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Recent Articles  

35 pages, 11887 KB  
Review
CAR T-Cell Immunotherapy in Neuroautoimmune Diseases: Focus on the Central Nervous System
by Fotis Demetriou and Maria Anagnostouli
Biomedicines 2026, 14(2), 296; https://doi.org/10.3390/biomedicines14020296 (registering DOI) - 29 Jan 2026
Abstract
The treatment of central nervous system (CNS) autoimmune diseases has evolved from broad immunosuppression toward targeted disease-modifying therapies (DMTs). While current DMTs effectively control inflammatory activity in many patients, unmet needs remain, including persistent compartmentalised CNS pathology, limited tissue penetration, and the cumulative [...] Read more.
The treatment of central nervous system (CNS) autoimmune diseases has evolved from broad immunosuppression toward targeted disease-modifying therapies (DMTs). While current DMTs effectively control inflammatory activity in many patients, unmet needs remain, including persistent compartmentalised CNS pathology, limited tissue penetration, and the cumulative burden of chronic therapy. Chimeric antigen receptor (CAR) T-cell therapy represents a novel “living” immunotherapy capable of antigen-specific cellular depletion. Although currently approved only for B-cell malignancies, CAR T-cells are increasingly being explored in CNS autoimmunity leveraging their capacity for autonomous cytotoxicity and expected access to immune cells within protected CNS niches following a potentially single intervention. In this review, we examine CAR T-cells in the context of CNS-autoimmunity, we outline principles derived from oncologic applications, assess current DMTs, their limitations and side effects, and define parameters where CAR T-cells may offer added value. We discuss biological and practical requirements for broader clinical application, as currently they are investigated only for the very severe and refractory cases where all alternative treatments have failed. We further review the plasticity of CAR constructs, distinguishing clinically advanced platforms from early proof-of-concept approaches. Finally, we summarise clinical experience from 15 patients with CNS autoimmunity treated with CAR T-cells and review ongoing or planned trials that include such patients. We conclude that CAR T-cell therapy remains investigational for severe, treatment-refractory disease, with future applicability dependent on demonstrable efficacy, safety, cost, and feasibility beyond existing DMTs. Full article
(This article belongs to the Collection Feature Papers in Immunology and Immunotherapy)
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20 pages, 612 KB  
Article
Sexuality in the Elderly in Chile
by Jhonny Acevedo Ayala, Constanza Bartolucci Konga, Francisca Molero Rodríguez, Marcelo Vásquez León and Eliana Espinoza Alarcón
Sexes 2026, 7(1), 4; https://doi.org/10.3390/sexes7010004 (registering DOI) - 29 Jan 2026
Abstract
Population aging is a reality in Chile that affects the course of life, quality of life, and sexuality of older adults. The objective of this study is to identify the dimensions, characteristics, and underlying contents of sexuality in older adults participating in community-based [...] Read more.
Population aging is a reality in Chile that affects the course of life, quality of life, and sexuality of older adults. The objective of this study is to identify the dimensions, characteristics, and underlying contents of sexuality in older adults participating in community-based organizations in Chile. A qualitative study was conducted using grounded theory, based on ten focus groups with N of 85 participants aged 60 and over. Groups of women, men, and mixed groups were organized in the northern, central, and south-central zones of the country. The data were entered and analyzed using MAXQDA 2023 software. The results identified 10 dimensions and 42 sub-dimensions related to the sexuality of older adults. A structural educational deficit in the subject was identified, characterized by a lack of training for health care personnel and care gaps at the primary health care level, among other issues. It is concluded that sexuality in older adults is an emerging issue and a human right subject to social discrimination, with limitations to its full experience which must be studied and addressed to improve sexuality as part of changes in quality of life. Full article
(This article belongs to the Section Sexual Behavior and Attitudes)
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24 pages, 5506 KB  
Article
Complexity of Hydroclimatic Changes in the Mediterranean: Exploring Climate Drivers Using ERA5 Reanalysis
by Theano Iliopoulou, Marianna Lada, Christina-Ioanna Stavropoulou, Dimitra-Myrto Tourlaki, Nikos Tepetidis, Panayiotis Dimitriadis and Demetris Koutsoyiannis
Water 2026, 18(3), 331; https://doi.org/10.3390/w18030331 (registering DOI) - 29 Jan 2026
Abstract
The Mediterranean region has experienced pronounced hydroclimatic variability over recent decades, motivating a closer examination of the physical processes underlying these changes. This study analyzes ERA5 reanalysis data for 1950–2024 to investigate long-term trends and interrelations among temperature, precipitation, evaporation, wind, sensible heat, [...] Read more.
The Mediterranean region has experienced pronounced hydroclimatic variability over recent decades, motivating a closer examination of the physical processes underlying these changes. This study analyzes ERA5 reanalysis data for 1950–2024 to investigate long-term trends and interrelations among temperature, precipitation, evaporation, wind, sensible heat, and column water, distinguishing between land and sea domains and multiple atmospheric layers. Results show a strong warming signal in the lower troposphere, with temperatures increasing by 0.03 °C year−1 over land and 0.015 °C year−1 over sea, and near-stagnancy in the upper troposphere, which indicates a steepening lapse rate. Unlike temperature, evaporation shows no strong long-term increase: over sea, it rises only slightly, and over land, it declines modestly, with both weak tendencies dominated by strong interannual variability and consistent with declining winds. Over land, sensible heat flux increases, while over the sea, it decreases, revealing divergent energy-partition regimes. Precipitation exhibits no significant long-term change, suggesting that the atmosphere has become warmer and slightly moister but less effective in converting vapor into rainfall. Correlation analyses indicate that wind speed exerts a stronger control on evaporation and precipitation than temperature across the whole region. The Hurst–Kolmogorov stochastic framework further reveals persistent long-term variability in Mediterranean hydroclimatic processes, underscoring that the region’s climate behavior is shaped by dynamic and complex interactions rather than by temperature trends alone. Full article
(This article belongs to the Section Water and Climate Change)
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13 pages, 3113 KB  
Article
Meesmann Corneal Dystrophy with Epithelial Basement Membrane Abnormalities: Clinical and Genetic Analysis of Two Families with Novel and Known Mutations in KRT3 and KRT12
by Víctor Charoenrook, Raquel Larena, Álvaro Ferragut-Alegre, Alix De Faria, Rebeca Valero, Mònica Martí-Orpinell, Gemma Julio and Rafael I. Barraquer
Int. J. Mol. Sci. 2026, 27(3), 1326; https://doi.org/10.3390/ijms27031326 (registering DOI) - 29 Jan 2026
Abstract
This study describes the clinical and genetic features of Meesmann epithelial corneal dystrophy (MECD) in two unrelated families and reports new genotype–phenotype associations. Ten patients from a Lebanese family (n = 4) (Family 1) and a Spanish family (n = 6) [...] Read more.
