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21 pages, 3956 KB  
Article
Pharmacokinetics of Ceftriaxone Encapsulated in Carrier Erythrocytes in Experimental Study
by Kulzhan Berikkhanova, Alexandr Gulyayev, Yernur Zakirov, Askhat Zhilkaidarov, Azhar Zhaisanova, Nurgul Daniyeva, Ardak Omarbekov, Gulsara Berikkhanova, Yessenkhan Sultan, Zhannat Zhakiyanova and Gulyash Tanysheva
Pharmaceutics 2026, 18(9), 1052; https://doi.org/10.3390/pharmaceutics18091052 - 25 Aug 2026
Abstract
Background/Objectives: Ceftriaxone (Ctx) is a third-generation cephalosporin widely used to treat infections caused by Gram-positive and Gram-negative bacteria. However, its clinical efficacy may be limited by rapid systemic elimination and suboptimal tissue distribution. Erythrocyte-based targeted drug delivery systems (TDDSs) have emerged as [...] Read more.
Background/Objectives: Ceftriaxone (Ctx) is a third-generation cephalosporin widely used to treat infections caused by Gram-positive and Gram-negative bacteria. However, its clinical efficacy may be limited by rapid systemic elimination and suboptimal tissue distribution. Erythrocyte-based targeted drug delivery systems (TDDSs) have emerged as a promising approach to prolong drug circulation and enhance site-specific accumulation. This study investigated the pharmacokinetic profile and tissue distribution of ceftriaxone encapsulated in autologous erythrocytes (RBC-Ctx) compared with free ceftriaxone (Free-Ctx) following intravenous administration in rats. Methods: Ceftriaxone was encapsulated into autologous rat erythrocytes using a hypoosmotic hemolysis loading technique. Drug-loaded erythrocytes are called pharmacocytes. Adult male Wistar rats received a single intravenous injection of Free-Ctx or RBC-Ctx at an equivalent ceftriaxone dose of 340 mg/kg. Plasma samples were collected over 24 h for pharmacokinetic analysis, while the liver, spleen, lungs, kidneys, heart, pancreas, and skeletal muscle were harvested at 1 and 12 h for tissue distribution studies. Ceftriaxone concentrations were quantified by high-performance liquid chromatography with UV detection. Results: Erythrocyte encapsulation significantly modified the pharmacokinetic behavior of ceftriaxone. Compared with Free-Ctx, RBC-Ctx prolonged the elimination half-life (4.4 ± 0.6 vs. 1.8 ± 0.1 h), increased systemic exposure (AUC0–last, 1.6 ± 0.1 vs. 1.2 ± 0.2 mg·h/mL), reduced total body clearance (218.2 ± 11.0 vs. 294.0 ± 48.8 mL/h/kg), and increased the apparent volume of distribution at steady state (688.3 ± 61.0 vs. 435.0 ± 23.1 mL/kg). In addition, RBC-Ctx was associated with a distinct relative tissue-distribution pattern of ceftriaxone, particularly in reticuloendothelial system-rich organs such as the liver and spleen, while ceftriaxone remained detectable in several tissues at 12 h after administration. In contrast, ceftriaxone concentrations following Free-Ctx declined markedly or became undetectable over the same period. Conclusions: Encapsulation of ceftriaxone into autologous erythrocytes substantially prolonged systemic circulation, enhanced drug exposure, reduced clearance, and altered the relative tissue distribution of ceftriaxone. These findings demonstrate that erythrocyte-based carriers effectively modulate ceftriaxone pharmacokinetics and tissue distribution, supporting their potential as a targeted antibiotic delivery platform for improving antimicrobial therapy, particularly for infections involving reticuloendothelial system-associated tissues. Further studies in experimental models of infection and inflammation are warranted to evaluate therapeutic efficacy under pathological conditions and to optimize this delivery strategy. Full article
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20 pages, 451 KB  
Review
Safety and Efficacy of Mesenchymal Stem Cell Therapy in Aging Frailty: A Systematic Review
by Eleni Poutouri, Maria Sotiropoulou, Michael Potoupnis, Georgios Koliakos, Evanthia Kassi, Symeon Tournis and Panagiotis Anagnostis
Int. J. Mol. Sci. 2026, 27(17), 7596; https://doi.org/10.3390/ijms27177596 - 25 Aug 2026
Abstract
Aging frailty is a multifactorial geriatric syndrome characterized by reduced physiological reserve across multiple interrelated systems, leading to increased vulnerability to adverse health outcomes. Mesenchymal stem cells (MSCs) have emerged as a potential therapeutic intervention due to their immunomodulatory and regenerative properties. This [...] Read more.
