Search Results (877)

Background: Several cohort studies have demonstrated a link between subclinical carotid atherosclerosis and obstructive chronic airflow limitation. These conditions exhibit common risk factors associated with unhealthy lifestyles, as well as analogous pathophysiological mechanisms, including chronic low-degree systemic inflammation. Purpose: The aim of this study was to investigate the association between airflow obstruction and carotid intima–media thickness (c-IMT), together with the influence of inflammatory biomarkers on this relationship, in patients diagnosed with chronic obstructive pulmonary disease (COPD). Methods and Patients: This study is cross-sectional and includes 106 patients with stable COPD. All patients underwent evaluation through spirometry, carotid ultrasound, and assessment of inflammatory biomarkers, including C-reactive protein, fibrinogen, and erythrocyte sedimentation rate. The relationship between carotid subclinical atherosclerosis and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage of COPD was assessed. Additionally, we compared patients with two positive biomarkers of inflammation with those who had no positive inflammatory biomarkers. Results: Significant statistical differences were observed in carotid intima–media thickness values associated with the severity of airflow obstruction, with measurements of 1.03 mm in COPD stage 1–2 GOLD, 1.07 mm in COPD GOLD 3, and 0.96 mm in GOLD 4 (p = 0.04). However, no direct correlation with forced expiratory volume in the first second (FEV1) was identified. The post hoc analysis revealed a notable increase in carotid wall thickness for the early stages of COPD. C-IMT demonstrated a significant association with inflammation parameters, muscle dysfunction, body composition, and lipid profile. The comparison of groups exhibiting two positive inflammatory biomarkers with those with no positive inflammatory markers revealed significant differences in age, c-IMT, exercise tolerance, and COPD symptoms. Conclusions: Subclinical carotid atherosclerosis is evident from the early stages of obstructive airflow limitation. Carotid intima–media thickness is significantly higher in patients with positive inflammatory biomarkers. Full article

Objective: This study aimed to evaluate blood count-derived inflammatory indices—the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammation index (SII)—in patients with fibromyalgia and to explore their association with disease activity and pain severity. Methods: A cross-sectional study was conducted with 85 fibromyalgia patients and 84 age- and sex-matched healthy controls. Demographic, clinical, and laboratory data were recorded. Inflammatory indices were calculated from blood counts. Disease activity and functional status were assessed with the Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), and pain severity with the Visual Analog Scale (VAS). Results: Compared to controls, the fibromyalgia group had significantly higher BMI, PLR, MLR, and NLR (all p < 0.05), and lower lymphocyte levels. PLR and MLR moderately discriminated fibromyalgia (AUC = 0.623 and 0.661, respectively), suggesting limited diagnostic utility when used alone. MLR and BMI were independently associated with fibromyalgia in multivariate analysis. Disease duration showed significant positive correlations with PLR (r = 0.167), MLR (r = 0.228), FIQ (r = 0.773), HAQ (r = 0.589), and VAS at rest and movement (r = 0.584 and r = 0.601; all p < 0.05). PLR, MLR, and NLR were also positively correlated with VAS scores, while SII showed no significant associations. FIQ was strongly correlated with pain severity and HAQ with VAS during movement. Conclusions: Blood count-derived indices, particularly PLR and MLR, are elevated in fibromyalgia and are associated with disease duration, severity, and pain. Although PLR and MLR were higher in fibromyalgia patients, their discriminatory ability was limited and should be interpreted cautiously, indicating that their diagnostic specificity is low, as these ratios primarily reflect nonspecific inflammatory processes. Full article

Fibromyalgia Syndrome (FMS) is a chronic syndrome commonly characterized by widespread musculoskeletal pain and fatigue. Current evidence suggests that FMS diagnosis relies on clinical evaluation and patient-reported symptoms. MicroRNAs, which serve as key regulators of gene expression, have been proposed to play a role in the pathogenesis of FMS and other chronic pain syndromes. In this pilot study, miRNA-223-3p expression levels were examined in patients with FMS, and their relationship with pain intensity—assessed using the Visual Analog Scale (VAS)was evaluated. To obtain a broader understanding of the inflammatory response, serum interleukin-1 beta (IL-1β) levels were also measured. miRNA-223-3p expression levels were significantly reduced in the FMS group compared with healthy controls (p < 0.05), whereas IL-1β levels did not differ significantly between the groups (p = 0.1135). The negative correlation between miRNA-223-3p and VAS scores indicates that lower miRNA levels are associated with increased pain severity. Overall, these results suggest that reduced miRNA-223-3p expression levels may be linked to neuroimmune processes and heightened pain perception in FMS. The findings provide valuable preliminary insights that may guide future studies with larger sample sizes. Full article

