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22 pages, 4637 KB

Open AccessArticle

The Reconstitution of the Macrophage Niche Reveals Dynamic Transcriptional and Renal Macrophage–Epithelial Communication Networks

by Mohammad Islamuddin, Lixuan Ji, Yilin Chen, Kejing Song, Calder R. Ellsworth, Jack Rappaport, Chenxiao Wang, Shumei Liu, Jay Kolls, Xiaojiang Xu and Xuebin Qin

Cells 2026, 15(12), 1102; https://doi.org/10.3390/cells15121102 (registering DOI) - 18 Jun 2026

Abstract

Renal-resident macrophages (RMs) are essential regulators of kidney homeostasis and repair, yet the mechanisms governing RM niche regeneration after acute depletion remain poorly defined. To overcome these limitations, we have developed an inducible human CD59- intermedilysin (hCD59-ILY) ablation system, enabling rapid, specific, and [...] Read more.

Renal-resident macrophages (RMs) are essential regulators of kidney homeostasis and repair, yet the mechanisms governing RM niche regeneration after acute depletion remain poorly defined. To overcome these limitations, we have developed an inducible human CD59- intermedilysin (hCD59-ILY) ablation system, enabling rapid, specific, and reversible depletion of targeted macrophage populations, and subsequent replenishment of RMs, followed by longitudinal scRNA-seq analysis of kidneys at baseline and days 1, 3, and 7 post-ablation. RM ablation triggered a rapid and sustained upregulation of Cx3cl1, predominantly in proximal tubular epithelial cells (PTC1/PTC2), establishing a persistent chemotactic niche signal that coincided with macrophage repopulation. Regenerating RMs transitioned from inflammatory/stress-associated states toward metabolically active and proliferative phenotypes enriched in glycolysis, oxidative phosphorylation, MYC, and cell-cycle programs, with attenuation of canonical inflammatory pathways. Cell–cell communication analysis revealed an early burst of intercellular signaling at day 1, followed by progressive normalization, with fibronectin (Fn1), osteopontin (Spp1), chemokine (Ccl), and amyloid precursor protein (App) axes emerging as key mediators of niche restoration. Transcriptional network analysis identified a conserved regulatory module (Tfe3, Mitf, Hif1a, Myc, Gabpa, Rcor1) coordinating macrophage differentiation and regenerative programming, linking metabolic adaptation to lineage reconstitution. Sub-clustering revealed five dynamically shifting RM subsets with distinct inflammatory, remodeling, proliferative, and surveillance states, reflecting a hierarchical regeneration process. Functional validation using clodronate-mediated depletion in Secreted Phosphoprotein 1 (Spp1) (Opn)-deficient mice demonstrated impaired macrophage repopulation, establishing osteopontin as a critical regulator of RM regeneration. Together, these data define a coordinated epithelial–immune circuit in which Cx3cl1-driven chemotaxis, Spp1-dependent signaling, and a core transcriptional network orchestrate macrophage niche reconstitution and kidney repair following acute immune cell ablation. Full article

(This article belongs to the Topic Biofabrication Technologies for Tissue Repair and Regeneration)

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15 pages, 2081 KB

Open AccessArticle

Change in Swallowing Function and Substance P Levels Associated with Nicergoline in Neurological Disease: A Pilot Study

by Jutikan Imsub, Pasiri Sithinamsuwan, Chanasak Hathaiareerugand, Yarnisar Sakunchit and Juthathip Suphanklang

J. Clin. Med. 2026, 15(12), 4728; https://doi.org/10.3390/jcm15124728 (registering DOI) - 18 Jun 2026

Abstract

Background/Objectives: Dysphagia is a prevalent consequence of neurological conditions, particularly stroke and Parkinson’s disease, leading to aspiration pneumonia and reduced quality of life. Currently, there are no specific recommendations for pharmacological therapy, although studies indicate that elevated substance P levels may improve [...] Read more.

Background/Objectives: Dysphagia is a prevalent consequence of neurological conditions, particularly stroke and Parkinson’s disease, leading to aspiration pneumonia and reduced quality of life. Currently, there are no specific recommendations for pharmacological therapy, although studies indicate that elevated substance P levels may improve swallowing function. While nicergoline is known to increase substance P, the role of its major metabolite, 10-methoxy-dihydro-lysergol (MDL), in this therapeutic effect remains unclear. This study examined the therapeutic effects of nicergoline and its correlation with substance P and MDL levels. Methods: This study conducted an open-label pilot study with historical controls in neurogenic patients with dysphagia. The primary outcome was improvement in the Gugging Swallowing Screen (GUSS) scores at week 12. Secondary outcomes included choking frequency, serum substance P levels, and the correlation between serum MDL levels and dysphagia enhancement. Inverse Probability Weighting (IPW) was employed to adjust for baseline confounders. Results: A total of 92 patients were analyzed: 26 in the nicergoline group (20 or 60 mg/day) and 66 in the historical control group. Compared to controls, the nicergoline group exhibited significantly higher median of GUSS scores (20 (IQR: 19–20) vs. 15 (IQR: 9–19), p < 0.001) and significantly lower median of choking frequency (6.43 (IQR 0–17) vs. 108 (IQR 13–201) 105.22, p < 0.001). The median substance P concentration in the therapy group was 4089.15 (IQR: 3336.13–4468.26) pg/mL. Patients receiving nicergoline showed a statistically significant elevation in substance P from baseline (p < 0.001). Pearson analysis revealed a negligible correlation between serum MDL and substance P levels (R² = 0.0349). Conclusions: Preliminary findings suggest that nicergoline may be associated with improvements in swallowing function in neurogenic dysphagia and a potential increase in substance P levels. The lack of correlation with serum MDL suggests that efficacy may not linearly depend on circulating metabolite concentrations. Further large-scale randomized controlled trials are warranted. Full article

(This article belongs to the Special Issue Ischemic Stroke: Diagnosis and Treatment)

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16 pages, 4357 KB

Open AccessArticle

Borrelia miyamotoi in Saint Petersburg and Leningrad Oblast, Russia: A Multi-Level Assessment of Ticks, Rodents, and Human Exposure

by Ivan Lyzenko, Olga Stukolova, Nikolay Tokarevich, Marina Sokolova, Regina Baimova, Islam Karmokov, Ekaterina Riabiko, Daria Grechishkina, Gelena Lunina and Vladimir Dedkov

Trop. Med. Infect. Dis. 2026, 11(6), 166; https://doi.org/10.3390/tropicalmed11060166 (registering DOI) - 18 Jun 2026

Abstract

Background: Borrelia miyamotoi is an emerging tick-borne pathogen causing relapsing fever in humans. Although Saint Petersburg and the surrounding Leningrad Oblast harbor a high abundance of ixodid ticks (I. ricinus, I. persulcatus), no integrated assessment has yet simultaneously addressed [...] Read more.