Aging frailty is a multifactorial geriatric syndrome characterized by reduced physiological reserve across multiple interrelated systems, leading to increased vulnerability to adverse health outcomes. Mesenchymal stem cells (MSCs) have emerged as a potential therapeutic intervention due to their immunomodulatory and regenerative properties. This systematic review aimed to evaluate the available clinical evidence regarding the safety and efficacy of MSC administration in individuals with aging frailty. A systematic literature search was conducted in PubMed, Scopus, and the Cochrane Library from database inception to 15 April 2026. Only randomized controlled trials (RCTs) were eligible. Data were extracted according to study design, participants’ characteristics, MSC source and dosing, safety outcomes, functional performance measures, quality of life (QoL) indices, and inflammatory, immune, and vascular biomarkers. Three RCTs met the inclusion criteria, comprising a total of approximately 208 participants. MSC administration was well-tolerated, with no treatment-related serious adverse events reported. Signals of improvement were reported in mobility-related and physical performance outcomes, although the magnitude and consistency of the response varied across studies. A dose-dependent increase in 6 min walk distance was observed at nine months in one trial, while improvements in SPPB, TUG, and grip strength were reported in the other studies. Additionally, MSC therapy was associated with QoL improvement and reduction in circulating pro-inflammatory cytokine concentrations. MSC administration was also associated with changes in immune-cell activation and a dose-dependent reduction in circulating sTIE2. Because of substantial clinical and methodological heterogeneity among the included trials, a quantitative meta-analysis was not performed. Current randomized evidence remains limited but suggests that intravenous MSC therapy is generally well tolerated in older adults with aging frailty and may produce clinically relevant signals of improvement in mobility-related functional outcomes, quality of life, and selected inflammatory, immune, and vascular biomarkers. However, the small number of trials, heterogeneity in MSC source, dose, endpoints, and follow-up duration, and the exploratory nature of much of the evidence preclude definitive conclusions regarding efficacy. Larger, adequately powered trials with standardized frailty endpoints are required, while future trials specifically targeting sarcopenia should apply consensus diagnostic criteria and direct measures of muscle quantity, strength, and physical performance. Full article
(This article belongs to the Special Issue Skeletal Muscle Aging: Mechanisms, Biomarkers, and Interventions)
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20 pages, 1984 KB  
Article
Urinary Proteome Profiling by Several Methods Identifies Titin as the Most-Differentiating Noninvasive Urinary Biomarker of Disease Severity in Becker Muscular Dystrophy
by Kimchi K. Le, Emily H. Canessa, Corrine M. Stahura, Jenna Mayers, Katie A. Edwards, Marissa Barbieri, Eric P. Hoffman and Yetrib Hathout
Proteomes 2026, 14(3), 43; https://doi.org/10.3390/proteomes14030043 - 25 Aug 2026
Abstract
Background: Beckers muscular dystrophy (BMD) is a clinically heterogeneous dystrophinopathy caused by in-frame mutations in the dystrophin gene, resulting in variable disease severity. This variability limits the effectiveness of standardized functional measures for tracking progression. Circulating biomarkers, including urinary titin fragments generated during [...] Read more.
Background: Beckers muscular dystrophy (BMD) is a clinically heterogeneous dystrophinopathy caused by in-frame mutations in the dystrophin gene, resulting in variable disease severity. This variability limits the effectiveness of standardized functional measures for tracking progression. Circulating biomarkers, including urinary titin fragments generated during muscle injury, offer a promising non-invasive approach for assessing disease status. Methods: Mass spectrometry-based urinary proteomic profiling identified titin fragments as candidate biomarkers of muscle injury in BMD. These titin fragments were validated by two independent methods, targeted mass spectrometry and ELISA, using subsets of ambulatory BMD, non-ambulatory BMD and age matched healthy volunteers. Results: Urinary titin levels were significantly elevated by 4.56-fold and 2.32-fold in ambulatory and non-ambulatory BMD patients, respectively, compared with healthy controls. Titin levels also distinguished ambulatory from non-ambulatory BMD patients, demonstrating potential utility for monitoring disease progression and therapeutic response. Conclusions: Urinary titin fragments represent a promising non-invasive biomarker for BMD, with potential applicability to related neuromuscular disorders and clinical trials evaluating disease progression and treatment efficacy. Full article
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23 pages, 44020 KB  
Article
Impacts of Solar Radiation Modification on Extreme Climate Indices in the Philippines
by Patricia Ann A. Jaranilla-Sanchez, Hanz Lester C. Lunas, Catherine B. Gigantone, Michael Jason L. Mozo, Emmanuel Zeus S. Gapan, Keane Carlo G. Lomibao, Allan T. Tejada and Rodel D. Lasco
Climate 2026, 14(9), 173; https://doi.org/10.3390/cli14090173 - 24 Aug 2026
Abstract
The rising global temperature and changing climate patterns have increased the frequency and intensity of extreme heat events, droughts, and heavy precipitation, significantly affecting agriculture, water resources, and ecosystems. Solar radiation management (SRM) has been proposed as a geoengineering strategy to mitigate these [...] Read more.