Background and Objectives: The aim of this study was to evaluate the relationship between low back pain questionnaires and radiological stenosis severity in patients with lumbar spinal stenosis (LSS). Materials and Methods: Patients aged 50 years and over who presented with complaints of low back pain and were diagnosed or not diagnosed with LSS by magnetic resonance imaging (MRI) were included in the study. Demographic data, physical examination findings, and walking distance were recorded. Pain severity was assessed using the Visual Analog Scale (VAS), and patients completed the Oswestry Disability Index (ODI), the Istanbul Low Back Pain Disability Index (ILBPDI), and the Swiss Spinal Stenosis Questionnaire (SSS-Q). Results: A total of 120 patients with LSS (n = 56) and without LSS (n = 64) were included in the study. No significant differences were found between the groups in terms of demographic variables (p > 0.05). Neurogenic claudication and lumbar extension limitation were higher in the LSS group (p = 0.033 and p = 0.008, respectively), and walking distance was significantly shorter compared to the group without LSS (p = 0.024). There were significant differences between the VAS, ODI, ILBPDI, and SSS-Q scores between the two groups (p < 0.05). A strong positive correlation exists between the radiological severity of LSS and SSS-Q (p < 0.001, r = 0.707). Additionally, ROC analysis revealed that the SSS-Q had a significantly higher diagnostic value for LSS compared to the ODI and ILBPDI (p < 0.001). For the SSS-Q, likelihood ratios indicated limited diagnostic relevance (PLR 4.04 [95% CI: 2.45–6.67]; NLR 0.22 [95% CI: 0.13–0.44]). Conclusions: SSS-Q, ODI, and ILBPDI scores vary significantly between patients with and without LSS. Although the SSS-Q correlates most strongly with radiological LSS severity, its diagnostic utility appeared of minor importance, as likelihood ratios indicated limited discriminative ability. Full article

Hyaluronidase and its modified analogs are clinically significant enzyme-based pharmaceuticals used to treat fibrosis, increase tissue permeability, and improve drug diffusion. While pharmacopeial quality control methods are well defined, scientific literature provides limited information about the physicochemical evaluation of such enzyme pharmaceuticals, necessitating a more holistic analytical approach. Commercial pharmaceuticals of hyaluronidase and its modified analog were analyzed using a combination of dynamic light scattering, infrared spectroscopy, and detection of intrinsic radiothermal emission (RTE). Dimensional characteristics were studied using a Zetasizer Nano ZSP (ZetasizerNano ZSP, Malvern Instruments, Malvern, UK) confirmed theoretical diameters of 5–8 nm, consistent with experimental values (6–8 nm). Fourier-Transform infrared spectroscopy (FTIR) (Agilent Cary 630, Agilent Technologies, Santa Clara, CA, USA) revealed characteristic transmission bands for the modified enzyme at 1464, 1448, 1326, 1158, and 1010 cm⁻¹, confirming structural modification. RTE measurements using a TES-92 detector (TES Electrical Electronic Corp., Taipei, Taiwan) demonstrated a correlation between emission intensity and shelf life: 12.8 ± 0.8 µW/m² for proper shelf-life samples, 8.3 ± 0.8 µW/m² for six-month-expired, and 5.1 ± 1.0 µW/m² for one-year-expired pharmaceuticals. The study offers a promising supplementary tool for pharmaceutical quality control of hyaluronidase-based drugs. Full article

