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Background/Objectives: Discrepancies between measured indoor temperature and perceived comfort in hospital settings raise concerns about the role of visual environment in shaping sensory perception and psychological well-being. This study examined the effects of wall finish, wall color, and color temperature on thermal perception, visual perception, affect, perceived restoration, and EEG responses in patient rooms using virtual reality. Methods: In total, 192 participants were assigned to either a 20 °C or 25 °C ambient-temperature condition and exposed to one of 12 virtual patient-room scenes in a between-subjects experiment. Pre- and post-experimental survey data and EEG data were analyzed. Results: Compared with those tested at 20 °C, participants tested at 25 °C underestimated room temperature more and rated wall finish, wall color, and color temperature as more visually comfortable. At 20 °C, participants exposed to the latex paint finish condition rated the wall finish as visually more comfortable and reported greater willingness to rest than those in the vinyl wallcovering condition; however, EEG regression showed higher occipital alpha/beta ratio index values for vinyl wallcovering, indicating a relaxation-related EEG response. Under both temperature conditions, yellow walls led to warmer temperature estimation than blue or white walls. At 20 °C, warm color temperature produced warmer thermal sensation, more visually comfortable color-temperature ratings, higher room pleasantness, and greater willingness to rest than cool color temperature. Conclusions: Differences in perceptual, psychological, and EEG responses to patient-room visual environment should be interpreted together with ambient-temperature conditions in healthcare settings. Full article

(This article belongs to the Section Building Energy, Physics, Environment, and Systems)

20 pages, 288 KB

Open AccessArticle

Community Digital Nets: Mutual Support as Key to Tech Appropriation

by David Alonso-González, Juan Brea-Iglesias, Adrián Jesús Ricoy-Cano, Inmaculada Herranz-Aguayo, Raquel Ávila-Muñoz and Andrés Arias-Astray

Soc. Sci. 2026, 15(7), 450; https://doi.org/10.3390/socsci15070450 - 6 Jul 2026

Abstract

This study examines the processes of technology adoption and appropriation among older adults participating in two community-based digital inclusion workshops (LAB65+) in Madrid, exploring how digital technologies are appropriated within community learning environments and identifying the social, relational, and pedagogical factors that shape this process, with particular attention to the role of mutual support, warm experts, and community learning dynamics. Drawing on a series of workshops and group interaction recordings conducted with regular attendees, the research identifies a set of factors that consistently shape participants’ engagement with digital tools. Particular attention is given to socio-educational background, previous work experience, and prior exposure to technology, as well as to the everyday motivations associated with the use of mobile phones for communication through WhatsApp, online purchasing, access to health services, and routine banking procedures. Across both labs, the findings reveal that successful and sustained engagement with technology among older adults depends less on technical training per se than on elements related to motivation, self-efficacy, meaningful instruction, and the creation or reinforcement of social ties in familiar environments. Although minor differences emerge between the two settings, the evidence consistently underscores the centrality of these relational and contextual factors over purely operational or skill-based considerations. The study highlights the need for community-oriented approaches that recognize and build upon the social dimensions of learning and using technology in later life. Full article

(This article belongs to the Special Issue Contemporary Community Social Services: Issues and Challenges)

29 pages, 1049 KB

Open AccessReview

Natural Vitamin A-Related Compounds in Cosmetic Applications: From Retinoids to Carotenoids—Mechanisms, Efficacy and Regulatory Perspectives