This study describes the clinical and genetic features of Meesmann epithelial corneal dystrophy (MECD) in two unrelated families and reports new genotype–phenotype associations. Ten patients from a Lebanese family (n = 4) (Family 1) and a Spanish family (n = 6) (Family 2) underwent ophthalmologic evaluation, in vivo confocal microscopy (IVCM), anterior segment optical coherence tomography (AS-OCT) with epithelial thickness mapping (ET-map), and targeted next-generation sequencing (NGS) using a custom-designed 133-gene panel associated with anterior segment dystrophies. In Family 1, a novel homozygous KRT12 c.1181T>C (p.Leu394Pro) variant was identified in the symptomatic proband and his clinically asymptomatic brother, while both parents, who were first cousins, were heterozygous for this nucleotide variant. The proband also carried the heterozygous KRT3 c.250C>T (p.Arg84Trp) variant, which has been previously reported but, to our knowledge, has not been described in co-occurrence until now. In addition, the proband showed a complex phenotype with signs of MECD and epithelial basal membrane alterations consistent with epithelial basement membrane dystrophy (EBMD). In Family 2, four affected members carried the KRT3 c.1492G>A (p.Glu498Lys) variant in heterozygosity, which has been previously described. The elderly members affected showed typical signs of MECD and EBMD. To our knowledge, these concomitant alterations have not been previously described with genetical confirmation. In conclusion, this study provides the first evidence that the co-occurrence of variants in two Meesmann corneal dystrophy-associated genes (KRT3 and KRT12) can jointly account for the disease phenotype. We also highlight the association of MECD with EBMD in both families. Characterization using IVCM and AS-OCT ET-Map provides a deeper understanding of the morphological changes and phenotypic variability in MECD, confirming the utility of this multimodal imaging approach for diagnosis and management. Full article
(This article belongs to the Special Issue Integrated Approaches, Molecular Mechanism and Therapies in Ocular Surface Diseases)
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25 pages, 55049 KB  
Article
Reduced CHMP7 Expression Compromises Telomere Integrity in Mammalian Cells
by Romina Burla, Mattia La Torre, Klizia Maccaroni, Stefano Tacconi, Luciana Dini and Isabella Saggio
Cells 2026, 15(3), 256; https://doi.org/10.3390/cells15030256 (registering DOI) - 29 Jan 2026
Abstract
During open mitosis, reassembly of the nuclear envelope requires the coordinated recruitment of the ESCRT machinery, initiated by the chromatin-associated factor BAF1 and the nuclear-envelope-associated factor LEM2. Because telomeres are enriched at the reforming envelope, we investigated whether ESCRT factors contribute to telomere [...] Read more.
During open mitosis, reassembly of the nuclear envelope requires the coordinated recruitment of the ESCRT machinery, initiated by the chromatin-associated factor BAF1 and the nuclear-envelope-associated factor LEM2. Because telomeres are enriched at the reforming envelope, we investigated whether ESCRT factors contribute to telomere integrity. Reduction in the pivotal nuclear ESCRT factor CHMP7 caused DNA damage, heterochromatin disorganization, and telomere defects, including sister telomere associations and telomere free ends. Extending this analysis, we found that additional ESCRT components, including TSG101, VPS28, CHMP4B, and the ESCRT-associated factor AKTIP/Ft1, also contribute to telomere integrity, although with different strengths. Genetic interaction analyses suggest that CHMP7 converges in a common pathway with CHMP4B and AKTIP/Ft1, while it functions in parallel routes to TNKS1, a telomere-specific regulator of the shelterin TRF1. More genetic analyses indicated that BAF1 and LEM2 contribute to safeguarding of telomeres during nuclear envelope reassembly. Because defects in nuclear envelope dynamics and chromatin–membrane coupling are hallmarks of disorders associated with nuclear deformation and fragility, including aging and cancer, our findings contribute a new angle into these conditions and suggest potential targets for selectively modulating telomere maintenance pathways. Full article
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37 pages, 1347 KB  
Article
Empowering Green Transformation: The Strategic Nexus of Innovation, Regulation, and Sustainability in Chinese SMEs
by Hasnain Javed, Marcus V. Goncalves and Hoorulanne Ali
Adm. Sci. 2026, 16(2), 67; https://doi.org/10.3390/admsci16020067 (registering DOI) - 29 Jan 2026
Abstract
Growing pressure for sustainability has intensified the need for small- and medium-sized enterprises (SMEs) to adopt environmental innovation while maintaining competitive performance. This study examines how green innovation strategy, environmental regulations, and green absorptive capacity jointly shape the sustainable performance of Chinese manufacturing [...] Read more.
Growing pressure for sustainability has intensified the need for small- and medium-sized enterprises (SMEs) to adopt environmental innovation while maintaining competitive performance. This study examines how green innovation strategy, environmental regulations, and green absorptive capacity jointly shape the sustainable performance of Chinese manufacturing SMEs. Drawing on Resource-Based View, Institutional Theory, and Dynamic Capability Theory, we develop and empirically test a model that positions green innovation as a mediating mechanism linking strategic intent and regulatory forces to environmental, social, and economic performance outcomes. Data were collected through a structured survey of 250 SME managers in Jiangsu Province and analyzed using PLS-SEM. Results show that green innovation strategy significantly enhances both green innovation and sustainability performance, and that green innovation partially mediates the effects of both strategy and regulatory pressure on performance. While environmental regulations positively influence green innovation, they do not directly improve sustainability outcomes unless translated into innovation. Furthermore, green absorptive capacity displays a boundary-conditioning role, unexpectedly weakening the strategy–innovation path when knowledge integration exceeds implementation capacity. The findings extend the sustainability-oriented innovation literature by clarifying the indirect nature of regulation–performance linkages and revealing conditions under which absorptive capability accelerates or impedes green transformation. The study offers practical guidance for policymakers seeking to design innovation-enabling regulatory frameworks and for SMEs aiming to balance capability development with strategic focus to advance sustainability transitions. Full article
(This article belongs to the Special Issue Comprehensive Studies on the Development of International Business)
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14 pages, 823 KB  
Review
Genomic Subtypes and Computational Biomarkers in Non-Muscle-Invasive Bladder Cancer Guiding Optimal Timing of Radical Cystectomy and BCG Response Prediction
by Vlad-Horia Schițcu, Vlad Cristian Munteanu, Mihnea Bogdan Borz, Ion Cojocaru, Octavia Morari, Mircea Gîrbovan and Andrei-Ionuț Tișe
Genes 2026, 17(2), 153; https://doi.org/10.3390/genes17020153 (registering DOI) - 29 Jan 2026
Abstract
Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70% of newly diagnosed bladder cancer cases but exhibits significant clinical heterogeneity in treatment response and progression risk. While intravesical bacillus Calmette–GuérinCa (BCG) therapy remains the gold standard for high-risk disease, approximately 30–50% of patients experience [...] Read more.
Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70% of newly diagnosed bladder cancer cases but exhibits significant clinical heterogeneity in treatment response and progression risk. While intravesical bacillus Calmette–GuérinCa (BCG) therapy remains the gold standard for high-risk disease, approximately 30–50% of patients experience BCG failure, creating a critical decision point between additional bladder-sparing therapy (BST) and early radical cystectomy (RC). Recent clinical data from the CISTO study suggest that, in appropriately selected patients, RC may be associated with higher 12-month recurrence-free survival while maintaining comparable cancer-specific survival and physical functioning. In this narrative review, we synthesize contemporary evidence on NMIBC genomic and transcriptomic subtypes, immune contexture, and clinicopathologic features associated with BCG response and progression risk, with emphasis on clinically oriented classification systems such as BCG Response Subtypes (BRS1–3) and UROMOL21. We highlight how tumor-intrinsic biology (e.g., EMT-associated programs), immune phenotypes (inflamed vs. immune-cold microenvironments), and genomic alterations may help refine risk stratification beyond traditional clinicopathologic models. To facilitate clinical integration, we propose a conceptual decisional framework that combines molecular subtype assignment, immune profiling, key pathologic risk factors, and patient considerations to generate probabilistic risk tiers that support selection among early RC, BST, and clinical trial strategies. Standardized multicenter cohorts and prospective evaluation are needed to validate integrated models and define their clinical utility for the precision timing of cystectomy in BCG-unresponsive NMIBC. Full article
(This article belongs to the Special Issue Computational Genomics and Bioinformatics of Cancer)
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17 pages, 485 KB  
Article
Perceived Social Support and Well-Being: Mediation and Buffering of the Stress–Depression Link in Rural Older Adults
by Paul Alan Arkin Alvarado-García, Taniht Lisseth Cubas Romero, Lis Paola Reyes Sánchez, Valeria Alexxandra Sandoval Bocanegra and Marilú Roxana Soto-Vásquez
Healthcare 2026, 14(3), 336; https://doi.org/10.3390/healthcare14030336 (registering DOI) - 29 Jan 2026
Abstract
Background/Objectives: Rural older adults are exposed to multiple chronic stressors that may heighten depressive symptoms, and these effects can be intensified by social disconnection, particularly in resource-constrained settings. This study examined whether global and dimension-specific perceived social support—an indicator of perceived social connection—mediates [...] Read more.
Background/Objectives: Rural older adults are exposed to multiple chronic stressors that may heighten depressive symptoms, and these effects can be intensified by social disconnection, particularly in resource-constrained settings. This study examined whether global and dimension-specific perceived social support—an indicator of perceived social connection—mediates and/or buffers the association between perceived stress and depressive symptoms in rural older adults from northern Peru. Methods: A cross-sectional survey was conducted with 166 community-dwelling adults aged ≥60 years in a rural coastal district. Perceived stress (PSS-4), depressive symptoms (GDS-15), and perceived social support (MOS-SSS) were assessed. Regression-based mediation and moderation models with bootstrapped confidence intervals were estimated, adjusting for age, sex, marital status, education, income category, and chronic medical conditions. Results: Higher perceived stress was associated with greater depressive symptoms. Greater overall social support was associated with lower perceived stress and fewer depressive symptoms. Indirect effects supported a stress-process pathway for overall support, particularly socioemotional dimensions (positive social interaction and affectionate support). No buffering effect was observed for overall support; however, tangible (instrumental) support attenuated the association between stress and depressive symptoms. Conclusions: Mediation analyses supported an indirect pathway linking perceived stress to depressive symptoms via socioemotional support, whereas tangible (instrumental) support moderated the stress–depression association. Interventions that strengthen social connectedness and practical assistance may help protect mental health in rural older adults. Full article
(This article belongs to the Special Issue Impact of Social Connections on Well-Being of Older Adults)
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27 pages, 3158 KB  
Article
Data-Driven Planning for Casualty Evacuation and Treatment in Sustainable Humanitarian Logistics
by Shahla Jahangiri, Mohammad Bagher Fakhrzad, Hasan Hosseini Nasab, Hasan Khademi Zare and Majid Movahedi Rad
Algorithms 2026, 19(2), 104; https://doi.org/10.3390/a19020104 (registering DOI) - 29 Jan 2026
Abstract
After large-scale disasters, swift and robust humanitarian logistics are crucial to provide timely assistance to injured people and displaced individuals. This study proposes a bi-objective optimization model for humanitarian logistics network design to simultaneously consider the facility location-allocation decisions, along with the transportation [...] Read more.
After large-scale disasters, swift and robust humanitarian logistics are crucial to provide timely assistance to injured people and displaced individuals. This study proposes a bi-objective optimization model for humanitarian logistics network design to simultaneously consider the facility location-allocation decisions, along with the transportation operation issues under uncertainty. The framework addresses the needs of both severely and mildly injured casualties and homeless populations. A hybrid robust optimization approach is accordingly developed that incorporates scenario-based, box-type, and polyhedral uncertainty representations to handle the uncertainty of factors such as casualty volume, travel times, facility failures, and demands for resources. More recently, machine learning methods have been applied to classify casualties and displaced individuals with respect to their geographic distribution and severity, further improving demand estimates and operational efficacy. This study seeks to develop a data-driven and robust optimization framework for designing humanitarian logistics networks under uncertainty, enabling decision-makers and emergency planners to gain insights into enhancing casualty evacuation, medical treatment, and shelter allocation in disaster response operations. The case of the Kermanshah earthquake in Iran is used for assessing the applicability of the model. The computational experiments and comparative analyses conducted show that the developed model exhibits high efficiency and robustness. The results are useful for guiding disaster preparedness and strategic decisions in humanitarian logistics. Besides operational performance, the model optimizes sustainability in the area of emergency response based on cost efficiency and social fairness, as underlined by SDGs 3 and 11. Full article
(This article belongs to the Special Issue Computational Intelligence for Sustainable Operations and Circular Economy)
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14 pages, 1176 KB  
Article
The Role of Biodegradable Temporizing Matrix in Hand Surgery for Paediatric Recessive Dystrophic Epidermolysis Bullosa
by Aikaterini Bini, Michael Ndukwe, Greta Piccioli, Christina Lipede and Andrea Jester
J. Clin. Med. 2026, 15(3), 1059; https://doi.org/10.3390/jcm15031059 (registering DOI) - 29 Jan 2026
Abstract
Background/Objectives: The purpose of this study is to review the use of Biodegradable Temporizing Matrix (BTM) for releasing finger webspaces and flexion contractures in recessive dystrophic epidermolysis bullosa (RDEB) in paediatric patients and evaluate the short-term and mid-term results. Methods: Patients who underwent [...] Read more.
Background/Objectives: The purpose of this study is to review the use of Biodegradable Temporizing Matrix (BTM) for releasing finger webspaces and flexion contractures in recessive dystrophic epidermolysis bullosa (RDEB) in paediatric patients and evaluate the short-term and mid-term results. Methods: Patients who underwent release of webspace fusion and flexion contractures followed by BTM application during the last two years (2022–2024) were included. The data collected included the patient demographics, previous surgical management, type of release, post-operative complications and final outcomes. BTM was used in four patients. Results: The functional outcomes were acceptable but temporary, as three cases required or are planned for re-operation due to recurrence. Conclusion: The surgical experience using BTM as a single-stage dressing/dermal substitute in hand surgery for paediatric RDEB has shown feasibility and safety regarding infection rates. To the best of our knowledge, this is the first reported study regarding the BTM use for releasing hands in epidermolysis bullosa. Full article
(This article belongs to the Special Issue Plastic and Reconstructive Surgery: Cutting-Edge Expert Perspective)
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23 pages, 3230 KB  
Systematic Review
Pre-Eclampsia-Induced Maternal Liver Dysfunction: Systematic Review, Meta-Analysis and Meta-Regression of Observation Studies
by Kay-Lee E. Strauss, Wendy N. Phoswa and Kabelo Mokgalaboni
Life 2026, 16(2), 223; https://doi.org/10.3390/life16020223 (registering DOI) - 29 Jan 2026
Abstract
Introduction: Pre-eclampsia (PE) is a pregnancy-related hypertensive condition defined by the onset of hypertension after 20 weeks of gestation that is associated with proteinuria and maternal organ damage or uteroplacental dysfunction. It continues to be a leading cause of maternal and perinatal [...] Read more.