The rising global temperature and changing climate patterns have increased the frequency and intensity of extreme heat events, droughts, and heavy precipitation, significantly affecting agriculture, water resources, and ecosystems. Solar radiation management (SRM) has been proposed as a geoengineering strategy to mitigate these effects by reducing incoming solar radiation. This study evaluated future trends and variability in rainfall and temperature extremes in the Philippines under GeoMIP (G6Solar and G6Sulfur) and ScenarioMIP (SSP2-4.5 and SSP5-8.5) projections. Using five General Circulation Models (GCMs) and a suite of 10 climate indices recommended by the Expert Team on Climate Change Detection and Indices (ETCCDI), changes in extreme precipitation and temperature across different climate zones in the Philippines were assessed. Climate projections for the future (2041–2070) scenario were analyzed using bias correction, downscaling, and spatial interpolation techniques. Trend analysis was evaluated using the Mann–Kendall test and Sen’s slope estimator, while variability was assessed through statistical methods. The results show widespread warming and increased extreme precipitation, but these trends vary significantly across regions. Non-uniform responses emerge across scenarios, with some northern regions experiencing decreases in specific precipitation indices despite the broader warming trend under SRM and non-SRM conditions. These findings provide critical insights into the potential impacts of SRM on future climate extremes in the Philippines and guidance on climate policy recommendations for decision-makers and stakeholders. Full article
(This article belongs to the Section Climate Adaptation and Mitigation)
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17 pages, 25133 KB  
Article
Observed and Simulated Decadal Variability of Precipitation in North Africa and the Mediterranean: Insights from ERA5 Reanalysis and CORDEX-CORE Simulations
by Faustin Katchele Ogou, Khadija Arjdal and Fatima Driouech
Climate 2026, 14(9), 172; https://doi.org/10.3390/cli14090172 - 24 Aug 2026
Abstract
Climate change and variability pose serious threats to natural and human systems. The Mediterranean and North Africa (MNA) are among the world’s climate change hotspots. An in-depth understanding of the decadal climate variability in this region is critical to support planning and management, [...] Read more.
Climate change and variability pose serious threats to natural and human systems. The Mediterranean and North Africa (MNA) are among the world’s climate change hotspots. An in-depth understanding of the decadal climate variability in this region is critical to support planning and management, as well as adaptation in important sectors such as water resources. Therefore, in this study, fifth-generation ECMWF atmospheric reanalysis (ERA5) precipitation data and the outputs of the Coordinated Regional Downscaling Experiment-COmmon Regional Experiment (CORDEX-CORE) regional models were used to characterize the decadal precipitation variability in MNA and its sub-regions (Western North Africa: WNA, Sahara: SAH, southern Mediterranean: SMED, and northern Mediterranean: NMED). The models showed overestimation in most areas and underestimation in a few areas relative to the ERA5 data, with the magnitude varying by region and season. The positive biases obtained from the regional climate models (RCMs) were higher than the positive biases obtained from the general circulation models (GCMs). The wet biases were dominant during the annual, summer, and autumn seasons over MNA and its sub-regions. Negative biases were mostly associated with GCMs, mainly HadGEM2-ES and/or NorESM1-M; meanwhile, they were linked with RCMs such as CCLM5-0-15 and/or RegCM4_v7 and were mostly obtained in winter and spring. The multi-model mean (MME) was better at reproducing the decadal precipitation patterns over MNA, SMED, and NMED at all time scales, while REMO2015-NorESM1-M and the MME performed better than the remaining models at the annual time scale over WNA and SAH. These findings are useful for improving climate modeling, the water resources management and related sectors, and climate adaptation strategies in the region, especially in North Africa. The short-period coverage of the simulated data available for this study constitutes a limitation to the findings. Full article
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19 pages, 3556 KB  
Article
Nonlinear Dynamics of Social Exclusion via a Dynamic Extension of the Classical “Market for Lemons” Theory: Scapegoating as a Critical Phenomenon and Optimal Intervention Strategies
by Yasuko Kawahata
Games 2026, 17(5), 44; https://doi.org/10.3390/g17050044 - 24 Aug 2026
Abstract
Akerlof’s classical theory of the “Market for Lemons,” which conceptualizes adverse selection driven by information asymmetry, established the foundation of information economics. While the traditional model assumes static equilibria among a limited number of agents, analyzing its behavioral dynamics within large-scale, complex network [...] Read more.