Deep coalbed methane (CBM) development faces significant challenges due to extreme geological conditions (high stress, elevated pressure, high temperature) that differ fundamentally from shallow reservoirs. Traditional productivity models developed for shallow CBM often fail to accurately predict deep reservoir performance. The complex “stress-desorption-flow” multi-field coupling mechanism, intensified under deep conditions, critically controls production dynamics but remains poorly understood. This study develops a multi-layer, commingled, coupled geomechanical-flow model for the Hujiertai deep CBM block (2140~2170 m) in Xinjiang, China. The model, integrating gas-water two-phase flow, Langmuir adsorption, and transient geostress evolution, was validated against field production data, achieving a low relative error of 1.2% in the simulated average daily gas rate. Results indicate that: (1) Geomechanical coupling is critical. The dynamic competition between effective stress compaction and matrix shrinkage limits fracture porosity reduction to ~2%, enabling a characteristic “rapid incline, 1–2-year plateau, gradual decline” production profile and significantly enhancing cumulative gas production. (2) Porosity (10~30%) is positively correlated with productivity: a 10-percentage-point increase raises the peak gas rate by 2.1% and cumulative production by 2.8%. Conversely, high initial cleat permeability boosts early rates but accelerates geomechanical damage (cleat closure), lowering long-term productivity. (3) Stimulation parameters show a trade-off. SRV only dictates short-term, near-wellbore production. Higher fracture permeability (peak rate +17% per 500 mD) boosts early output but accelerates depletion and stress-induced closure. The multi-field coupling mechanisms revealed and the robust model developed provide a theoretical basis for optimizing fracturing design and production strategies for analogous deep CBM plays. Full article

Background/Objectives: Hemiplegic shoulder pain (HSP) is a frequent post-stroke complication affecting 30–65% of survivors, contributing to motor dysfunction and reduced quality of life. Balance impairment is another major concern that increases fall risk. This study aimed to examine the associations between HSP, shoulder range-of-motion (ROM) limitations and balance performance using both clinical and sensor-based evaluations. Methods: In this cross-sectional study, 108 stroke survivors (54 with HSP, 54 without) were assessed. Pain intensity was evaluated using the Visual Analog Scale (VAS), balance with the Berg Balance Scale (BBS), and shoulder mobility and postural sway with the validated Euleria Lab IMU-based system integrated with a force platform. Between-group differences were analyzed using the Mann–Whitney U test, and correlations between pain, ROM, balance, and fall-risk indices were determined via Spearman coefficients. Results: Participants with HSP had significantly lower BBS scores (20.96 ± 8.71) than those without HSP (34.58 ± 11.71; p < 0.001). VAS activity scores were negatively correlated with BBS (r = −0.196, p = 0.043) and positively correlated with postural sway and fall-risk parameters, particularly under eyes-closed conditions. Shoulder ROM limitations were linked to poorer balance, and both static and dynamic fall-risk indices were strongly correlated with pain severity (r = 0.676 and r = 0.657; p < 0.001). Conclusions: HSP was associated with impaired balance and elevated fall risk in stroke survivors. The combination of clinical scales and wearable sensor-based measurements provides a comprehensive understanding of postural control deficits. These findings emphasize the need for rehabilitation strategies targeting pain reduction, shoulder mobility, and balance to support functional recovery. Full article

Background/Objectives: Acute stress is known to influence food-related motivation and decision-making, often promoting a preference for energy-dense, palatable foods. However, traditional laboratory paradigms have limited ecological validity. This study examined the relationship between stress-induced physiological changes, eating behavior traits, and food cravings using a virtual reality (VR) adaptation of the Trier Social Stress Test (VR-TSST) followed by a VR supermarket task in adolescents. Methods: Thirty-eight adolescents (mean age 15.8 ± 0.6 years) participated in the study. Physiological parameters (HR, QT, PQ intervals) were recorded pre- and post-stress using a portable ECG device (WIWE). Perceived stress and eating behavior traits were evaluated with the Perceived Stress Scale (PSS) and the Three-Factor Eating Questionnaire (TFEQ-R21C), respectively. Immediately after the VR-TSST, participants performed a VR supermarket task in which they rated cravings for sweet, fatty, and healthy foods using visual analog scales (VAS). Paired-samples t-tests examined pre–post changes in physiological parameters, partial correlations explored associations between ECG responses and eating traits, and a 2 × 3 mixed-model Repeated Measures ANOVA assessed the effects of food type (sweet, fatty, healthy) and uncontrolled eating (UE) group (low vs. high) on post-stress cravings. Results: Acute stress induced significant increases in HR and QTc intervals (p < 0.01), confirming a robust physiological stress response. The ANOVA revealed a strong main effect of food type (F(1.93, 435.41) = 168.98, p < 0.001, η²p = 0.43), indicating that stress-induced cravings differed across food categories, with sweet foods rated highest. A significant food type × UE group interaction (F(1.93, 435.41) = 16.49, p < 0.001, η²p = 0.07) showed that adolescents with high UE exhibited greater cravings for sweet and fatty foods than those with low UE. Overall, craving levels did not differ significantly between groups. Conclusions: The findings demonstrate that acute stress selectively enhances cravings for high-reward foods, and that this effect is modulated by baseline uncontrolled eating tendencies. The combined use of VR-based stress induction and VR supermarket simulation offers an innovative, ecologically valid framework for studying stress-related eating behavior in adolescents, with potential implications for personalized nutrition and the prevention of stress-induced overeating. Full article