Introduction: Pre-eclampsia (PE) is a pregnancy-related hypertensive condition defined by the onset of hypertension after 20 weeks of gestation that is associated with proteinuria and maternal organ damage or uteroplacental dysfunction. It continues to be a leading cause of maternal and perinatal morbidity and mortality globally. PE is linked to systemic inflammation, endothelial dysfunction, and oxidative stress, which may compromise hepatic function. Aim: This meta-analysis assesses the impact of PE on maternal liver function by evaluating hepatic biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin. Methods: This meta-analysis of observational studies in Epidemiology (MOOSE) involved a search of PubMed and Scopus and manual screening of studies published between 2000 and 2025. Eligible studies included cross-sectional, case–control, and cohort designs. The quality of the studies was evaluated using the Newcastle–Ottawa Scale. Statistical analysis was conducted using the online meta-analysis, Jamovi version 2.6.44, and IBM SPSS Statistics version 30, and effect estimates were reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Forty-five studies, comprising 257,929 women 9420 with PE; 248,509 normotensive, were included. Women with PE had elevated AST, MD = 1.81 (95% CI: 1.51 to 2.10; p < 0.0001) and ALT, SMD = 1.73 (95% CI: 1.38 to 2.07; p < 0.0001); ALP, SMD = 1.43 (95% CI: 0.97 to 1.88; p < 0.0001); and total serum bilirubin (TSB), SMD = 0.62 (95% CI: 0.36 to 0.88; p < 0.0001) in comparison to normotensive controls. In the meta-regression, maternal age and quality were significant moderators, with older age and high-quality studies associated with smaller and larger effect sizes, respectively, for ALP (β = −0.720 and β = 1.444) and TSB (β = −0.304 and β = 0.761). For every 1-unit increase in body mass index, there was a significant 0.406-unit decrease in ALT effect size. Conclusions: PE is significantly associated with elevated maternal hepatic enzyme levels, indicating hepatocellular damage and impaired liver function. These findings emphasise the necessity for routine liver function monitoring in pregnant women with hypertensive disorders. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Preeclampsia)
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13 pages, 272 KB  
Article
Antimicrobial Susceptibility Patterns and Biofilm Formation of Staphylococcus aureus Strains Isolated from Pediatric Patients with Atopic Dermatitis
by Carolina Romo-González, Alejandra Aquino-Andrade, Abril Pérez-Carranza, Diana Chaparro-Camacho, Andrea Becerril-Osnaya and Maria Teresa García-Romero
Microorganisms 2026, 14(2), 311; https://doi.org/10.3390/microorganisms14020311 (registering DOI) - 29 Jan 2026
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier dysfunction and susceptibility to Staphylococcus aureus colonization. Biofilm formation modifies antibiotic resistance and the host immune response. This longitudinal study analyzed antimicrobial susceptibility and biofilm formation in 136 S. aureus isolates [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier dysfunction and susceptibility to Staphylococcus aureus colonization. Biofilm formation modifies antibiotic resistance and the host immune response. This longitudinal study analyzed antimicrobial susceptibility and biofilm formation in 136 S. aureus isolates obtained over 18 months from lesional, nonlesional, and nasal samples of 26 pediatric patients with moderate-to-severe AD. Antimicrobial susceptibility testing was determined by the disk diffusion method, and biofilm production was quantified using a crystal violet microtiter assay. Clinical parameters, including disease severity, treatment response, and the administration of dilute bleach baths, were evaluated in relation to bacterial characteristics. Overall, 60.2% of isolates exhibited moderate-to-strong biofilm production, significantly associated with severe AD at baseline (p = 0.01), lack of clinical improvement (p = 0.04), and persistent moderate-to-severe disease (p = 0.01). Resistance rates for penicillin, gentamicin, clindamycin, and erythromycin exceeded 15%. Isolates from patients using dilute bleach baths showed greater resistance to ciprofloxacin (p < 0.0001) and exhibited constitutive or inducible macrolide–lincosamide–streptogramin B (MLSB) resistance, with ermA detected in 80% of inducible cases. In conclusion, S. aureus biofilm formation is linked to disease severity and treatment failure in pediatric AD, underscoring the importance of culture-guided, targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Drug Resistance and Molecular Research of Staphylococcus spp.)
60 pages, 1664 KB  
Review
Vortices and Turbulence in Incompressible Fluids: An Introductory Review
by Koichi Takahashi
J 2026, 9(1), 4; https://doi.org/10.3390/j9010004 (registering DOI) - 28 Jan 2026
Abstract
Since Reynolds’ work, turbulence has been one of the most important subjects in fluid dynamics. Although its complete understanding seems still out of reach, there is at least one established physical basis that turbulence is a phenomenon of a random but non-trivially correlated [...] Read more.
Since Reynolds’ work, turbulence has been one of the most important subjects in fluid dynamics. Although its complete understanding seems still out of reach, there is at least one established physical basis that turbulence is a phenomenon of a random but non-trivially correlated assembly of vortices. The knowledge of vortices has thus become a prerequisite for promoting our understanding of the nature of turbulence. In this article, we first review the simple, compact vortex solutions to the Navier–Stokes equations for incompressible viscous fluids and a unified view of a certain type of vortices including Burgers, Sullivan and Bellamy-Knights solutions. The non-equivalence of the inviscid limit of the Navier–Stokes equations and the Euler equations is emphasized. Introducing the notion of observational non-uniqueness, which differs from the non-uniqueness in a certain class of differential equations, of solutions to the Navier–Stokes equations, the observation problem associated with the dense distribution of non-equivalent solutions is argued. The origin of the extreme sensitivity of the solutions to the boundary conditions is clarified. A few examples of vortex phenomena in the real world are also surveyed. We next review the works of constructing turbulence as a random assembly of simple, compact vortices. An attempt to combine the vortex model of turbulence with the Kármán–Howarth equation for the velocity correlation functions of anisotropic turbulence is presented. It is pointed out that the studies in this direction suggested that Kolmogorov’s 2/3 scaling law was generally compatible with anisotropy. A few quantities are proposed as candidates to measure anisotropy in turbulence experiments. Full article
(This article belongs to the Section Physical Sciences)
10 pages, 493 KB  
Article
Quantifying UV-Driven Aging of Sub-10 µm Airborne Microplastics with High-Resolution µFTIR-ATR Imaging
by Yasuhiro Niida, Yusuke Fujii, Yukari Inatsugi and Norimichi Takenaka
Atmosphere 2026, 17(2), 146; https://doi.org/10.3390/atmos17020146 (registering DOI) - 28 Jan 2026
Abstract
Airborne microplastics (AMPs) undergo ultraviolet (UV)-driven physicochemical aging during atmospheric transport, influencing cloud processes, greenhouse-gas release, and potential respiratory health impacts. Quantifying this transformation is particularly challenging for particles smaller than 10 µm and for polymers such as polyethylene terephthalate (PET), whose intrinsic [...] Read more.