Akerlof’s classical theory of the “Market for Lemons,” which conceptualizes adverse selection driven by information asymmetry, established the foundation of information economics. While the traditional model assumes static equilibria among a limited number of agents, analyzing its behavioral dynamics within large-scale, complex network environments remains a highly relevant task in computational social science. This study extends the classical lemon market model into a nonlinear dynamical system on adaptive networks. We mathematically elucidate macro-level social phase transitions—specifically structural exclusion such as scapegoating and collective ostracism—induced by computational cognitive limits, and evaluate optimal intervention strategies to mitigate these systemic failures. Multi-agent simulations utilizing large-scale tensor operations demonstrate that autonomous edge rewiring under incomplete information does not merely result in the uniform displacement of high-quality goods as predicted by static theory. Instead, the network self-organizes into an irreversible structural division: a core group of influential agents monopolizes high-quality information, while marginalized agents are isolated into a peripheral “lemon echo chamber” where only low-quality information circulates. To address this structural pathology under a resource constraint limiting intervention to 10% of the total agents, we evaluated two distinct approaches. The results indicate that providing informational support to influential hubs functions as a trap that exacerbates systemic inequality, superficially elevating the overall market evaluation but permanently fixing the exclusion gap. Conversely, the forced maintenance and protection of “weak ties” bridging disconnected clusters constitutes the mathematically optimal solution to dissolve fragmentation, effectively eliminating the price gap and facilitating social inclusion. Furthermore, this study demonstrates that the mechanism of social exclusion exhibits strong hysteresis effects. A distinct tipping point governs the progression toward a fragmented lemon echo chamber. Interventions implemented after crossing this critical threshold fail to restore the system to its baseline state despite identical resource expenditure, confirming the presence of an irreversible phase transition. These findings establish that the collapse dynamics outlined in the classical lemon market serve as a generalized model for explaining contemporary collective ostracism driven by information cascades. Consequently, the analysis highlights the necessity of early intervention prior to critical thresholds and the systemic preservation of structural bypasses rather than post-hoc remediation. Full article
(This article belongs to the Section Algorithmic and Computational Game Theory)
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25 pages, 51902 KB  
Article
Serum Escape Landscape of SARS-CoV-2 Omicron JN.1 and XEC RBD Under COVID-19 Vaccine Breakthrough Immunity in China
by Chengwei Shao, Jianguang Fu, Fei Deng, Huiyan Yu, Huan Fan, Yanjun Chen, Ke Xu, Mingwei Wei, Siyue Jia, Xiaoyan Jia, Liguo Zhu and Jingxin Li
Microorganisms 2026, 14(9), 1872; https://doi.org/10.3390/microorganisms14091872 - 23 Aug 2026
Viewed by 147
Abstract
Population immune pressure from vaccination and prior infection continues to drive the evolution of SARS-CoV-2. Systematic characterization of RBD mutations under complex immune backgrounds is essential for understanding viral adaptation and evolutionary trajectories. Here, we applied a deep mutational scanning (DMS) to comprehensively [...] Read more.
Population immune pressure from vaccination and prior infection continues to drive the evolution of SARS-CoV-2. Systematic characterization of RBD mutations under complex immune backgrounds is essential for understanding viral adaptation and evolutionary trajectories. Here, we applied a deep mutational scanning (DMS) to comprehensively map the neutralization escape landscape of the Omicron variant JN.1 and its descendant lineage XEC, under immune pressure from individuals who experienced Omicron breakthrough infections following three doses of inactivated vaccines. A neutralization escape map for the single amino acid substitutions in the RBD of JN.1 or XEC was generated, and the escape efficiency of each mutation was determined. The results show that RBD escape mutations are hierarchically organized: low-intensity signals are widespread, whereas high-intensity escape is confined to a few key sites. These escape mutations are not confined solely to the receptor-binding motif (RBM) but are broadly distributed across the entire RBD. Many escape sites could accommodate multiple amino acid substitutions. Integration of DMS data with genomic surveillance of circulating variants from 2024 to 2025 revealed significant overlap between experimentally identified escape sites and mutations observed in natural isolates. This overlap increased substantially in 2025, with site concordance rising from 27.17% and 26.81% to 45.09% and 47.10% for JN.1 and XEC, respectively. The natural prevalence of these escape mutations is further shaped by factors such as receptor-binding affinity, protein stability, and epistatic interactions. Overall, our findings suggest that SARS-CoV-2 antigenic evolution follows the pattern of multiple pathways within a constrained space, providing new insights into the adaptive mechanisms of Omicron-derived variants under hybrid immune pressure. Full article
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20 pages, 2695 KB  
Article
Hypotension Requiring Vasopressor Support After Endovascular Thrombectomy: Predictors and Neurological Consequences
by Justyna Zielińska-Turek, Dariusz Kosior, Jolanta Kołakowska and Małgorzata Dorobek
J. Clin. Med. 2026, 15(17), 6521; https://doi.org/10.3390/jcm15176521 - 23 Aug 2026
Viewed by 83
Abstract
Background/Objectives: Endovascular thrombectomy (EVT) has transformed the treatment of acute ischaemic stroke due to large-vessel occlusion, yet peri-procedural haemodynamic instability may compromise penumbral perfusion and neurological recovery. We assessed the frequency, determinants and clinical consequences of post-procedural hypotension after EVT. Methods: [...] Read more.