Background: Borrelia miyamotoi is an emerging tick-borne pathogen causing relapsing fever in humans. Although Saint Petersburg and the surrounding Leningrad Oblast harbor a high abundance of ixodid ticks (I. ricinus, I. persulcatus), no integrated assessment has yet simultaneously addressed pathogen circulation in vectors, reservoir hosts, and human populations in this specific northwestern region of Russia. Methods: During 2022–2024, we collected 1518 questing adult ticks and trapped 516 small mammals in Saint Petersburg and Leningrad Oblast. B. miyamotoi DNA was detected by real-time PCR. Sera from 3743 randomly selected volunteers (1553 from Saint Petersburg, 2190 from Leningrad Oblast) were tested for anti-B. miyamotoi IgG/IgM using a protein microarray (antigens: GlpQ, Vmps, flagellin). Infection rates and seroprevalence with 95% Wilson confidence intervals were compared using chi-square tests. Results: The overall tick infection rate was 3.78% (57/1506). I. ricinus had a significantly higher prevalence (4.94%; 95% CI: 3.67–6.60%) than I. persulcatus (2.29%; 95% CI: 1.39–3.74%; p = 0.011). Ticks from Leningrad Oblast also showed markedly elevated infection rates (4.98%; 95% CI: 3.75–6.58%) compared to those from Saint Petersburg (1.89%; 95% CI: 1.06–3.35%; p = 0.004). Small mammals exhibited substantially higher infection rates in Leningrad Oblast (39.44%; 95% CI: 31.78–47.65%) than in Saint Petersburg (13.90%; 95% CI: 10.76–17.78%; p < 0.001). Bank voles (Myodes glareolus) and yellow-necked mice (Apodemus flavicollis) were the main reservoirs; synanthropic rodents trapped within the city were found to be infected for the first time. No significant organotropism was detected, but positive correlations between infection in the heart, liver, and kidney suggested hematogenous dissemination. The overall human seroprevalence of B. miyamotoi was 1.71% (95% CI: 1.34–2.18%) and was significantly higher in Leningrad Oblast (2.19%; 95% CI: 1.66–2.89%) than in Saint Petersburg (1.03%; 95% CI: 0.64–1.67%; p = 0.010). In contrast, the seroprevalence of B. burgdorferi s. l. did not differ between the two regions (approximately 5.1%). Conclusions: This first comprehensive, multi-level investigation in Saint Petersburg and Leningrad Oblast reveals a stable epidemiological gradient: natural foci in Leningrad Oblast sustain higher B. miyamotoi circulation in ticks and rodents, which translates into a two-fold higher exposure of the rural population. The findings highlight the need to include B. miyamotoi in regional tick-borne infection surveillance programs and to adopt differentiated risk assessment strategies for urban and rural settings. Full article

(This article belongs to the Special Issue Emerging Vector-Borne Diseases and Public Health Challenges)

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42 pages, 3543 KB

Open AccessReview

Emerging Perspectives on How Metallic Nanoparticles and Their Oxide Forms Interact with the Tumor Microenvironment

by Carlos Caro

Processes 2026, 14(12), 1977; https://doi.org/10.3390/pr14121977 (registering DOI) - 18 Jun 2026

Abstract

Cancer remains one of the most formidable health challenges worldwide. Extensive research has shown that tumor progression is not driven solely by malignant cells but is profoundly shaped by the tumor microenvironment (TME), which influences cancer initiation, immune evasion, and metastatic spread. Consequently, [...] Read more.

Cancer remains one of the most formidable health challenges worldwide. Extensive research has shown that tumor progression is not driven solely by malignant cells but is profoundly shaped by the tumor microenvironment (TME), which influences cancer initiation, immune evasion, and metastatic spread. Consequently, the TME has become an increasingly compelling therapeutic target. Nanotechnology has transformed cancer diagnostics and therapy, with metallic nanoparticles (mNPs) gaining particular attention due to their distinctive physicochemical properties and broad therapeutic potential. However, their interactions within the TME remain insufficiently understood, particularly with the non-cancerous cellular components, such as Cancer-Associated Fibroblasts (CAFs), Tumor-Associated Macrophages (TAMs), Dendritic Cells (DCs), Natural Killer (NK) cells, and T cells. Most existing reviews emphasize nanoparticle interactions with non-cellular TME components, such as the extracellular matrix, while far less attention has been given to their effects on cellular constituents (a gap this work specifically addresses). Although several molecular pathways through which mNPs modulate TME-resident cells have been identified, these likely represent only a small portion of the underlying mechanisms explored in this review. Progress in the field is further hindered by the limited availability of physiologically relevant experimental models; current in vitro and in vivo systems often fail to capture the complexity and dynamic heterogeneity of the TME. These limitations highlight the urgent need for more comprehensive and mechanistically grounded studies to validate the TME as a viable therapeutic target for nanoparticle-based cancer interventions. In particular, deeper insights into how mNPs influence immune regulation, stromal remodeling, and metabolic reprogramming within the TME will be essential for unlocking their full therapeutic potential in oncology. Full article

(This article belongs to the Special Issue Multiscale Modeling and Control of Biomedical Systems)

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Graphical abstract

17 pages, 7596 KB

Open AccessReview

From Collagen Colour to Collagen Biology: An Integrated Framework for Dermal Remodelling Assessment

by Francesco Marchetti, Matteo Basso, Giuseppe Colombo, Dissapong Panithaporn and Maurizio Cavallini

Cosmetics 2026, 13(3), 157; https://doi.org/10.3390/cosmetics13030157 (registering DOI) - 18 Jun 2026

Abstract

Age-related deterioration of the dermal extracellular matrix is driven primarily by fibroblast dysfunction, leading to loss of collagen integrity, elasticity, and structural support. In aesthetic dermatology, injectable and biostimulatory interventions increasingly target qualitative dermal remodelling, with collagen reorganisation widely adopted as a histological [...] Read more.

Age-related deterioration of the dermal extracellular matrix is driven primarily by fibroblast dysfunction, leading to loss of collagen integrity, elasticity, and structural support. In aesthetic dermatology, injectable and biostimulatory interventions increasingly target qualitative dermal remodelling, with collagen reorganisation widely adopted as a histological endpoint. Picrosirius red (PSR) staining under polarised light remains the most frequently used method for visualising collagen architecture; however, its birefringence colour patterns are often misinterpreted as proxies for collagen subtype shifts, particularly between types I and III. This conceptual review examines the methodological basis of such interpretations. We summarise the biological roles of major dermal collagens and compare current histochemical, immunohistochemical, ultrastructural and molecular methods for collagen assessment. We propose an interpretative framework that separates architectural collagen remodelling from molecular collagen synthesis and addresses the temporal dissociation between early fibre reorganisation and later subtype-specific expression as a plausible explanation for between-study discrepancies. Practical guidance is provided to support responsible interpretation and reporting of PSR-based collagen analyses. PSR is best regarded as a complementary tool for assessing collagen architecture rather than a definitive method for collagen subtype identification. Full article

(This article belongs to the Section Cosmetic Dermatology)

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16 pages, 782 KB

Open AccessArticle

A Comprehensive Analysis of the Agreement and Performance of Variant Annotation Programs in Equine Genomes

by Jillian L. Marlowe, Lauren Hughes, Eric Barrey, Tosso Leeb, Rebecca Bellone, Molly E. McCue and Sian Durward-Akhurst

Genes 2026, 17(6), 704; https://doi.org/10.3390/genes17060704 (registering DOI) - 18 Jun 2026

Abstract

Background/Objectives: Advances in whole-genome sequencing (WGS) technology have led to the widespread adoption of WGS for investigating genetic diseases and traits in domestic animals. This has created a need for improved methods for prioritizing candidate causal variants. One way variants are prioritized is [...] Read more.