Airborne microplastics (AMPs) undergo ultraviolet (UV)-driven physicochemical aging during atmospheric transport, influencing cloud processes, greenhouse-gas release, and potential respiratory health impacts. Quantifying this transformation is particularly challenging for particles smaller than 10 µm and for polymers such as polyethylene terephthalate (PET), whose intrinsic ester carbonyl band obscures newly formed acid carbonyls in conventional infrared analyses. Here, we develop a µFTIR attenuated total reflection (µFTIR-ATR) imaging method combined with a fourth-derivative oxidation index (carbonyl ratio at 1701/1716 cm−1) that resolves these overlapping bands and enables sensitive, quantitative evaluation of PET surface oxidation. The approach automates detection, identification, and oxidation analysis of particles down to ~2 µm. Laboratory UV irradiation experiments show a systematic increase in this derivative-based oxidation index with exposure dose. Application to ambient PET collected from Mt. Fuji, Tokyo, Osaka (Japan), and Siem Reap (Cambodia) reveals clear regional differences corresponding to local UV-A environments: PET from Siem Reap exhibited the highest oxidation, whereas particles from the Japanese sites showed moderate but variable aging. These results demonstrate that derivative-based µFTIR-ATR imaging provides a practical and highly sensitive tool for quantifying photo-oxidative degradation in fine AMPs and highlight the value of chemical-aging metrics for interpreting atmospheric processing and transport pathways. Full article
(This article belongs to the Special Issue Micro- and Nanoplastics in the Atmosphere)
16 pages, 2074 KB  
Article
A Proteomic Study of the Dual Oncogenic and Tumor-Suppressive Roles of SIRT3 in Lung and Breast Cancer Cell Lines
by Marisol Ayala Reyes, Diana Lashidua Fernández Coto, Ramiro Alonso Bastida, György Marko-Varga, Jeovanis Gil and Sergio Encarnacion Guevara
Int. J. Mol. Sci. 2026, 27(3), 1325; https://doi.org/10.3390/ijms27031325 (registering DOI) - 28 Jan 2026
Abstract
Mitochondria play a crucial role in metabolism and energy production by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They also help maintain intracellular calcium levels, facilitate communication between the nucleus and cytoplasm, detoxify reactive oxygen species (ROS), and regulate apoptosis. Reversible acetylation of [...] Read more.
Mitochondria play a crucial role in metabolism and energy production by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They also help maintain intracellular calcium levels, facilitate communication between the nucleus and cytoplasm, detoxify reactive oxygen species (ROS), and regulate apoptosis. Reversible acetylation of mitochondrial proteins is a key post-translational modification influencing these processes, with the NAD+-dependent deacetylase SIRT3 being a major regulator. While SIRT3 has been described as a tumor suppressor in some contexts and as a tumor promoter in others, its role appears to be tissue- and metabolism-specific. Here, we compared the proteomic and acetylomic responses of lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7) cell lines to SIRT3 inhibition by 3-TYP. The two lines were selected based on distinct metabolic phenotypes and reported differences in basal SIRT3 abundance. Total proteome and mitochondrial-enriched fractions were analyzed separately for each cell line to avoid cross-line normalization bias. We identified 6457 proteins and 4199 acetylated peptides, revealing distinct pathway enrichments and acetylation changes after SIRT3 inhibition. A549 cells showed increased oxidative metabolism, while MCF7 cells exhibited metabolic reprogramming. These results indicate that the proteomic impact of SIRT3 modulation is strongly influenced by cellular metabolic context. All raw mass spectrometry data are publicly available in PXD063181. Full article
(This article belongs to the Collection Advances in Cell and Molecular Biology)
24 pages, 2346 KB  
Article
Design and Biological Evaluation of Mannich-Modified 8-Hydroxyquinoline–Phthalimide Hybrids Against Drug-Resistant Cancer Cells
by Moamen A. Hassanin, Márta Nové, Gabriella Spengler, István Szatmári and Péter Simon
Pharmaceuticals 2026, 19(2), 230; https://doi.org/10.3390/ph19020230 (registering DOI) - 28 Jan 2026
Abstract
Background: 8-Hydroxyquinoline and phthalimide are two significant heterocyclic scaffolds in medicinal chemistry due to their pharmacological profiles. Hybridizing these pharmacophores and further modifying them via modified Mannich reactions provides a strategy to improve their physicochemical parameters and selectivity toward multidrug-resistant (MDR) cancer cells. [...] Read more.
Background: 8-Hydroxyquinoline and phthalimide are two significant heterocyclic scaffolds in medicinal chemistry due to their pharmacological profiles. Hybridizing these pharmacophores and further modifying them via modified Mannich reactions provides a strategy to improve their physicochemical parameters and selectivity toward multidrug-resistant (MDR) cancer cells. Objectives: To synthesize a series of 8-hydroxyquinoline–phthalimide hybrids and their Mannich base derivatives and evaluate their cytotoxic activity and resistance-selective properties against sensitive Colo205 and resistant Colo320 cancer cell lines. Methods: Four hybrid compounds were synthesized by reacting 5-amino-8-hydroxyquinoline with different phthalic anhydride derivatives. Twelve fine-tuned derivatives were prepared by using the modified Mannich reaction. Cytotoxic activity was measured using the MTT assay, and relative resistance (RR) was calculated to determine selectivity toward the resistant cell line. P-glycoprotein (Pgp) ATPase activity was evaluated for the most active compounds. Results: All derivatives displayed cytotoxic activity, with higher potency toward the resistant Colo320 cell line. Compounds 2 and 4 showed the strongest activity against both cell lines (IC50 down to 4.88 µM). Compounds 5, 8a, 9a, and 9c retained potent activity against Colo320 (IC50 = 9.89–22.79 µM). Incorporating a CH2–N group at position C7 substantially enhanced the selectivity for MDR cells. Compounds 9c, 9a, and 8a exhibited the highest selectivity, with RR values of 0.29, 0.33, and 0.35, respectively. Compounds 2, 4, 5, 8a, and 9a showed inhibitory effects on Pgp ATPase activity. Conclusion: The newly synthesized HQ–phthalimide hybrids represent promising candidates for targeting MDR in colorectal cancer, with Mannich modification enhancing the selectivity toward resistant cells. Full article
(This article belongs to the Special Issue Novel Heterocyclic Compounds as Potential Anti-Inflammatory and/or Anticancer Agents)
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31 pages, 8851 KB  
Article
Design, Manufacturing and Experimental Validation of an Integrated Wing Ice Protection System in a Hybrid Laminar Flow Control Leading Edge Demonstrator
by Ionut Brinza, Teodor Lucian Grigorie and Grigore Cican
Appl. Sci. 2026, 16(3), 1347; https://doi.org/10.3390/app16031347 (registering DOI) - 28 Jan 2026
Abstract
This paper presents the design, manufacturing, instrumentation and validation by tests (ground and icing wind tunnel) of a full-scale Hybrid Laminar Flow Control (HLFC) leading-edge demonstrator based on Airbus A330 outer wing plan-form. The Ground-Based Demonstrator (GBD) was developed to reproduce a full-scale, [...] Read more.