Background/Objectives: Endovascular thrombectomy (EVT) has transformed the treatment of acute ischaemic stroke due to large-vessel occlusion, yet peri-procedural haemodynamic instability may compromise penumbral perfusion and neurological recovery. We assessed the frequency, determinants and clinical consequences of post-procedural hypotension after EVT. Methods: We retrospectively reviewed 201 consecutive adults who underwent endovascular thrombectomy for anterior-circulation large-vessel occlusion at a single tertiary centre over a period of eight years, from 1 January 2017 to 31 January 2025. Post-procedural hypotension was defined as hypotension requiring initiation of a continuous noradrenaline infusion within 24 h of the procedure. Comorbidities, anaesthetic modality (general anaesthesia [GA] or conscious sedation [CS]), National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores, and in-hospital mortality were recorded. Logistic regression identified independent predictors of hypotension. Results: Fifty-five patients (27.4%) developed post-procedural hypotension. They presented with more severe strokes (NIHSS 16.0 ± 5.0 vs. 13.7 ± 5.0; p = 0.002), had higher NIHSS scores at day 2 (14.0 ± 6.9 vs. 9.4 ± 6.7; p < 0.001) and day 7 (p = 0.003), and displayed markedly higher in-hospital mortality (50.9% vs. 20.5%; p < 0.001). In an ordinal analysis of the day 7 modified Rankin Scale with death coded as 6, hypotension was associated with a shift towards greater disability (common OR 2.57, 95% CI 1.40–4.72; p = 0.002). In an exploratory model, each additional 10 min of door-to-groin time was independently associated with hypotension (adjusted OR 1.10, 95% CI 1.03–1.18; p = 0.003). Independent predictors of hypotension were baseline NIHSS (adjusted OR 1.11 per point, 95% CI 1.04–1.19; p = 0.003) and active malignancy (adjusted OR 2.90, 95% CI 1.04–8.09; p = 0.042). Hypotension occurred with similar frequency under GA and CS (28.6% vs. 24.6%; adjusted OR 1.12, 95% CI 0.54–2.34; p = 0.766). Conclusions: Post-EVT hypotension is common and associated with poorer early neurological recovery and a more than two-fold higher in-hospital mortality rate. Its independent predictors were baseline stroke severity and active malignancy. Patients with severe stroke or active cancer may warrant intensified haemodynamic surveillance after thrombectomy. Procedural delay emerged as the only modifiable predictor identified and warrants prospective evaluation. Full article
(This article belongs to the Section Clinical Neurology)
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29 pages, 1243 KB  
Review
The Plume Model of the Mass–Flux Convective Parameterization Schemes
by Cristian V. Vraciu
Atmosphere 2026, 17(9), 815; https://doi.org/10.3390/atmos17090815 - 23 Aug 2026
Viewed by 194
Abstract
The general circulation models are used for climate predictions and weather forecasting, resolving governing prognostic equations at resolutions at which the convection is typically unresolved. As convection is responsible for important feedback in the climate system and is associated with severe weather events, [...] Read more.
The general circulation models are used for climate predictions and weather forecasting, resolving governing prognostic equations at resolutions at which the convection is typically unresolved. As convection is responsible for important feedback in the climate system and is associated with severe weather events, the climate and weather models must estimate the convection as a function of the resolved mean state of the atmosphere. This procedure is called convective parameterization, and the specific approach in which this task is achieved depends on the specific parameterization scheme employed by the general circulation model. However, almost all of the modern parameterization schemes are based on the same theoretical framework. Although state-of-the-art parameterization schemes still struggle to model convective transport and fractions of convective clouds accurately, limited attempts to change the fundamental theoretical bases have been made in recent years. The aim of this article is to discuss the theoretical bases under which the plume model is introduced in the mass-flux convective parameterization schemes and how these bases have changed in recent years as an attempt to change some of the current problems of the mass-flux parameterizations. This review examines the evolution of the plume model underlying mass–flux convection parameterizations. The discussion focuses on five key topics: (i) the interpretation of convective plumes as representations of cloud ensembles, (ii) entrainment and detrainment assumptions, (iii) prognostic formulations and convective memory, (iv) unified formulations for shallow and deep convection, and (v) challenges associated with convection in the gray zone. The review argues that many recent developments can be interpreted as relaxations of assumptions originally associated with the steady-state plume framework, and discusses the implications of these relaxations for the physical interpretation of mass–flux parameterizations. Full article
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18 pages, 11554 KB  
Article
Plasma-Derived Extracellular Vesicle microRNAs in Multiple Sclerosis: An Exploratory Case-Control Study on Phenotypic Discrimination
by Oana Vrînceanu, Doina Manu, Smaranda Maier, Claudia Bănescu, Ana-Claudia Carstea and Rodica Bălașa
Int. J. Mol. Sci. 2026, 27(17), 7530; https://doi.org/10.3390/ijms27177530 - 22 Aug 2026
Viewed by 183
Abstract
Distinguishing relapsing–remitting multiple sclerosis (RRMS) from secondary-progressive disease (SPMS) remains a clinical challenge, as no single laboratory test reliably identifies the transition. We explored whether plasma extracellular-vesicle (EV) microRNAs could separate the two phenotypes. Four candidate EV-miRNAs: miR-30a-5p, miR-223-5p, miR-155-5p, and miR-146a-5p, were [...] Read more.