Background/Objectives: Advances in whole-genome sequencing (WGS) technology have led to the widespread adoption of WGS for investigating genetic diseases and traits in domestic animals. This has created a need for improved methods for prioritizing candidate causal variants. One way variants are prioritized is using variant annotators that predict variant effects based on their proximity to genomic features and effect on amino acid sequence. However, validation of variant annotators for domestic animal genomes is lacking. Methods: In this study, we calculated the agreement of three popular variant annotators, Ensembl Variant Effect Predictor (Ensembl-VEP), SnpEff, and ANNOVAR, across >58 million variants identified in 1065 horse genomes. Results: Comparisons showed that agreement across all three variant annotators was >90% when terminology was standardized. Terminology standardization was the most important factor affecting agreement, as agreement dropped to 0–67% when terminology was not standardized across variant annotators. Genomic context was also a major factor, as exonic, and specifically loss-of-function, variants showed lower agreement rates than intergenic variants. In addition to annotation agreement, differences in computational resource requirements were identified. ANNOVAR required ~28× more memory and ~1.5× more time than the next best tool. Conclusions: These results demonstrate that tool selection for annotating variants should not be based on a single metric; rather, a study’s needs and available computational resources should be considered when selecting the appropriate variant annotators(s) along with the standardization of terminology across annotators. These findings are a resource for guiding decisions on the use of variant annotators in domestic animals and suggest areas for improvement in the standardization of variant prioritization. Full article

(This article belongs to the Special Issue Livestock Germplasm Resources, Genetics, and Breeding)

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22 pages, 25046 KB

Open AccessArticle

Improving the Performance of Low-Carbon Ultra-High-Performance Concrete Through the Incorporation of Recycled Coarse Aggregate

by Yongquan Zhang, Xinyue Hao, Weimin Guo, Chengzhe Song, Fan Yang and Meiqi Cao

Materials 2026, 19(12), 2621; https://doi.org/10.3390/ma19122621 (registering DOI) - 18 Jun 2026

Abstract

Supplementary cementitious materials and aeolian sand have been used to produce low-carbon ultra-high-performance concrete (UHPC) due to their beneficial effects on the reduction in production cost and carbon emissions. However, low-carbon UHPC still faces some drawbacks, such as lowered mechanical properties, large shrinkage, [...] Read more.

Supplementary cementitious materials and aeolian sand have been used to produce low-carbon ultra-high-performance concrete (UHPC) due to their beneficial effects on the reduction in production cost and carbon emissions. However, low-carbon UHPC still faces some drawbacks, such as lowered mechanical properties, large shrinkage, and a tendency for cracking. This study proposed an approach to improve the performance of low-carbon UHPC by incorporating recycled coarse aggregate. The effects of recycled coarse aggregate type, particle size, and content on the workability and mechanical properties of low-carbon UHPC were investigated. Moreover, the internal relative humidity and volume stability of UHPC containing recycled coarse aggregate was also explored. At last, the hydration products and microstructure of UHPC was analyzed to shed light on the underlying mechanisms for the improved performance. Full article

(This article belongs to the Special Issue High-Performance Concrete: Synergies Between Material Innovation and Structural Health Monitoring)

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18 pages, 3436 KB

Open AccessArticle

A Difference Equation Matrix Model Predictive Control Approach Applied to a Distillation Column

by Basil Mohammed Al-Hadithi, Javier Blanco Rico and Agustín Jiménez

Actuators 2026, 15(6), 347; https://doi.org/10.3390/act15060347 (registering DOI) - 18 Jun 2026

Abstract

The Difference Equation Matrix Model (DEMM) is presented as an input–output Model Predictive Control (MPC) formulation derived from discrete difference equations. The proposed approach is compared with the widely used Dynamic Matrix Control (DMC) strategy from a structural perspective, highlighting differences in model [...] Read more.

The Difference Equation Matrix Model (DEMM) is presented as an input–output Model Predictive Control (MPC) formulation derived from discrete difference equations. The proposed approach is compared with the widely used Dynamic Matrix Control (DMC) strategy from a structural perspective, highlighting differences in model parameterization, identification requirements, and matrix dimensions. The analysis indicates that DEMM provides a more compact model representation than the DMC formulation considered in this work while preserving the predictive-control framework. Furthermore, the DEMM strategy is applied to a binary distillation column, a multivariable nonlinear process, to illustrate its implementation and closed-loop behavior under disturbance, noise, and setpoint-change scenarios. Simulation results demonstrate satisfactory disturbance-rejection and tracking performance for the considered operating conditions. Full article

(This article belongs to the Special Issue Analysis and Design of Linear/Nonlinear Control System—2nd Edition)

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15 pages, 2917 KB

Open AccessArticle

Experimenting with Catalytic Stacks for Ortho-Parahydrogen Conversion in a Thermoacoustic Standing-Wave Engine

by Matthew Shenton, Nathan Jorgensen, Konstantin Matveev and Jacob Leachman

Cryo 2026, 2(2), 7; https://doi.org/10.3390/cryo2020007 (registering DOI) - 18 Jun 2026

Abstract

Thermoacoustic oscillations are excited sound waves in systems with large temperature gradients. Thermoacoustic engines and refrigerators can be constructed using porous materials to enhance the acoustic power produced and facilitate heat pumping for refrigeration. Porous materials can also be utilized as catalytic beds [...] Read more.

Thermoacoustic oscillations are excited sound waves in systems with large temperature gradients. Thermoacoustic engines and refrigerators can be constructed using porous materials to enhance the acoustic power produced and facilitate heat pumping for refrigeration. Porous materials can also be utilized as catalytic beds to convert between the two spin-isomers of hydrogen: orthohydrogen and parahydrogen. The conversion between ortho- and parahydrogen is either endothermic or exothermic, and the composition of the isomers manipulates the heat capacity of the fluid. This study experimentally investigates ortho-parahydrogen conversion in a thermoacoustic standing-wave engine with different oxidized catalytic materials. Recorded experimental measurements include the onset temperature ratio, acoustic pressure amplitude, and frequency of the thermoacoustic engine. The results depict a relationship between the oxidized materials and the acoustic amplitude. All oxidized materials promoted an increase in acoustic amplitude versus the pure metallic components. Steady-flow conversion was measured for brass oxide and iron oxide pellets; however, no conversion was detected for aluminum oxide or copper oxide pellets. The initial datapoints provide evidence that future cryogenic hydrogen thermoacoustic devices will need to account for the spin isomer conversion inside the stack. New flow-through regenerating liquefiers can also be constructed, which convert orthohydrogen to parahydrogen during liquefaction. Full article

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15 pages, 1655 KB

Open AccessArticle

Time-Delay Signature Suppressed Broadband Chaos for Dual-Polarization Bidirectional Chaotic Communication with Synchronized VCSELs

by Xingyu Huang, Zhuqiang Zhong, Jianjun Chen, Yipeng Zhu, Jinzhi Xu, Haiyang Yang, Chuanyi Tao and Yanhua Hong

Photonics 2026, 13(6), 592; https://doi.org/10.3390/photonics13060592 (registering DOI) - 18 Jun 2026

Abstract

We propose a time-delay signature suppressed broadband chaotic (TSBC) carrier generation scheme and theoretically investigate its performance in a dual-polarization bidirectional chaotic communication system based on synchronized vertical-cavity surface-emitting lasers (VCSELs). The TSBC scheme is implemented by combining fiber Bragg grating (FBG) feedback [...] Read more.