This paper presents the design, manufacturing, instrumentation and validation by tests (ground and icing wind tunnel) of a full-scale Hybrid Laminar Flow Control (HLFC) leading-edge demonstrator based on Airbus A330 outer wing plan-form. The Ground-Based Demonstrator (GBD) was developed to reproduce a full-scale, realistic wing section integrating into the leading-edge three key systems: micro-perforated skin for the hybrid laminar flow control suction system (HLFC), the hot-air Wing Ice Protection System (WIPS) and a folding “bull nose” Krueger high-lift device. The demonstrator combines a superplastic-formed and diffusion-bonded (SPF/DB) perforated titanium skin mounted on aluminum ribs jointed with a carbon-fiber-reinforced polymer (CFRP) wing box. Titanium internal ducts were designed to ensure uniform hot-air distribution and structural compatibility with composite components. Manufacturing employed advanced aeronautical processes and precision assembly under INCAS coordination. Ground tests were performed using a dedicated hot-air and vacuum rig delivering up to 200 °C and 1.6 bar, thermocouples and pressure sensors. The results confirmed uniform heating (±2 °C deviation) and stable operation of the WIPS without structural distortion. Relevant tests were performed in the CIRA Icing Wind Tunnel facility, verifying the anti-ice protection system and Krueger device. The successful design, fabrication, testing and validation of this multifunctional leading edge—featuring integrated HLFC, WIPS and Krueger systems—demonstrates the readiness of the concept for subsequent aerodynamic testing. Full article
(This article belongs to the Special Issue 5th Anniversary of Aerospace Science and Engineering Section—Recent Advances in Aerospace)
23 pages, 5087 KB  
Article
Targeting SARS-CoV-2 Main Protease: A Bacteria-Based Colorimetric Assay for Screening Natural Antiviral Inhibitors
by Shaza S. Issa, Andrew A. Zelinsky, Haidar J. Fayoud, Roman R. Zhidkin and Tatiana V. Matveeva
Viruses 2026, 18(2), 178; https://doi.org/10.3390/v18020178 (registering DOI) - 28 Jan 2026
Abstract
SARS-CoV-2 main protease (Mpro) is essential for viral polyprotein processing and represents a prime target for antiviral drug discovery. However, most available screening strategies rely on computational predictions or cell-free biochemical approaches that provide limited functional context and often require specialized [...] Read more.
SARS-CoV-2 main protease (Mpro) is essential for viral polyprotein processing and represents a prime target for antiviral drug discovery. However, most available screening strategies rely on computational predictions or cell-free biochemical approaches that provide limited functional context and often require specialized instrumentation, while mammalian cell-based models remain costly and require high biosafety levels. Accordingly, there remains a shortage of simple, rapid, and biosafe functional screening tools suitable for early-stage prioritization of potential Mpro inhibitors, particularly those derived from natural sources and in urgent situations such as the COVID-19 pandemic. In this study, a bacterial colorimetric reporter assay was developed that directly links SARS-CoV-2 Mpro activity to β-galactosidase function in Escherichia coli. To the best of our knowledge, the developed assay represents the first bacterial colorimetric model for functional detection of SARS-CoV-2 Mpro inhibition based on a phenotypic readout. The assay enables the rapid visual detection of protease inhibition on X-gal-containing medium and provides a cost-effective and biosafe platform for prioritizing candidate inhibitors, under standard laboratory conditions, prior to further validation. Due to its bacterial expression context, this assay is intended for functional screening to provide the most promising candidate compounds and/or extracts for subsequent biochemical or mammalian cell-based validation; it is not intended to determine quantitative potency or to replace further validation approaches. It should be noted that the selective compound uptake in E. coli restricts the range of chemical compositions that can be evaluated using this method. Therefore, proof-of-concept application was demonstrated using pomegranate juice, a representative natural inhibitor source, rather than most currently known specific Mpro inhibitors. In addition, other plant-derived preparations, including rhubarb, grape, and red/black currant juices, were tested demonstrating the assay’s applicability to diverse natural matrices. Full article
(This article belongs to the Special Issue Natural, Semisynthetic, and Synthetic Antiviral Drugs Targeting HIV and SARS-CoV-2)
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24 pages, 6752 KB  
Article
Genomic Epidemiology of Carbapenem-Resistant Acinetobacter baumannii Isolated from Patients Admitted to Intensive Care Units in Network Hospitals in Southern Thailand
by Arnon Chukamnerd, Komwit Surachat, Rattanaruji Pomwised, Prasit Palittapongarnpim, Kamonnut Singkhamanan and Sarunyou Chusri
Antibiotics 2026, 15(2), 133; https://doi.org/10.3390/antibiotics15020133 - 28 Jan 2026
Abstract
Background/Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) is classified as an urgent-threat pathogen because of its resistance to nearly all available antibiotics, resulting in high morbidity and mortality rates. However, data on the molecular epidemiology of CRAB isolates in southern Thailand are limited. This [...] Read more.
Background/Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) is classified as an urgent-threat pathogen because of its resistance to nearly all available antibiotics, resulting in high morbidity and mortality rates. However, data on the molecular epidemiology of CRAB isolates in southern Thailand are limited. This study aimed to investigate the genomic epidemiology of CRAB isolates within a hospital network in lower southern Thailand. Methods: Whole-genome sequencing data of CRAB clinical isolates (n = 224) were obtained from a previous study. Additional isolates (n = 70) were included, for which genomic DNA was extracted and sequenced. In total, 294 isolates were collected from patients across seven hospitals in southern Thailand between 2019 and 2020. Their genomes were analyzed using several bioinformatic tools. Results: A high proportion of isolates were obtained from sputum samples of patients with CRAB infection or colonization. Sequence type (ST) 2 was the most frequent ST and was classified in the quadrant with high resistance and virulence. The Sankey diagram showed that ST2 was the dominant and most versatile CRAB lineage circulating across major hospitals, commonly associated with pneumonia, and that diverse resistance genes and plasmid combinations were dominated by blaOXA-23. The core single-nucleotide polymorphism (SNP)-based phylogenetic tree revealed clades A1 (ST215), A2 (multiple STs), and B (ST2). Bloodstream, skin, and soft tissue infections were predominantly observed in clade B. Conclusions: Our analysis revealed widespread circulation of a high-risk ST2 CRAB lineage with enhanced resistance and virulence across hospital networks in the studied region, highlighting the importance of genomics-informed surveillance for controlling CRAB dissemination. Full article
(This article belongs to the Special Issue Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Clinical Gram-Negative Bacteria)
36 pages, 22348 KB  
Article
Fire Evacuation Performance Simulation of Staircases Under Two Renovation Strategies for Early Modern Brick–Timber Buildings: A Case Study of a Hui-Shaped Chinese Baroque Architecture in Harbin
by Yongze Li, Jianmei Wu, Lei Zhang, Jiajia Teng, Xiaodan Liu, Conrong Wang, Kai Kan and Jianlin Mao
Buildings 2026, 16(3), 548; https://doi.org/10.3390/buildings16030548 - 28 Jan 2026
Abstract
It is a common phenomenon that the stairs of modern historical brick–timber buildings cannot meet existing fire protection specifications, something which has become a difficulty in their renovation. In response, this study proposes two different renovation strategies for the Hui-shaped Chinese Baroque brick–timber [...] Read more.