Distinguishing relapsing–remitting multiple sclerosis (RRMS) from secondary-progressive disease (SPMS) remains a clinical challenge, as no single laboratory test reliably identifies the transition. We explored whether plasma extracellular-vesicle (EV) microRNAs could separate the two phenotypes. Four candidate EV-miRNAs: miR-30a-5p, miR-223-5p, miR-155-5p, and miR-146a-5p, were quantified by qRT-PCR in plasma-derived EVs from 13 healthy controls (HC), 7 RRMS, and 16 SPMS patients, normalized to miR-16-5p. EVs were characterized by electron microscopy, dynamic light scattering, and zeta potential, confirming vesicles of expected morphology, size, and negative surface charge. Two miRNAs were informative. miR-155-5p was significantly downregulated in both RRMS and SPMS versus controls but did not differentiate the phenotypes (AUC 0.52), behaving as a disease-general marker. In contrast, miR-223-5p was selectively reduced in SPMS, to approximately one-quarter of control abundance, and provided the only signal distinguishing progressive from relapsing disease (AUC 0.73; rank-biserial −0.46). miR-30a-5p and miR-146a-5p were uninformative. These findings, consistent with the circulating/EV literature, suggest EV-miR-223-5p as a candidate marker of the progressive phenotype and EV-miR-155-5p as a disease indicator. Given the small cohort and near-detection-limit measurements, the study is hypothesis-generating and requires validation in larger, longitudinal cohorts. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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25 pages, 6540 KB  
Article
Association of the Pan-Immune-Inflammation Value-to-Albumin Ratio as a Novel Cardiovascular Disease Predictor in Type 2 Diabetes: A Prospective Cohort Study
by Fangyuan Liu, Xinghua Yang, Bo Gao, Yanxia Luo, Lixin Tao and Xiuhua Guo
Biomedicines 2026, 14(9), 1878; https://doi.org/10.3390/biomedicines14091878 - 22 Aug 2026
Viewed by 141
Abstract
Objectives: Individuals with type 2 diabetes (T2D) remain at high cardiovascular disease (CVD) risk. The pan-immune-inflammation value (PIV) integrates circulating neutrophils, monocytes, platelets, and lymphocytes but does not capture albumin-related nutritional and inflammatory reserve. We investigated associations between the PIV-to-albumin ratio (PIVA) [...] Read more.
Objectives: Individuals with type 2 diabetes (T2D) remain at high cardiovascular disease (CVD) risk. The pan-immune-inflammation value (PIV) integrates circulating neutrophils, monocytes, platelets, and lymphocytes but does not capture albumin-related nutritional and inflammatory reserve. We investigated associations between the PIV-to-albumin ratio (PIVA) and incident CVD, cardiovascular mortality, and disease progression in individuals with T2D. Methods: This prospective study included 15,355 UK Biobank participants with T2D and no baseline CVD. PIVA was calculated from peripheral blood cell counts and serum albumin and was natural log-transformed. Fine–Gray competing-risk and cause-specific Cox models were used to evaluate incident CVD and cardiovascular mortality. Multi-state models characterized transitions from T2D to CVD and death. We also examined nonlinear associations, renal biomarker mediation, joint associations with the CVD polygenic risk score and triglyceride–glucose index, sensitivity analyses, and external validation of cardiovascular mortality in the National Health and Nutrition Examination Survey. Results: During median follow-ups of 12.94 years for incident CVD and 14.49 years for cardiovascular mortality, 4829 incident CVD events and 514 cardiovascular deaths occurred. Each 1-unit increase in lnPIVA was associated with higher risks of incident CVD (subdistribution hazard ratio [sHR], 1.140; 95% confidence interval [CI], 1.088–1.194) and cardiovascular mortality (sHR, 1.449; 95% CI, 1.247–1.684). Associations were nonlinear. Higher lnPIVA was also associated with transitions from T2D to CVD, from T2D directly to cardiovascular death, and from incident CVD to cardiovascular death. Cystatin C explained a larger proportion of these associations than creatinine. Elevated lnPIVA identified excess cardiovascular risk across strata of genetic susceptibility and insulin resistance, and the findings were generally supported by sensitivity and external validation analyses. Conclusions: lnPIVA was associated with incident CVD, cardiovascular mortality, and adverse cardiovascular transitions in individuals with T2D. As an immune-inflammatory and albumin-based index, PIVA may help identify high-risk individuals beyond conventional cardiometabolic and genetic risk profiles. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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19 pages, 1188 KB  
Review
Dynamic Modeling of Circulating Fluidized Bed Power Plants for Flexible Operation: Progress, Challenges and Future
by Xiannan Hu, Haowen Wu, Ruiqi Bai, Tong Wang, Tuo Zhou, Man Zhang and Hairui Yang
Energies 2026, 19(17), 3953; https://doi.org/10.3390/en19173953 - 22 Aug 2026
Viewed by 88
Abstract
The increasing penetration of renewable energy has significantly intensified the demand for flexible operation of thermal power plants, making dynamic simulation an essential tool for understanding transient behaviors and developing advanced operational strategies for circulating fluidized bed (CFB) power plants. This review critically [...] Read more.