We propose a time-delay signature suppressed broadband chaotic (TSBC) carrier generation scheme and theoretically investigate its performance in a dual-polarization bidirectional chaotic communication system based on synchronized vertical-cavity surface-emitting lasers (VCSELs). The TSBC scheme is implemented by combining fiber Bragg grating (FBG) feedback with an external electro-optic (EO) phase modulation loop to introduce synergistic nonlinear perturbations. The results demonstrate that the proposed TSBC scheme effectively suppresses the time-delay signature (TDS) to less than 0.03 while significantly enhancing the chaotic carrier bandwidth to over 23 GHz for each polarization channel. Meanwhile, high-quality chaotic synchronization can be achieved with laser parameter mismatches of approximately 30%. Finally, an aggregated 46 Gbit/s dual-polarization bidirectional chaotic transmission is demonstrated, which confirms the effectiveness and the potential of the TSBC dual-polarization bidirectional scheme for secure optical communication applications. Full article

(This article belongs to the Special Issue Recent Advances in Optical Communication and Networks)

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15 pages, 4294 KB

Open AccessArticle

Comprehensive Analysis of the Electrical–Magneto–Mechanical Coupled Characteristics of AC Electromagnetic Actuators: A Case Study of Three-Phase AC Contactors

by Yubin He, Wanbin Ren, Zhihao Gu and Chao Zhang

Actuators 2026, 15(6), 346; https://doi.org/10.3390/act15060346 (registering DOI) - 18 Jun 2026

Abstract

The motion of AC electromagnetic actuators exhibits complex electrical–magneto–mechanical coupling characteristics. A three-phase AC contactor is taken as the typical research object in this paper. Using the finite-element method (FEM) and mesh deformation technique, the commercial software COMSOL Multiphysics is adopted to analyze [...] Read more.

The motion of AC electromagnetic actuators exhibits complex electrical–magneto–mechanical coupling characteristics. A three-phase AC contactor is taken as the typical research object in this paper. Using the finite-element method (FEM) and mesh deformation technique, the commercial software COMSOL Multiphysics is adopted to analyze its static electromagnetic characteristics, together with the operational coil current response and movable core displacement. In addition, the static correlation between the magnetic force, air gap, and time-varying magnetic force curves in the movement process are obtained. An experimental platform is established to measure the magnetic force of electromagnetic actuators. The experiment results demonstrate the feasibility of the proposed simulation method. The normalized root mean square errors between simulated and measured static magnetic forces are below 8% under all tested coil voltages. Furthermore, the effect of coil voltage phase angle on dynamic operational characteristics is thoroughly investigated. Combined with the closing time and final velocity of the movable core, the recommended operating window and its corresponding phase angle are determined. Full article

(This article belongs to the Section Control Systems)

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24 pages, 6049 KB

Open AccessArticle

Modified Decisional Conflict Scale for Primary Caregivers in Long-Term Care Facilities: Psychometric Validation Using Structural Equation Modeling

by Pai-Yueh Chen, Ying-Hua Chao, Yao-Ching Huang, Shi-Hao Huang, Ren-Jei Chung, Pi-Ching Yu, Bing-Long Wang, Hsiu-Ju Chang, Pi-Chen Chang, Shu-Min Huang and Chao-Hsi Huang

Healthcare 2026, 14(12), 1754; https://doi.org/10.3390/healthcare14121754 (registering DOI) - 18 Jun 2026

Abstract

Background: Caregivers of long-term care (LTC) residents often face decisional conflict during unplanned hospitalization decisions. This study aimed to adapt and psychometrically validate a modified Decisional Conflict Scale (DCS) for primary family caregivers. Methods: A cross-sectional survey was conducted among 205 caregivers in [...] Read more.

Background: Caregivers of long-term care (LTC) residents often face decisional conflict during unplanned hospitalization decisions. This study aimed to adapt and psychometrically validate a modified Decisional Conflict Scale (DCS) for primary family caregivers. Methods: A cross-sectional survey was conducted among 205 caregivers in 20 LTC facilities. Exploratory and confirmatory factor analyses (EFA/CFA) were performed on randomly split subsamples, and structural equation modeling (SEM) examined associations among Decision Antecedents, Decision-Making Process, and Decisional Conflict. Bollen–Stine bootstrap procedures were applied to provide robust estimates under slight deviations from multivariate normality. Given the cross-sectional design and single-sample nature of this study, the SEM findings should be interpreted as theory-informed associations rather than causal effects. Longitudinal or intervention-based studies are needed to establish temporal ordering and determine whether improvements in caregiver readiness and decision-making processes lead to subsequent reductions in decisional conflict. Results: The modified DCS demonstrated strong internal consistency and a single-factor structure (α = 0.98, factor loadings 0.83–0.90). SEM indicated that Decision Antecedents and Decision-Making Process were significantly associated with Decisional Conflict (R² = 0.68). The mediation analysis suggested that the Decision-Making Process partially mediated the relationship between Decision Antecedents and Decisional Conflict. Conclusions: The modified DCS appears to be a reliable and valid instrument for assessing decisional conflict among LTC caregivers. Findings highlight the importance of caregiver readiness, support, and communication in shaping decisional experiences. Given the cross-sectional design and single sample, results should be interpreted as associations rather than causal effects. Future research should replicate these findings in larger, diverse samples and explore short-form versions of the scale. Full article

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13 pages, 5744 KB

Open AccessArticle

Mortality Burden and Years of Life Lost Attributable to Air Pollution in Liguria, Italy: A Health Impact Assessment

by Sebastiano La Maestra, Francesco D’Agostini and Linda Ferrea

J. Xenobiot. 2026, 16(3), 114; https://doi.org/10.3390/jox16030114 (registering DOI) - 18 Jun 2026

Abstract

Air pollution is a major environmental determinant of premature mortality and population health burden. Liguria represents a vulnerable Mediterranean region due to intense urbanisation, port-related emissions, complex topography and an ageing population. This study quantified the mortality burden and Years of Life Lost [...] Read more.