It is a common phenomenon that the stairs of modern historical brick–timber buildings cannot meet existing fire protection specifications, something which has become a difficulty in their renovation. In response, this study proposes two different renovation strategies for the Hui-shaped Chinese Baroque brick–timber building in Harbin and constructs multiple fire scenarios. Using a coupled PyroSim–Pathfinder (version 2023.2.0816) simulation approach, a finite element model of the building under fire and a corresponding evacuation model are established. The aim is to investigate how variations in stair width, number, position, and overall building scale under the two renovation strategies influence evacuation movement time and the number of evacuation failures, and to compare the effectiveness of common fire protection measures. The results show that, for the same stair configuration and building mass, the fire development patterns of the two renovation strategies are similar. Increasing the stair width from the original 0.9 m to 1.1 m produces no significant improvement in evacuation performance. When the number of indoor existing stairways increases from one to two, the proportion of occupants evacuated safely rises from 68% to 91%. External corridor staircases provide the best evacuation performance, and a single such stair can satisfy the safe evacuation of all occupants. When the same additional floor area is provided, increasing the number of storeys extends the evacuation movement time by approximately twice that caused by increasing the building footprint. Automatic sprinkler systems and mechanical smoke exhaust systems exhibit more pronounced fire protection effects. Full article
(This article belongs to the Section Architectural Design, Urban Science, and Real Estate)
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19 pages, 1719 KB  
Article
Critical Hypercytokinemia in Sepsis and Septic Shock: Identifying Interleukin-6 Thresholds Beyond Which Mortality Risk Exceeded Survival Probability
by Juan Carlos Ruiz-Rodríguez, Luis Chiscano-Camón, Adolf Ruiz-Sanmartin, Natalia Costa-Allué, Ivan Bajaña, Pablo Nicolas-Morales, Juliana Bastidas, Sergi Cantenys-Molina, Manuel Hernández-Gonzalez, Nieves Larrosa, Juan Jose González-López, Vicent Ribas and Ricard Ferrer
J. Clin. Med. 2026, 15(3), 1057; https://doi.org/10.3390/jcm15031057 - 28 Jan 2026
Abstract
Introduction: Patients with extremely elevated IL-6 levels remain poorly characterized, and no specific plasma concentration has been established to reliably predict mortality or guide immunomodulatory interventions. We hypothesized that extreme hypercytokinemia is associated with increased mortality in sepsis. The primary objective was [...] Read more.
Introduction: Patients with extremely elevated IL-6 levels remain poorly characterized, and no specific plasma concentration has been established to reliably predict mortality or guide immunomodulatory interventions. We hypothesized that extreme hypercytokinemia is associated with increased mortality in sepsis. The primary objective was to identify, in patients with hyperinflammatory endotype, an IL-6 threshold associated with a significantly elevated risk of death. Methods: We conducted a retrospective, single-center observational study based on a historical cohort of adult patients with consecutive activation of the in-hospital sepsis code, a prospective and standardized institutional care pathway, at Vall d’Hebron University Hospital between July 2018 and December 2024. Patients fulfilling Sepsis-2 diagnostic criteria and criteria for severe sepsis or septic shock were eligible. Plasma interleukin-6 (IL-6) levels were routinely determined in all patients. The analysis included patients with complete clinical and laboratory data available in the study database. To identify the IL-6 threshold associated with critical risk of death, a cumulative conditional relative frequency analysis was performed. A quantile-based analysis was conducted using predefined intervals of 1000 pg/mL and 15,000 pg/mL. A multivariable logistic regression analysis was conducted to identify clinical and laboratory parameters independently associated with IL-6 > 15,000 pg/mL and outcome. Results are presented as odds ratios (ORs). Survival differences were assessed using Kaplan–Meier analysis. Results: Overall mortality was 31% in the 1669 patients analyzed. Median IL-6 concentration was 772 pg/mL (IQR: 164–8750 pg/mL) with significantly higher levels in non-survivors (2137 pg/mL, IQR: 267–34,758). A critical IL-6 cutoff of 14,930 pg/mL was identified, which was rounded to 15,000 pg/mL for clinical applicability. IL-6 > 15,000 pg/mL was associated with increased mortality (OR 2.22, 95% CI: 1.12–5.36). Kaplan–Meier analysis revealed significantly reduced survival in patients above this IL-6 threshold (p < 0.0001). Conclusions: In this cohort of patients with severe sepsis or septic shock, plasma IL-6 levels > 15,000 pg/mL defined a critical threshold beyond which mortality risk exceeded survival probability. Critical hypercytokinemia may serve as a clinically relevant biomarker to identify patients with sepsis and multiorgan dysfunction who could benefit from precision immunomodulatory therapies. Full article
(This article belongs to the Section Intensive Care)
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45 pages, 3692 KB  
Review
Interactions Between Nutraceuticals and α-Synuclein Conformational States: Molecular Mechanisms and Neuroprotective Implications in Parkinson’s Disease
by Bruna Amenta, Rosalba Minervini, Maria Laura Matrella and Tiziana Cocco
Int. J. Mol. Sci. 2026, 27(3), 1324; https://doi.org/10.3390/ijms27031324 - 28 Jan 2026
Abstract
Synucleinopathies, including Parkinson’s disease (PD), are neurodegenerative disorders characterized by aberrant aggregation of α-synuclein (α-syn), a presynaptic protein with an intrinsic disorder nature. The transition of soluble monomers into oligomeric and fibrillar species represents a key molecular event driving neuronal dysfunction and neurodegeneration. [...] Read more.
Synucleinopathies, including Parkinson’s disease (PD), are neurodegenerative disorders characterized by aberrant aggregation of α-synuclein (α-syn), a presynaptic protein with an intrinsic disorder nature. The transition of soluble monomers into oligomeric and fibrillar species represents a key molecular event driving neuronal dysfunction and neurodegeneration. Emerging evidence suggests that nutraceuticals, bioactive compounds derived from dietary sources, can modulate α-syn aggregation at multiple conformational stages. Polyphenols, alkaloids, ginsenosides, and food-derived peptides interfere with α-syn structure and assembly, suppressing the formation of toxic oligomer species and promoting the clearance of misfolded assemblies. Despite this potential, clinical translational of nutraceuticals is currently limited by poor systemic bioavailability and restricted central nervous system penetration due to blood–brain barrier constraints, which have largely confined research to preclinical studies. In this context, this review summarizes current knowledge of nutraceutical interventions targeting the conformational landscape of α-syn and highlighting both direct and indirect molecular mechanisms with involved in aggregation-prone species. Furthermore, we critically examine key challenges related to bioavailability and clinical translation, focusing on advanced delivery systems and precision-based approaches to enhance neuroprotective efficacy and support the potential of nutraceuticals as novel or adjunctive therapeutic strategies for PD. Full article
(This article belongs to the Special Issue The Role of Natural Products in Drug Discovery: 2nd Edition)
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26 pages, 2852 KB  
Review
Targeting Pathways Implicated in Cholesterol Metabolism for Novel Cancer Therapy
by Yi Zhou, Vishakha Sharma, Xiaoyu Li, Rajeev K. Singla, Ankush Kumar, Ashishkumar Kyada, Suhas Ballal, Deepak Nathiya, Apurva Koul, Mohammad Khalid, Monica Gulati, Sandeep Arora, Tapan Behl, Joachim Kavalakatt, Bairong Shen and Anupam Bishayee
Cancers 2026, 18(3), 428; https://doi.org/10.3390/cancers18030428 - 28 Jan 2026
Abstract
Cholesterol acts as a metabolic cue that reshapes diverse signaling networks, including hedgehog and several sterol-regulated pathways orchestrated by key proteins, including sterol regulatory element-binding protein 2 (SREBP2), sterol O-acyltransferase 1 (SOAT1), Niemann–Pick type C1 (NPC1), and proprotein convertase subtilisin/kexin type 9 (PCSK9). [...] Read more.