The increasing penetration of renewable energy has significantly intensified the demand for flexible operation of thermal power plants, making dynamic simulation an essential tool for understanding transient behaviors and developing advanced operational strategies for circulating fluidized bed (CFB) power plants. This review critically examines the existing dynamic modeling approaches for industrial-scale CFB power plants, with particular emphasis on their applicability to flexibility studies. Existing CFB flue-gas side models are systematically classified into three categories: 3D physics-based CFD models, behavioral/data-driven models, and semi-empirical mechanistic models. Their characteristics are critically compared in terms of spatial and temporal scales, empirical dependence, model generality, computational and implementation burden, and applicability to CFB flexibility studies. Dynamic modeling of the steam–water cycle is also reviewed, showing that it has reached a relatively mature stage owing to well-established thermo-hydraulic theories and standardized modeling platforms. The current research bottleneck is therefore identified as the dynamic coupling between the flue-gas side and the steam–water cycle for integrated CFB whole-plant simulation. Based on the comparative analysis, semi-empirical mechanistic models are identified as a particularly suitable framework for industrial-scale CFB flexibility studies requiring minute-to-hour transient simulation, physical interpretability, and whole-plant coupling. Finally, future research directions are discussed, highlighting how integrated dynamic models can support CFB flexibility-enhancement technologies and the development of new-generation coal-fired power plants. Full article
(This article belongs to the Section B2: Clean Energy)
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14 pages, 252 KB  
Review
Liquid Biopsy in Head and Neck Squamous Cell Carcinoma: A Molecular Perspective on Circulating Biomarkers and Their Clinical Translation
by Francesca Cascone, Gabriele Riccardi, Dario Benelli, Riccardo Maurizi, Camilla Laureti, Carla Petrella, Carlo Cogoni, Antonio Minni and Christian Barbato
Curr. Issues Mol. Biol. 2026, 48(9), 853; https://doi.org/10.3390/cimb48090853 - 22 Aug 2026
Viewed by 77
Abstract
Liquid biopsy, the analysis of tumor-derived material in blood, saliva, and other body fluids, is increasingly explored for the diagnosis, surveillance, and molecular characterization of head and neck squamous cell carcinoma (HNSCC). Its performance, however, is not uniform across the disease, and the [...] Read more.