Air pollution is a major environmental determinant of premature mortality and population health burden. Liguria represents a vulnerable Mediterranean region due to intense urbanisation, port-related emissions, complex topography and an ageing population. This study quantified the mortality burden and Years of Life Lost (YLL) attributable to long-term exposure to PM_2.5, NO₂ and O₃ in Liguria (Italy), and estimated the potentially avoidable burden under WHO guideline scenarios. A Health Impact Assessment (HIA) was conducted using ARPAL air quality data and ISTAT mortality data for the population aged ≥30 years during 2022–2024. Relative risks were derived from the European ELAPSE project and WHO meta-analyses. Attributable mortality was estimated using a log-linear Health Impact Function, while YLL were calculated using regional life tables and normalised per 100,000 inhabitants. PM_2.5 was the main contributor to air pollution-related mortality, accounting for 1333 attributable deaths in 2022. Corresponding YLL ranged from 755 to 1012 per 100,000 inhabitants over the study period. NO₂ showed a relevant but secondary contribution, while O₃ effects were smaller and more uncertain. WHO guideline scenarios indicated a substantial potentially avoidable burden of deaths and YLL. These findings support targeted environmental and public health interventions in highly urbanised coastal regions. Full article

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30 pages, 18112 KB

Open AccessArticle

Strain-Based Experimental Investigation of Load Transfer and Infill–Frame Interaction in Low-Strength RC Frames Under Cyclic Loading

by Nisar Ali Khan, Angelo Aloisio, Raihan Rahmat Rabi, Syed Saqib Mehboob and Giorgio Monti

Appl. Sci. 2026, 16(12), 6164; https://doi.org/10.3390/app16126164 (registering DOI) - 18 Jun 2026

Abstract

Reinforced concrete (RC) infilled frames are widely used structural systems; however, seismic design provisions often idealize masonry infill as non-structural, leading to uncertainty in performance assessment. This study experimentally and numerically investigates the role of unreinforced masonry infill in RC frames, focusing on [...] Read more.

Reinforced concrete (RC) infilled frames are widely used structural systems; however, seismic design provisions often idealize masonry infill as non-structural, leading to uncertainty in performance assessment. This study experimentally and numerically investigates the role of unreinforced masonry infill in RC frames, focusing on load-transfer mechanisms, strain evolution, and energy redistribution. Two 2/3-scale single-bay, single-storey RC frames (bare and fully infilled) were tested under constant axial load and quasi-static reversed cyclic lateral loading. Reinforcement strain gauges were used to capture local deformation demands, and a nonlinear macro-model was developed and validated against experimental results. Results show that the presence of masonry infill significantly increases ultimate strength, initial stiffness, and energy dissipation capacity, in comparatively more brittle post-peak cyclic behavior and accelerated stiffness degradation that leads to more abrupt post-peak degradation. Strain measurements provide clear evidence of a staged interaction mechanism: at low drift levels, the infill governs lateral resistance through diagonal compression strut action, limiting reinforcement demand in the frame; with increasing drift, progressive cracking and crushing of the infill promote a gradual transfer of forces to the RC frame, reflected by increasing reinforcement strains and stiffness degradation. At higher drift levels, the system transitions to frame-dominated behavior with localized strain concentration and shear failure at column bases or joints. These findings demonstrate that infill significantly modifies structural response and highlight the importance of incorporating strain-based mechanisms in the seismic assessment of infilled RC frames. Full article

(This article belongs to the Special Issue Advanced Structural Analysis for Earthquake-Resistant Design of Buildings: 2nd Edition)

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22 pages, 2506 KB

Open AccessArticle

Clinical and Inflammatory Predictors of Neurocognitive Decline in Long COVID: A Two-Year Longitudinal Study with Propensity Score Matching

by Iulia Elena Diaconu, Maria Ioana Onofrei, Andrei Vâță, Florin Manuel Roșu, Emilian Bogdan Ignat, Iulian Dan Cuciureanu, Mihnea Eudoxiu Hurmuzache and Mihaela Cătălina Luca

Medicina 2026, 62(6), 1180; https://doi.org/10.3390/medicina62061180 (registering DOI) - 18 Jun 2026

Abstract

Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and [...] Read more.

Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819–5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191–2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431–2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65–14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412–6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353–19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention. Full article

(This article belongs to the Section Infectious Disease)

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22 pages, 2619 KB

Open AccessArticle

Item Analysis of a High-Stakes Placement Assessment for Junior High School Students with Intellectual Disabilities

by Pen-Chiang Chao, Miwako Hoshi, Yu-Chi Chou, Shan-Ken Chien and Chia-Yi Chu

Educ. Sci. 2026, 16(6), 967; https://doi.org/10.3390/educsci16060967 (registering DOI) - 18 Jun 2026

Abstract

This study examines the psychometric functioning of the Basic Learning Ability Assessment (BLAA), a high-stakes placement assessment used in Taiwan’s Adaptive Guidance Placement System (AGPS) for junior high school students with intellectual disabilities (IDs). The sample comprised 203 ninth-grade students with ID from [...] Read more.

This study examines the psychometric functioning of the Basic Learning Ability Assessment (BLAA), a high-stakes placement assessment used in Taiwan’s Adaptive Guidance Placement System (AGPS) for junior high school students with intellectual disabilities (IDs). The sample comprised 203 ninth-grade students with ID from 47 public junior high schools in Taiwan, all of whom completed three operational multiple-choice forms of the BLAA. Using classical test theory (CTT), we examined item difficulty using proportion-correct indices, item discrimination using upper–lower group discrimination indices, distractor functioning by comparing response patterns between higher- and lower-performing examinees, and internal consistency reliability using the Kuder–Richardson Formula 20 (KR-20). The results show that most items fell within the average-to-easy range and demonstrated acceptable to strong discrimination. Distractor functioning was generally satisfactory, with most items containing no nonfunctioning distractors. KR-20 coefficients ranged from 0.904 to 0.926, indicating high internal consistency within each form. Functional Language and Social Adaptation showed relatively stable psychometric patterns, whereas Mathematical Skills displayed greater variability in item difficulty, discrimination, and distractor functioning. Overall, the findings provide initial CTT-based internal psychometric evidence regarding the item functioning and form-level reliability of the BLAA, while highlighting the need for ongoing item refinement, particularly in the Mathematical Skills domain. Full article

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17 pages, 2235 KB

Open AccessSystematic Review

Diagnostic Accuracy of Urine and Vaginal Self-Sampling for Detection of High-Risk Human Papillomavirus: A Systematic Review and Meta-Analysis

by Altynshash Rakhat and Gulzhanat Aimagambetova

Viruses 2026, 18(6), 681; https://doi.org/10.3390/v18060681 (registering DOI) - 18 Jun 2026

Abstract

Cervical cancer remains a major public health challenge, particularly in low- and middle-income countries. The primary cause of cervical cancer is high-risk human papillomavirus (HPV), and screening using physician-collected samples is complicated by stigma, inconvenience, and access. There are non-invasive alternatives to the [...] Read more.

