contained complex CaCl₂ hydrates. Simultaneous DSC/TGA analysis indicated that the gel with excellent thermal stability exhibited distinct melting endothermic peaks corresponding to CaCl₂ hydrates. Rheological data showed that, apart from KGM concentration, G′ and G″ of the gels gradually increased with the elevation of CaCl₂ concentration, applied voltage and electric treatment duration. However, when CaCl₂ concentrations, voltage, and electric treatment time exceeded their respective critical values, both started to decrease. Taking G′ as the evaluation index, the optimal preparation conditions for KGM-CaCl₂ electrogel were determined as follows: KGM 0.5%, CaCl₂ 1.2%, electric treatment duration 45 min, and voltage 24 V. Full article

Background/Objectives: Insomnia severely impairs quality of life. Oral melatonin (MEL) suffers from poor brain delivery. Intranasal administration bypasses the blood–brain barrier, but rapid mucociliary clearance shortens drug retention, and MEL poor water solubility limits its nasal dissolution. Traditional in situ gels have “gelation-first, spreading-second” defects, causing uneven distribution. Herein, we developed a two-step sequential ion-triggered in situ gel combined with MEL liposomes (MEL-Lips-Gel) to enhance solubility, achieve instant uniform coating, and prolong retention for efficient nose-to-brain delivery. Methods: MEL-Lips were dispersed in alginate (first component) and calcium gluconate served as the second component. After sequential spray, the two components mix and form an ion-crosslinked gel. Rheology, in vivo fluorescence imaging, in vitro release, open-field/sucrose preference tests, and H&E staining were performed. Results: MEL-Lips showed uniform size and good encapsulation. The sequential system achieved instant widespread spreading and rapid gelation, significantly prolonged nasal retention, enabled sustained brain delivery, and reversed insomnia-induced hyperactivity and anxiety-like behaviors more effectively than oral MEL, intranasal MEL solution, liposomes alone, or non-liposomal gel, with good nasal safety. Conclusions: This sequential ion-triggered liposome-in-gel strategy synergistically overcomes rapid clearance (via gel) and poor solubility (via liposomes), enhancing nose-to-brain delivery of melatonin and providing a promising platform for insomnia therapy. Full article

Background: Osteoporosis, a chronic disease with a major epidemiologic impact amid menopause might be aggravated by co-ailments such as adrenal tumours, with an increasing incidence due to a larger access to imaging evaluation. The objective was to evaluate bone profile in relationship with adrenal profile in non-functioning adrenal tumours (NFATs), based on menopausal DXA categories (osteoporosis, osteopenia and normal). Methods: A retrospective real-life study was conducted amid a cross-sectional analysis in anti-osteoporotic drugs naïve subjects. Adrenal profile included baseline morning plasma cortisol (base-cortisol), second-day cortisol (DST-cortisol) after 1 mg dexamethasone testing, ACTH, and largest tumour diameter at CT (D-CT). Results: Ninety-five patients (mean age 61.59 ± 7.83 years) had 24.21% osteoporosis, 47.37% osteopenia, and 28.42%—normal DXA. Base-cortisol, DST-cortisol, ACTH and D-CT were similar between the groups. Total serum calcium was lower in osteoporosis versus osteopenia, versus normal DXA (9.26 ± 0.52 versus 9.61 ± 0.41 mg/dL, p = 0.005, respectively, 9.79 ± 0.47 mg/dL, p < 0.001). Osteocalcin, respectively, CrossLaps were elevated in osteoporosis versus osteopenia. MACS prevalence was 27.37% (no between-group difference). Osteoporosis group: CrossLaps correlated with DST-cortisol (r = −0.550, p = 0.019). Multiple linear regression model to predict lumbar BMD explained 47.1% of the variance in lumbar BMD (R² = 0.471). ACTH was an independent variable for lumbar BMD (p = 0.007). BMI represented the main influential contributor to this model having the highest β of 0.490, and it also explained 49.1% (R² = 0.491) of total hip BMD variation. Conclusions: This study emphasises a heterogeneous connection between adrenal profile in NFATs and clinical evaluation of the bone status. More comprehensive prospective studies are mandatory to assess this multifactorial bone–adrenal interplay in order to improve the overall management. Full article