Liquid biopsy, the analysis of tumor-derived material in blood, saliva, and other body fluids, is increasingly explored for the diagnosis, surveillance, and molecular characterization of head and neck squamous cell carcinoma (HNSCC). Its performance, however, is not uniform across the disease, and the reason is fundamentally molecular. human papillomavirus (HPV)-positive oropharyngeal cancers carry viral oncogenes that are absent from the host genome and therefore provide a near ideal, tumor specific circulating marker, whereas HPV-negative tumors are driven by a heterogeneous somatic landscape that offers no single universal target. In this narrative review, we adopt a molecular perspective. We first examine the biological origin of circulating tumor DNA and of the other analytes that liquid biopsy can interrogate including circulating tumor HPV DNA, viral transcripts, microRNAs, extracellular vesicles, and methylation signatures. We then consider how analytical platforms, from droplet digital PCR to next generation and ultrasensitive whole-genome sequencing, translate these molecules into measurements. Only afterward do we discuss the clinical questions, organized by clinical objective rather than by individual study: diagnosis and early detection, prognosis and risk stratification, treatment response monitoring, minimal residual disease and surveillance, and biomarker guided de-escalation in HPV-positive disease. Twelve registered clinical trials, involving approximately 1183 patients, are presented as illustrations of these questions. We close on the biological and technical gaps that still separate promising signals from clinical practice, and on the multi analyte and dynamic strategies most likely to bridge them. At present, liquid biopsy should be regarded as a complementary tool rather than as a replacement for established clinicopathological assessment. Full article
(This article belongs to the Special Issue Molecular Mechanism of HPV’s Involvement in Cancers, 2nd Edition)
22 pages, 289 KB  
Article
Teachers’ Uses and Perceptions of Generative AI in North Rhine-Westphalia, Germany: A DigCompEdu-Informed Analysis
by Eucidio Pimenta Arruda and Tobias Hölterhof
Educ. Sci. 2026, 16(8), 1348; https://doi.org/10.3390/educsci16081348 - 21 Aug 2026
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Abstract
The diffusion of generative artificial intelligence has moved educational debate beyond access to new tools, placing teacher work, pedagogical mediation, assessment, and digital competence under renewed pressure. This article examines teachers’ perceptions, declared uses, and forms of engagement with generative AI in Gymnasien [...] Read more.
The diffusion of generative artificial intelligence has moved educational debate beyond access to new tools, placing teacher work, pedagogical mediation, assessment, and digital competence under renewed pressure. This article examines teachers’ perceptions, declared uses, and forms of engagement with generative AI in Gymnasien (academic-track secondary schools) and Gesamtschulen (comprehensive secondary schools) in North Rhine-Westphalia, Germany. The study is based on an anonymous and voluntary online questionnaire circulated through school leaderships. The operational database comprised 204 records, while the main analysis was based on 156 completed questionnaires. Closed-item responses were examined through descriptive statistics and interpreted through DigCompEdu and its AI-related supplement. The findings indicate an asymmetrical incorporation of generative AI across teachers’ work. Its presence is stronger in preparation, organisation, professional reflection, and risk awareness than in direct classroom mediation, process-oriented assessment, and institutionally supported student use. The strongest contrasts concern perceived student overreliance on AI-generated answers, the need to adapt assessment practices, limited school-level guidance, and weak use of AI-supported process monitoring. Rather than interpreting this imbalance as a simple delay in adoption, the article argues that teacher competence in relation to generative AI is produced through the interaction between professional judgement, pedagogical purposes, and institutional conditions. It therefore cannot be reduced to an individual technical attribute. Full article
46 pages, 39569 KB  
Article
Dyed Not Dead: A Pilot Study of Dye Analysis in Preindustrial Textile Case Studies from Icelandic Collections Using FORS and Spectragryph
by Noemí Cubas Martín and Ian M. King
Heritage 2026, 9(8), 332; https://doi.org/10.3390/heritage9080332 - 21 Aug 2026
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Abstract
In Iceland, dyed textiles carried meanings beyond aesthetics and function. Through textile production and circulation, woollen cloth, including vaðmál as one historically important example, became central to the Icelandic economy and offers a material perspective on technological practice, exchange systems, and regional connections. [...] Read more.
In Iceland, dyed textiles carried meanings beyond aesthetics and function. Through textile production and circulation, woollen cloth, including vaðmál as one historically important example, became central to the Icelandic economy and offers a material perspective on technological practice, exchange systems, and regional connections. This paper presents a pilot methodological study exploring the combined use of fibre optic reflectance spectroscopy (FORS) and a reference corpus developed in Spectragryph for the preliminary assessment of possible dye classes in preindustrial textile case studies from Icelandic collections. The approach provides a rapid, portable, and non-invasive framework for spectral comparison prior to complementary molecular analysis, with targeted LC–MS of selected archaeological textiles planned as the next phase of the research. Following botanical and ethnographic research, a reference corpus of 351 wool samples was assembled, including undyed fleece controls, experimentally dyed fibres, and ethnographic dyed yarns preserved in museum collections. Seven case studies are presented, comprising four archaeological textiles and three early modern ecclesiastical textiles preserved in the collections of the National Museum of Iceland. The spectra show reflectance features consistent with possible indigoid and anthraquinone-related dye classes in several of the analysed textiles, whereas possible flavonoid- and tannin-related patterns generally remain non-diagnostic. At the same time, degradation, contamination, natural fleece pigmentation, and overlapping chromophoric signals frequently complicate interpretation, particularly in archaeological materials and darker tonal ranges. The study illustrates the potential of FORS combined with structured spectral comparison as a non-invasive first-stage methodology for dye analysis in Icelandic textile case studies, while highlighting the limitations of reflectance-based interpretation and the need for complementary molecular analysis for definitive compound-level identification. Full article
(This article belongs to the Special Issue Dyes in History and Archaeology 44)
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