Cervical cancer remains a major public health challenge, particularly in low- and middle-income countries. The primary cause of cervical cancer is high-risk human papillomavirus (HPV), and screening using physician-collected samples is complicated by stigma, inconvenience, and access. There are non-invasive alternatives to the physician-collected samples, including self-sampling methods such as first-void urine and vaginal swabs. This systematic review and meta-analysis evaluated and compared the diagnostic accuracy of vaginal and urine self-sample methods for detecting high-risk HPV. PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies published between January 2015 and October 2025. Bivariate random-effects models and HSROC models were used to estimate pooled sensitivity and specificity results compared with clinician-collected samples for CIN2+. Meta-regression assessed sources of heterogeneity. Twenty-two studies involving over 9000 participants were included. Vaginal self-sampling showed a pooled sensitivity of 91.3% and a specificity of 86.9%, while urine self-sampling showed 86.9% sensitivity and 79.5% specificity. Vaginal swabs demonstrated higher sensitivity in head-to-head comparisons. DNA-based PCR assays showed higher sensitivity than mRNA-based tests, and room-temperature storage decreased urine sample sensitivity. Both methods are effective for high-risk HPV detection. Vaginal self-sampling showed superior performance, while urine self-sampling remains a valuable non-invasive option for under-screened populations. Full article

(This article belongs to the Special Issue Oncogenic Infections and Cancer: Clinical Insights and Emerging Therapeutics)

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16 pages, 4790 KB

Open AccessArticle

Blue Honeysuckle (Lonicera caerulea L.) Polyphenol Extract Inhibits α-Glucosidase Activity and Modulates Glucose Transport in Caco-2 Cells

by Fengfeng Li, Yao Wang, Huifang Shen, Xinting Shen, Fei Wang, Rui Zhao, Zhebin Li, Bo Li, Ye Zhou and Xinmiao Yao

Molecules 2026, 31(12), 2146; https://doi.org/10.3390/molecules31122146 (registering DOI) - 18 Jun 2026

Abstract

Blue honeysuckle (Lonicera caerulea L.) is a polyphenol-rich berry increasingly recognized as a functional food ingredient for postprandial glycemic management. However, it remains unclear whether its polyphenols can modulate intestinal glucose transport in addition to inhibiting carbohydrate-digesting enzymes. In this study, blue [...] Read more.

Blue honeysuckle (Lonicera caerulea L.) is a polyphenol-rich berry increasingly recognized as a functional food ingredient for postprandial glycemic management. However, it remains unclear whether its polyphenols can modulate intestinal glucose transport in addition to inhibiting carbohydrate-digesting enzymes. In this study, blue honeysuckle polyphenol extract (BHPE) was characterized by UPLC-QTOF-MS/MS, and its effects on α-glucosidase activity and intestinal glucose transport were evaluated using enzyme kinetics, fluorescence quenching, molecular docking, and differentiated Caco-2 monolayers. A total of 24 phenolic compounds were tentatively identified, with anthocyanins and chlorogenic acid derivatives as the major constituents. BHPE exhibited a mixed-type, static-quenching inhibition of α-glucosidase (IC₅₀ = 75.05 μg/mL). Furthermore, molecular docking revealed that key constituents, including cyanidin-3-O-glucoside, chlorogenic acid, and proanthocyanidin B1, bind the enzyme via hydrogen bonding and hydrophobic interactions. In Caco-2 cell monolayers, BHPE reduced glucose transport by up to 51.56% under simulated postprandial conditions and coordinately downregulated SGLT1 and GLUT2 mRNA expression to 0.58- and 0.51-fold, respectively. These findings extend the bioactivity profile of blue honeysuckle polyphenols from enzyme-level inhibition to functional regulation at the intestinal epithelial barrier, highlighting their potential as multi-target natural ingredients for the attenuation of postprandial hyperglycemia. Full article

(This article belongs to the Special Issue Bioactive Food Compounds and Their Health Benefits)

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Graphical abstract

33 pages, 4450 KB

Open AccessArticle

Attention-Enhanced Hybrid CNN–ViT Framework for Genus-Level Classification of Selected Macrofungi from Basidiospore Micrographs

by Şuheda Aldemir Terman, Mustafa Emre Akçay, Ebubekir Seyyarer, Faruk Ayata and İsmail Acar

Appl. Sci. 2026, 16(12), 6167; https://doi.org/10.3390/app16126167 (registering DOI) - 18 Jun 2026

Abstract

The development of rapid and reproducible image analysis approaches that support genus-level pre-classification of macrofungi is important for taxonomic pre-evaluation and controlled microscopic data analysis. In this study, an advanced deep learning-based approach, namely the Attention-Enhanced Hybrid CNN–ViT Framework, was rigorously evaluated for [...] Read more.

The development of rapid and reproducible image analysis approaches that support genus-level pre-classification of macrofungi is important for taxonomic pre-evaluation and controlled microscopic data analysis. In this study, an advanced deep learning-based approach, namely the Attention-Enhanced Hybrid CNN–ViT Framework, was rigorously evaluated for genus-level classification, using basidiospore micrographs of five carefully selected macrofungal genera. The proposed approach integrates the ability of convolutional neural networks to identify local texture and contour patterns with the global context-modelling capability of Vision Transformer structures. The objective is to enhance the extraction of distinctive representations from microscopic spore images through feature fusion and attention mechanisms. A series of experiments was conducted on a curated dataset consisting of light microscopy images of the genera Agaricus, Hebeloma, Inocybe, Amanita, and Russula. The models were compared using a range of evaluation metrics, including accuracy, F1-score, MCC, ROC-AUC, and PR-AUC. The results showed that the InceptionV3 + ViT-B16 + Fusion configuration was the most successful hybrid model, achieving an accuracy of 0.9213 ± 0.0182, an F1-score of 0.9212 ± 0.0179, a Matthews correlation coefficient (MCC) of 0.9040 ± 0.0222, a receiver operating characteristic (ROC)-area under the curve (AUC) of 0.9896 ± 0.0069, and a precision-recall (PR)-AUC of 0.9684 ± 0.0192, respectively. The present findings demonstrate that basidiospore images can carry distinctive visual information for genus-level automated classification under controlled conditions. However, it is important to note that these results should not be interpreted as claims of species-level identification or field generalisability. This is due to the use of a single microscope-camera system, a single preparation protocol, and the absence of an independent external test set. The present study demonstrates that deep learning-based microscopic image analysis can be evaluated as a preliminary classification tool in macrofungal taxonomy. It also shows that such tools can provide a foundation for future work supported by specimen-level validation, external test sets, and different imaging protocols. Full article

(This article belongs to the Section Applied Microbiology)

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11 pages, 578 KB

Open AccessBrief Report

Comparison of Heart Rate Variability Between Sexes: Impact of a Physically Active Lifestyle

by Reberth Magalhães Da Silva, Ariane Viana, Fernanda Monma, Fernando Alves Santa Rosa, José Robertto Zaffalon, Jr. and Kátia De Angelis

Int. J. Environ. Res. Public Health 2026, 23(6), 809; https://doi.org/10.3390/ijerph23060809 (registering DOI) - 18 Jun 2026

Abstract

Sex differences and lifestyle factors such as physical activity play an important role in cardiovascular autonomic regulation. Heart rate variability (HRV) is a widely used marker of cardiac autonomic modulation and cardiovascular health. However, the combined influence of sex and physical activity levels [...] Read more.