Background: Recent research suggests that damage to right hemisphere regions homotopic to the left hemisphere language network affects language abilities to a greater extent than previously thought. However, few studies have investigated acute disruption of language after lesion to the right hemisphere. Here, we examined lesion correlates of acute speech deficits following left and right hemisphere ischemic stroke to clarify the neural architecture underlying early language dysfunction. Methods: We retrospectively analyzed 410 patients (225 left, 185 right hemisphere lesions) from the Stroke Outcome Optimization Project dataset. Presence and severity of speech deficits was measured using the National Institute of Health Stroke Scale Best Language subscore within 48 h of onset. Manual lesion masks were derived from clinical MRI scans and normalized to MNI space. Lesion-symptom mapping was conducted using voxelwise and region-of-interest analyses with permutation correction (5000 iterations; p < 0.05), controlling for total lesion volume. Results: Speech deficits were observed in 53.7% of the cohort (58.2% left, 48.1% right hemisphere lesions). In the full sample, the presence of speech deficits was associated with bilateral subcortical and perisylvian damage, including the external and internal capsules, insula, putamen, and superior fronto-occipital fasciculus. Severity of speech deficits localized predominantly to left hemisphere structures, with peak associations in the external capsule (Z = 6.39), posterior insula (Z = 5.64), and inferior fronto-occipital fasciculus (Z = 5.43). In the right hemisphere cohort, the presence and severity of speech deficits were linked to homologous regions, including the posterior insula (Z = 3.70) and external capsule (Z = 3.63), although with smaller effect sizes relative to the left hemisphere cohort. Right hemisphere lesions resulted in milder deficits despite larger lesion volumes compared with left hemisphere lesions. Conclusions: Acute speech impairment following right hemisphere stroke is associated with damage to a homotopic network encompassing perisylvian cortical and subcortical regions analogous to the dominant left hemisphere language network. These findings demonstrate that damage to the right hemisphere consistently results in acute speech deficits, challenging the traditional left-centric view of post-stroke speech impairment. These results have important implications for models of bilateral language representation and the neuroplastic mechanisms supporting language recovery. Full article

Background/Objectives: Chronic pruritus is a common and distressing symptom in geriatric dermatology, often intensified by age-related changes and frailty. Frailty, reflecting physiological decline and reduced resilience, may increase itch perception, yet its link to pruritus severity remains unclear. Our study aims to evaluate the association between pruritus severity and frailty in older dermatology patients and identify related clinical and dermatologic factors. Methods: A total of 171 patients aged ≥65 years with pruritus lasting more than six weeks were included. Pruritus was measured using the Visual Analog Scale (VAS) and 5-D Itch Scale, while frailty was assessed by the FRAIL scale. Xerosis severity was rated by the Overall Dryness Score (ODS), and data on itch duration, comorbidities, and medications were analyzed. Statistical significance was defined as p < 0.05. Results: The mean VAS and 5-D Itch scores were 6.2 ± 2.6 and 12.5 ± 3.1. Itch severity increased significantly across frailty categories (p < 0.001). Strong correlations were found between VAS and itch duration (r = 0.79, p < 0.001), ODS (r = 0.66, p < 0.001), and medication count (r = 0.56, p < 0.001). Similar associations were seen for 5-D Itch (r = 0.61, 0.64, and 0.54; p < 0.001). Age and comorbidities showed no significant correlation (p > 0.05). Conclusions: Pruritus severity in older adults was associated with xerosis, frailty, and polypharmacy, while no significant association with age was observed in univariable analyses. Incorporating frailty screening, ODS evaluation, and geriatric consultation into dermatologic care may improve management and quality of life in older adults with chronic pruritus. These findings reflect associations rather than causal relationships, as the cross-sectional design does not permit inference of directionality. Full article