Cholesterol acts as a metabolic cue that reshapes diverse signaling networks, including hedgehog and several sterol-regulated pathways orchestrated by key proteins, including sterol regulatory element-binding protein 2 (SREBP2), sterol O-acyltransferase 1 (SOAT1), Niemann–Pick type C1 (NPC1), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Research over the past decade has highlighted cholesterol metabolism as a key modulator of cancer development and a promising therapeutic target. By integrating mechanistic and translational evidence, this review seeks to clarify how cholesterol metabolism interfaces with oncogenic signaling and set directions for future investigation. Accumulating preclinical and clinical data suggest that dysregulated cholesterol levels, often associated with high-fat diets, may contribute to tumorigenesis and malignant transformation. Implicated pathways, such as SREBP, NPC1, PCSK9, and SOAT1, orchestrate various processes of lipid metabolism, including cholesterol synthesis, esterification, receptor degradation, and transport, that harbor a tumorigenic environment and promote oncogenic processes. Additionally, these enzymes and corresponding pathways provide a promising direction for developing metabolism-oriented anticancer strategies. Cholesterol metabolism dysregulation serves as a major avenue for cancer signaling and growth, but studies also highlight key molecular mechanisms and targets for future treatments. Future studies should focus on expanding studies into further cancer types, investigating combination therapies, and developing novel inhibitors of key molecular targets. Full article
(This article belongs to the Special Issue Discovery and Development of New Anticancer Drugs and Delivery Systems: Special Emphasis on Artificial Intelligence, Machine-Learning, and Big Data Analysis)
20 pages, 463 KB  
Article
Insulation Monitoring and Fault Diagnosis Technology of Cross-Bonded Metal-Sheathed Cable
by Chunming Wei, Dewen Zhang, Chao Xu, Long Tan, Zhongzhi Qu and Bo Zhu
Energies 2026, 19(3), 698; https://doi.org/10.3390/en19030698 - 28 Jan 2026
Abstract
For addressing the challenge that cross-interconnection of metal sheaths in long-distance high-voltage cables complicates the monitoring of cable insulation faults, it is proposed a fault diagnosis scheme based on resistive current, dielectric loss factor, and sheath current. The voltage and current signals at [...] Read more.
For addressing the challenge that cross-interconnection of metal sheaths in long-distance high-voltage cables complicates the monitoring of cable insulation faults, it is proposed a fault diagnosis scheme based on resistive current, dielectric loss factor, and sheath current. The voltage and current signals at both ends of the cable are collected, as well as the current signals at the outlet of the grounding box and the transposition box. By establishing an equivalent model of the cross-connected cable, the calculation method for fault diagnosis is derived, and an implementation scheme for fault diagnosis is provided. The insulation monitoring method proposed in this paper is simulated and verified using MATLAB/Simulink software, with simulations conducted to investigate four typical faults: cable insulation fault, sheath open-circuit fault, transposition box immersion short-circuit fault, and cable intermediate-joint breakdown fault. The circuit model of the cross-connected unit is established in the laboratory to verify the method proposed in this paper. The results show that the simulation results are consistent with the test results, and the fault types can be correctly reflected, which verifies the correctness and effectiveness of the insulation monitoring method. Full article
(This article belongs to the Section F1: Electrical Power System)
17 pages, 1922 KB  
Article
Foundations of an Ovine Model of Fragile X Syndrome
by Victoria Hawkins, Skye R. Rudiger, Clive J. McLaughlan, Jennifer M. Kelly, Klaus Lehnert, Jessie C. Jacobsen, Renee R. Handley, Kimiora Henare, Paul J. Verma and Russell G. Snell
Genes 2026, 17(2), 152; https://doi.org/10.3390/genes17020152 - 28 Jan 2026
Abstract
Background: Fragile X Syndrome (FXS) is an X-linked neurodevelopmental disorder characterised by intellectual disability, developmental delays, anxiety, and social and behavioural challenges. Currently, no effective treatments exist to address the root cause of FXS. Mouse models are the most widely used for studying [...] Read more.
Background: Fragile X Syndrome (FXS) is an X-linked neurodevelopmental disorder characterised by intellectual disability, developmental delays, anxiety, and social and behavioural challenges. Currently, no effective treatments exist to address the root cause of FXS. Mouse models are the most widely used for studying molecular pathogenesis and conducting preclinical treatment testing. However, therapeutic interventions that show promise in rodent models have yet to succeed in clinical trials. After evaluating the current models, we have developed an ovine model to address this clinical translation gap. We expect this model to more accurately reflect the human condition in brain size, structure, and neurodevelopmental trajectory. We aim to establish this model as a valuable preclinical platform for testing therapies for FXS. Methods: To generate the sheep model, we used CRISPR-Cas9 dual-guide editing to knock out the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene in ovine embryos. Results: Two founder animals were created, one ram (male) and one ewe (female), both of which carried FMR1 gene knockouts. The ewe carries inactivating mutations on both alleles, with the edits in both animals resulting in no detectable Fragile X Messenger Ribonucleoprotein (FMRP) as expected. Both founders have undergone molecular characterisation and basic health checks, with the female founder showing increased joint flexibility, a characteristic of FXS. The ram has been used for breeding, with the successful transmission of the edited allele to his offspring. Importantly, specific lamb cohorts for postnatal treatment testing can be produced efficiently utilising accelerated breeding methods and preimplantation selection. Full article
(This article belongs to the Special Issue Fragile X Syndrome and Fragile X Premutation Associated Conditions)
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10 pages, 3517 KB  
Article
High-Extinction-Ratio Chiral Mid-Wave Infrared Photodetector Using Trapezoidal Si Pillars
by Yingsong Zheng, Longfeng Lv, Yuxiao Zou, Bo Cheng, Hanxiao Shao, Guofeng Song and Kunpeng Zhai
Micromachines 2026, 17(2), 181; https://doi.org/10.3390/mi17020181 - 28 Jan 2026
Abstract
Although the polarization state, as a key physical dimension of light, plays an irreplaceable role in many frontier fields such as quantum communication and chiral sensing, traditional photodetectors are limited by the inherent optical isotropy of materials and thus are unable to directly [...] Read more.
Although the polarization state, as a key physical dimension of light, plays an irreplaceable role in many frontier fields such as quantum communication and chiral sensing, traditional photodetectors are limited by the inherent optical isotropy of materials and thus are unable to directly distinguish circular polarization information. This paper numerically reports a miniature circular polarization photodetector based on chiral metasurfaces, which achieves an excellent extinction ratio of up to 31 dB through the collaborative regulation of geometric displacement manipulation and tilt angle operation. This device utilizes the symmetry-breaking effect to construct significantly different transmission spectral responses between left circularly polarized light (LCP) and right circularly polarized light (RCP). Our research not only provides a high-performance implementation solution for on-chip polarization detection but also opens up new paths for the future development of quantum optics, integrated sensing, and ultra-compact polarization optical systems. Full article
(This article belongs to the Special Issue Photonic and Optoelectronic Devices and Systems, 4th Edition)
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