Sex differences and lifestyle factors such as physical activity play an important role in cardiovascular autonomic regulation. Heart rate variability (HRV) is a widely used marker of cardiac autonomic modulation and cardiovascular health. However, the combined influence of sex and physical activity levels on HRV in young, healthy adults has not been sufficiently explored. Therefore, this study investigated the effects of sex and a physically active lifestyle on HRV in men and women. A cross-sectional study was conducted on a cohort of young, healthy adults aged 18–30 and categorized into four groups based on: physically active men (AM; n = 37), sedentary men (SM; n = 44), and physically active women (AW; n = 31) and sedentary women (SW; n = 40). Regarding the impact of lifestyle, the AM group exhibited 41% higher total variance (VAR-RR) and 34% higher RMSSD (a parasympathetic index) than the SM group. The AW exhibited 74% and 78% higher VAR-RR and RMSSD, respectively, compared to the SW. Furthermore, the physically active groups (AM and AW) displayed a 75% and 50% lower LF/HF ratio, respectively, compared to their sedentary counterparts. Interestingly, the LF/HF ratio was 66% higher, and the RMSSD was 20% lower in the AM group than in the AW group. HRV indices demonstrated large to very large effect sizes. In conclusion, these findings demonstrate significantly advantage in cardiac autonomic modulation among physically active individuals and women. Together, these results reinforce the roles of female sex and an active lifestyle as important protective factors for cardiovascular health. Full article

(This article belongs to the Special Issue Health Effects of Physical Activity and Exercise in People at Risk for Cardiovascular Diseases)

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18 pages, 3752 KB

Open AccessArticle

Study of Molding–Regeneration Process of Powdered Spent Activated Carbon: Response Surface Methodology Optimization and Regeneration Mechanism

by Jinxuan Si, Hongyue Zhu and Zequan Zeng

Processes 2026, 14(12), 1978; https://doi.org/10.3390/pr14121978 (registering DOI) - 18 Jun 2026

Abstract

A regeneration process for powdered spent activated carbon was developed through binder-assisted forming and thermal regeneration, and the process parameters were optimized by using response surface methodology (RSM). The effects of calcination time, calcination temperature, and binder ratio on the iodine adsorption value [...] Read more.

A regeneration process for powdered spent activated carbon was developed through binder-assisted forming and thermal regeneration, and the process parameters were optimized by using response surface methodology (RSM). The effects of calcination time, calcination temperature, and binder ratio on the iodine adsorption value of spent activated carbon were investigated by using a Central Composite Design. The quadratic regression model exhibited high accuracy and statistical significance (R² = 0.9934, p < 0.0001), indicating good agreement between the predicted and experimental results. The optimal regeneration conditions were determined as a calcination time of 39.2 min, a calcination temperature of 848 °C, and a binder ratio of 10.15%. Under the optimized conditions, the VOCs (dichloromethane) adsorption capacity increased sharply from 9.1 mg/g to 108.2 mg/g. Characterization results showed that the regeneration process effectively restored the pore structure and improved the surface properties of the activated carbon. Thermogravimetric analysis demonstrated the effective removal of adsorbed pollutants. XPS analysis revealed a decrease in oxygen-containing functional groups, particularly –COOH groups, accompanied by an increase in C=O content, while the C–O groups changed only slightly. These structural and surface modifications contributed to the recovery of adsorption performance and provide guidance for the regeneration of powdered spent activated carbon. Full article

(This article belongs to the Section Chemical Processes and Systems)

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13 pages, 1172 KB

Open AccessReview

Dysbiosis and Immune Crosstalk in Experimental Diabetic Periodontitis: A Systemic Review and Meta-Analysis of Preclinical Murine Studies

by Amani M. Harrandah

Int. J. Mol. Sci. 2026, 27(12), 5499; https://doi.org/10.3390/ijms27125499 (registering DOI) - 18 Jun 2026

Abstract

Diabetes mellitus (DM) fundamentally disrupts the oral microbiome, initiating a dysbiotic shift that drives progressive periodontal tissue breakdown. This transition is mediated by complex, bidirectional immune crosstalk, primarily centering on the upregulation of the Th17/Interleukin-17 (IL-17) inflammatory pathway. This systematic review and meta-analysis [...] Read more.

Diabetes mellitus (DM) fundamentally disrupts the oral microbiome, initiating a dysbiotic shift that drives progressive periodontal tissue breakdown. This transition is mediated by complex, bidirectional immune crosstalk, primarily centering on the upregulation of the Th17/Interleukin-17 (IL-17) inflammatory pathway. This systematic review and meta-analysis quantified the specific impact of this diabetic microbiota on immune activation and periodontal destruction. A comprehensive search of PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library was conducted for studies published up to 2026. Eligible studies included assessing oral/salivary microbiome shifts and their localized or systemic immunological consequences in diabetic periodontitis. A random-effects meta-analysis synthesized standardized mean differences (Hedges’ g) to evaluate the magnitude of these effects. Quantitative synthesis of preclinical data (four studies yielding eight discrete comparisons) revealed that exposure to a diabetic/dysbiotic microbiota significantly increased overall immune activation and periodontal inflammation relative to eubiotic controls (pooled Hedges’ g = 3.73, 95% CI 2.96–4.51). Subgroup analyses confirmed profound, statistically significant effects specifically on the Th17/IL-17 axis (g = 4.03) and periodontal bone destruction pathways (g = 3.37). Preclinical murine data suggests diabetes-associated oral dysbiosis may contribute to periodontal destruction by upregulating the Th17/IL-17 immune axis. However, direct extrapolation to humans is restricted, necessitating further clinical studies to validate these findings. Full article

(This article belongs to the Special Issue The Role of Gut Microbiome Regulation in Immunity and Inflammation)

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21 pages, 1743 KB

Open AccessReview

Cellular Models and Functional Assays for Assessing CFTR Function: A Comprehensive Review

by Margarita Lopatina, Anna Demchenko and Svetlana Smirnikhina

Int. J. Mol. Sci. 2026, 27(12), 5497; https://doi.org/10.3390/ijms27125497 (registering DOI) - 18 Jun 2026

Abstract

Cystic fibrosis (CF) is a genetic disorder caused by dysfunction of the CFTR chloride ion channel. Progress in molecular understanding and therapy development relies on advanced cellular models and robust assays for evaluating CFTR function. This review traces the evolution of in vitro [...] Read more.

Cystic fibrosis (CF) is a genetic disorder caused by dysfunction of the CFTR chloride ion channel. Progress in molecular understanding and therapy development relies on advanced cellular models and robust assays for evaluating CFTR function. This review traces the evolution of in vitro models, from primary and immortalized cell lines to patient-specific induced pluripotent stem cells (iPSCs) and complex three-dimensional systems. These advanced models, including air-liquid interface (ALI) cultures, organoids, and microfluidic organ-on-a-chip platforms, enable recapitulation of tissue architecture, cellular heterogeneity, and key pathological features such as impaired mucociliary clearance and chronic inflammation. A critical component of CF research is the accurate functional assessment of CFTR activity. We compare established high-resolution techniques (patch-clamp, Ussing chamber) with high-throughput screening assays, including fluorescence quenching of halide-sensitive YFP assay and organoid swelling tests. The article provides a framework for choosing the most appropriate CFTR functional assay tailored to specific research goals. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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18 pages, 1751 KB

Open AccessArticle

Determinants of Rabies Post-Exposure Prophylaxis Compliance in Bangladesh: Informing Policy for Elimination by 2030

by Sumon Ghosh, Mohammad Nayeem Hasan, Sukanta Chowdhury, Narayan C. Paul, Waqas Ahmad, Jiangang Chen and Thankam S. Sunil

Trop. Med. Infect. Dis. 2026, 11(6), 165; https://doi.org/10.3390/tropicalmed11060165 (registering DOI) - 18 Jun 2026

Abstract

Rabies remains a preventable yet fatal zoonotic disease and a major public health concern in Bangladesh, which aims to eliminate dog-mediated human rabies by 2030. Despite free availability of post-exposure prophylaxis (PEP), adherence to the WHO-recommended PEP regimen remains low. This study assessed [...] Read more.