The replacement of ionizable functional groups that are predominantly charged at physiological pH with neutral bioisosteres is a common strategy in medicinal chemistry; however, its impact on binding affinity is often context-dependent. Here, we investigated a series of amide derivatives of a glycomimetic E-selectin ligand, in which the carboxylate group of the lead compound is substituted with a range of amide and isosteric analogs. Despite the expected loss of the salt-bridge interaction with Arg97, several amides retained or even improved the binding affinity. Co-crystal structures revealed conserved binding poses across the series, with consistent interactions involving the carbonyl oxygen of the amide and the key residues Tyr48 and Arg97. High-level quantum chemical calculations ruled out a direct correlation between carbonyl partial charges and affinity. Instead, a moderate correlation was observed between ligand binding and the out-of-plane pyramidality of the amide nitrogen, suggesting a favorable steric adaptation within the binding site. Molecular dynamics (MD) simulations revealed that high-affinity ligands exhibit enhanced solution-phase pre-organization toward the bioactive conformation, likely reducing the entropic penalty upon binding. Further analysis of protein–ligand complexes using Molecular mechanics/Generalized born surface area (MM-GB/SA) decomposition suggested minor lipophilic contributions from amide substituents. Taken together, this work underscores the importance of geometric and conformational descriptors, beyond classical electrostatics, in driving affinity in glycomimetic ligand design and provides new insights into the nuanced role of amides as carboxylate isosteres in protein–ligand recognition. Full article

Neutrophils, key effector cells of the innate immune system, combat pathogens through mechanisms including the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). While these responses are critical for host defense, prolonged elevation of ROS and dysregulated NETosis mediated by neutrophils have been implicated in autoimmune diseases, chronic inflammation, and cancer. In pancreatic ductal adenocarcinoma (PDAC), a highly aggressive and inflammatory malignancy, an increase in neutrophils infiltrating the tumor microenvironment promotes cancer progression and metastasis through increased ROS production and NET release. Using bioluminescence imaging with the reporter L-012 and NET assays, we assessed ROS and NET release, respectively, induced by phorbol myristate acetate and platelet-activating factor in bone-marrow-isolated neutrophils from wild-type and syngeneic myeloperoxidase (MPO)-deficient mice ex vivo. MPO deficiency impaired both ROS generation and NET release, establishing a positive correlation between these processes. In vivo analyses using subcutaneous and spontaneous murine PDAC models revealed elevated ROS in tumors, which were significantly reduced upon genetic deletion of host MPO or peptidyl arginine deiminase 4, an essential enzyme for NET formation, or after treatment with hydroxychloroquine, a NET inhibitor. Furthermore, luminol and 4-[¹⁸F]fluoro-1-naphthol ([¹⁸F]4FN), functional L-012 analogs, also enabled non-invasive detection of intratumoral ROS by bioluminescence and PET imaging in vivo, respectively; [¹⁸F]4FN PET showed a three-fold increased uptake in PDAC tumors versus muscle. PDAC tissues and blood-isolated neutrophils obtained from PDAC patients exhibited elevated ROS compared to controls ex vivo. Importantly, ROS levels correlated strongly with NET formation in patient samples. These findings reveal a bidirectional relationship between ROS and NETs and highlight the potential utility of L-012- and [¹⁸F]4FN-based PET imaging for monitoring NET-associated inflammation in PDAC in vivo. Full article