Rabies remains a preventable yet fatal zoonotic disease and a major public health concern in Bangladesh, which aims to eliminate dog-mediated human rabies by 2030. Despite free availability of post-exposure prophylaxis (PEP), adherence to the WHO-recommended PEP regimen remains low. This study assessed PEP compliance and identified determinants of regimen completion among animal-exposed patients. We conducted a hospital-based observational study using secondary data from 457 patients who initiated PEP at the National Rabies Prevention and Control Centre (NRPCC) in Dhaka, from February 2023 to July 2023. Sociodemographic, clinical, and exposure-related factors were analyzed to identify predictors of compliance. Only 17.1% of patients completed the full PEP regimen, including rabies immunoglobulin (RIG) administration for WHO Category III exposures where indicated. Higher adherence was observed among females, individuals aged ≥15 years, lower-income groups, and those residing within 10 km of the treatment center. Exposure-related factors including dog bites, multiple exposures, unprovoked incidents, and appropriate exposure care were also associated with improved compliance. Despite free access, PEP completion remains critically low. Targeted strategies, including decentralized PEP delivery, improved public awareness, and strengthened follow-up systems, are essential to improve adherence and support progress toward rabies elimination by 2030. Full article

(This article belongs to the Special Issue Recent Advances in Rabies Surveillance and Control)

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16 pages, 805 KB

Open AccessArticle

Effects of Caffeinated Chewing Gum on Psychophysiological Responses and Kinematic Profiles During Intermittent and Continuous Small-Sided Soccer Games in Young Male Players: A Randomized Crossover Trial

by Bulent Kilit, Ersan Arslan and Yusuf Soylu

Nutrients 2026, 18(12), 1962; https://doi.org/10.3390/nu18121962 (registering DOI) - 18 Jun 2026

Abstract

Background/Objectives: Caffeinated chewing gum is a practical, rapidly absorbed ergogenic aid increasingly used in team sports, yet its interaction with different small-sided soccer game (SSG) formats in young male players remains unclear. This study evaluated the effects of acute caffeinated (CAF) chewing [...] Read more.

Background/Objectives: Caffeinated chewing gum is a practical, rapidly absorbed ergogenic aid increasingly used in team sports, yet its interaction with different small-sided soccer game (SSG) formats in young male players remains unclear. This study evaluated the effects of acute caffeinated (CAF) chewing gum on psychophysiological responses and kinematic profiles during intermittent (INT) and continuous (CON) 3-a-side SSGs. Methods: Twenty-four young male soccer players (18.4 ± 0.5 years) completed four 3-a-side SSG sessions separated by 48 h in a randomized, double-blind, placebo (PLA)-controlled, crossover design (CAF-INT, PLA-INT, CAF-CON, PLA-CON). Participants chewed 300 mg of CAF or PLA gum for 5 min, with mastication completed 5 min before warm-up session. The heart rates and kinematic profiles were recorded during the SSGs, and the ratings of perceived exertion (RPE), exercise enjoyment scale (EES), and visual analogue scale (VAS) to perceived mental fatigue (MF) were assessed post-game. Results: Compared with the PLA, the CAF increased the heart rate responses (HR), EES, total distance (TD), player load (PL), acceleration (ACC), and distances covered in selected speed zones (from Z0 to Z5), while reducing the RPE and MF. Significant format × supplementation interactions indicated that CAF-induced changes in high-intensity kinematic outcomes (TD, PL, ACC, Z2–Z5) and HR responses (HR_mean, HR_max) were generally greater in INT, whereas CAF-induced increases in low-intensity running distances (Z0 and Z1) and %HR_max were more pronounced in the CON format (all p < 0.05 for the reported effects;

η_{p}^{2}

= 0.16–0.93 for CAF main effects [large effects]). The EES improvements were more pronounced in the CON format, whereas the MF and RPE reductions were more pronounced in the INT format. Conclusions: CAF chewing gum may be a practical acute strategy for modulating psychophysiological responses and kinematic profiles during SSGs, with the effects depending partly on the game format. Full article

(This article belongs to the Special Issue The Ergogenic Effects of Caffeine Intake in Sport)

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25 pages, 10945 KB

Open AccessArticle

Effects of Vitamin B6 and Folic Acid on Cardiometabolic Biomarkers and Cardiac Oxidative Stress in Homocysteine-Loaded Rats

by Dušan Todorović, Marija Stojanović, Slavica Mutavdžin Krneta, Jovana Jakovljević Uzelac, Nina Radisavljević, Kristina Gopčević, Ana Medić, Milica Labudović Borović, Jelena Rakočević, Sanja Stanković and Dragan Djuric

Biomedicines 2026, 14(6), 1373; https://doi.org/10.3390/biomedicines14061373 (registering DOI) - 18 Jun 2026

Abstract

Background/Objectives: Elevated homocysteine (Hcy) levels are associated with endothelial dysfunction, oxidative stress, and inflammation, contributing to cardiovascular disease development. The aim of this study was to examine the effects of vitamin B6 and folic acid on cardiometabolic biomarkers, cardiac oxidative stress, metabolic enzyme [...] Read more.

Background/Objectives: Elevated homocysteine (Hcy) levels are associated with endothelial dysfunction, oxidative stress, and inflammation, contributing to cardiovascular disease development. The aim of this study was to examine the effects of vitamin B6 and folic acid on cardiometabolic biomarkers, cardiac oxidative stress, metabolic enzyme activities and cardiovascular histomorphometric parameters in homocysteine-loaded rats. Methods: Male Wistar albino rats were divided into four groups (n = 10, per group): C—saline 0.2 mL/day s.c. + saline 0.5 mL i.p; H: Hcy 0.45 µmol/g b.w./day s.c. + saline 0.5 mL i.p; C-B6+FA—saline 0.2 mL/day s.c. + vitamin B6 (7 mg/kg b.w. i.p./day) and folic acid (FA) (5 mg/kg b.w. i.p./day); and H-B6+FA—Hcy (0.45 µmol/g b.w./day s.c.) + vitamin B6 (7 mg/kg b.w. i.p./day) and FA (5 mg/kg b.w. i.p./day). Substances were applied s.c. for 2 weeks and i.p for 4 weeks. Results: B6+FA supplementation significantly reduced serum Hcy and LDL concentrations and attenuated Hcy-associated increases in cardiac SOD activity and right ventricular wall thickness. However, B6+FA was associated with increased cardiac MDA levels. MDH activity increased mainly in non-Hcy-loaded supplemented rats, whereas LDH activity, the cardio-somatic index, and aortic histomorphometric parameters remained unchanged. Conclusions: Combined B6+FA supplementation may improve Hcy metabolism, the LDL profile, and selected cardiac structural/oxidative alterations, but its association with increased lipid peroxidation suggests complex redox effects requiring cautious interpretation. Full article

(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—5th Edition)

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