Resource-based regions play an indispensable role as strategic bases for national energy and raw material supply in the global industrialization and urbanization process. However, intensive and large-scale natural resource exploitation—particularly mineral extraction—often triggers dramatic land use/cover changes, leading to a series of problems including cultivated land degradation, ecological function deterioration, and human settlement environment degradation. However, a systematic understanding of the functional transitions within the land use system and their drivers in such regions remains limited. This study takes Shenmu City, a typical resource-based city in the ecologically vulnerable Loess Plateau, as a case study to systematically analyze the transition characteristics and driving mechanisms of land use functions from 2000 to 2020. By constructing an integrated “element–structure–function” analytical framework and employing a suite of methods, including land use transfer matrix, Spearman correlation analysis, and random forest with SHAP interpretation, we reveal the complex spatiotemporal evolution patterns of production–living–ecological functions and their interactions. The results demonstrate that Shenmu City has undergone rapid land use transformation, with the total transition area increasing from 27,394.11 ha during 2000–2010 to 43,890.21 ha during 2010–2020. Grassland served as the primary transition source, accounting for 66.5% of the total transition area, while artificial surfaces became the main transition destination, receiving 38.6% of the transferred area. The human footprint index (SHAP importance: 4.011) and precipitation (2.025) emerged as the dominant factors driving land use functional transitions. Functional interactions exhibited dynamic changes, with synergistic relationships predominating but showing signs of weakening in later periods. The findings provide scientific evidence and a transferable analytical framework for territorial space optimization and ecological restoration management not only in Shenmu but also in analogous resource-based regions facing similar development–environment conflicts. Full article

Kynurenic acid (KYNA) has recognized anti-inflammatory and immunosuppressive properties. Previous studies demonstrated that KYNA reduces TNF-α, S100A12, S100A8/9, and α-defensin production while increasing tumor necrosis factor-stimulated gene-6 protein (TSG-6) levels in rheumatoid arthritis. This study evaluated a synthetic KYNA analog’s effects on TNF-α, S100A8/9, S100A12, α-defensin, and interleukin-17 (IL-17) production and TSG-6 expression in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Peripheral blood mononuclear cells from 54 AS and 38 PsA patients and 11 healthy controls were stimulated with heat-inactivated Staphylococcus aureus (SA1). Parallel cultures were pretreated with the KYNA analog. Cytokine and alarmin concentrations were measured by ELISA. SA1 stimulation increased TNF-α, TSG-6, calprotectin, and α-defensin production, with minimal effects on S100A12 and none on IL-17. The KYNA analog significantly reduced SA1-induced TNF-α, calprotectin, and α-defensin levels and enhanced TSG-6 production, without affecting S100A12 or IL-17. Notably, the TNF-α inhibitory and TSG-6 stimulatory effects were inversely correlated. Conclusion: KYNA analogs may exert anti-inflammatory effects via TSG-6 upregulation, contributing to the suppression of key cytokines. These findings support further exploration of KYNA derivatives as therapeutic options in immune-mediated diseases including AS and PsA. Full article

Heterobimetallic iron–group 9 carbonyl cations, FeM(CO)_n⁺ (M = Rh, Ir; n = 9–11), were generated in the gas phase via pulsed laser vaporization within a supersonic expansion and characterized by infrared photodissociation spectroscopy in the carbonyl stretching region. By combining experimental spectra with density functional theory simulations, the geometric and electronic structures of these clusters were unambiguously assigned. Mass spectrometry and photodissociation results identified FeM(CO)₉⁺ as the saturated species for M = Rh and Ir, in contrast to the lighter cobalt analog FeCo(CO)₈⁺. The FeM(CO)₉⁺ cations adopt a C_4v-symmetric singlet ground-state structure with all carbonyl ligands terminally bound, corresponding to a (OC)₅Fe–M(CO)₄ configuration. These complexes can be formally described as combination products of the stable neutral Fe(CO)₅ and cationic M(CO)₄⁺ fragments. Analyses based on canonical molecular orbitals, Mayer bond orders, and fragment-based correlation diagrams reveal the presence of a dative Fe→M interaction in FeM(CO)₉⁺, which formally enables the heavier Rh/Ir metal center to attain an 18-electron configuration. However, this bond is weaker than a typical covalent single bond, as the key molecular orbitals involved possess antibonding character. This study provides important insights into the structure and bonding of heteronuclear transition metal carbonyl clusters, highlighting distinctive coordination behavior between late 3d and heavier 4d/5d congeners. Full article