by Karolina Łagosz and Agnieszka Gunia-Krzyżak

Appl. Sci. 2026, 16(13), 6789; https://doi.org/10.3390/app16136789 - 6 Jul 2026

Abstract

Natural bioactive compounds play an increasingly important role in modern cosmetic formulations, particularly in the context of efficacy, safety, and regulatory compliance. Among them, vitamin A-related compounds have attracted significant attention due to their well-documented effects on skin renewal, collagen synthesis, and photoaging prevention. This review provides a comprehensive overview of natural vitamin A derivatives and structurally related carotenoids used in cosmetic applications, including retinol, retinal, retinyl esters, β-carotene, lycopene, zeaxanthin, astaxanthin, lutein, and fucoxanthin. The article critically examines their intracellular mechanisms of action, distinguishing between canonical retinoid signaling pathways mediated by nuclear receptors (RAR/RXR) and the predominantly antioxidant activities of carotenoids. Particular attention is given to the metabolic conversion of provitamin A compounds and their relevance to biological activity in the skin. Furthermore, recent regulatory restrictions on the use of retinol and retinyl esters, especially within the European Union, are discussed in the context of formulation challenges and the growing interest in naturally derived alternatives. By integrating mechanistic insights with regulatory and application-oriented perspectives, this review highlights the potential and limitations of natural vitamin A-related compounds and outlines future directions for their use in safe and effective cosmetic products. Full article

20 pages, 4813 KB

Open AccessArticle

Differences of PPARD Expression in the Liver of Cattle with Different Marbling Grades

by Kaiyou Wang, Qi Wang, Qinyu Wang, Shuaiying Tian, Ying Qi, Lin Zhang, Baokui Xing, Tuliguer and Qiuling Li

Animals 2026, 16(13), 2096; https://doi.org/10.3390/ani16132096 - 6 Jul 2026

Abstract

Fat deposition determines beef marbling grade and meat quality, but the underlying molecular mechanisms remain unclear. This study aimed to investigate the role of bovine PPARD in lipid deposition, especially its effect on the expression of fatty acid transport genes (CD36, FATP1, and FABP1) and the lipid droplet-associated gene (PLIN2) in liver tissues from cattle with different marbling grades. The mRNA abundance and protein levels in liver tissues from thirty-one Wagyu × Angus crossbred beef cattle (25–26 months old) with different marbling grades (according to GB/T 29392-2022, based on the marbling richness of the longissimus dorsi muscle at the 12th–13th rib interface) were analyzed by RT-qPCR and Western blot, respectively. Additionally, PPARD was knocked down and overexpressed in bovine mammary epithelial cells to validate its effects on lipid-metabolism-related genes. The results showed that the mRNA levels of CD36, FATP1, PPARD, RXRA, RXRB, and PLIN2 were significantly higher (p < 0.01) in livers tissues from the A3 and A4 groups (high marbling) than in those from the A1 and A2 groups (low to moderate marbling). Western blot analysis revealed significantly higher PPARD protein expression in the A3 and A4 groups (high marbling) than that in the A1 and A2 groups (low to moderate marbling) (p < 0.05). It should be noted that the sample size of Group A4 is only 2, and the results of this group should be considered as a preliminary trend that needs to be validated with larger sample sizes. Cellular experiments confirmed that PPARD knockdown significantly decreased mRNA expressions of FABP1, CD36, and PLIN2 (p < 0.01), while PPARD overexpression significantly increased their mRNA levels (p < 0.05). These results indicate a positive correlation between PPARD expression and the transcriptional levels of genes involved in fatty acid transport and lipid droplet storage, suggesting that PPARD may be associated with hepatic lipid metabolism and potentially contribute to marbling development. These findings suggest that the PPARD signaling pathway contributes to hepatic lipid deposition and may play a role in marbling formation in beef cattle. Full article

(This article belongs to the Section Cattle)

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29 pages, 3075 KB

Open AccessArticle

Plasma Exosomes Associated with Growth Divergence in High-Density Cultured Grass Carp (Ctenopharyngodon idella): miRNA-Protein Profiling Reveals Cross-Tissue Communication Networks

by Tengfei Zhu, Zhipeng Zheng, Hao Chen, Yingying Yu, Huayang Guo, Baosuo Liu, Kecheng Zhu, Nan Zhang, Lin Xian, Shuhui Zheng, Yang Liu, Songlin Chen and Dianchang Zhang

Int. J. Mol. Sci. 2026, 27(13), 6059; https://doi.org/10.3390/ijms27136059 - 6 Jul 2026

Abstract

Grass carp (Ctenopharyngodon idella) is a major freshwater aquaculture species in China, but its growth is limited under intensive high-density farming. This study aimed to investigate the characteristics of plasma exosomes associated with distinct growth performance by isolating and characterizing exosomes from fast- and slow-growing grass carp after nine months of culture. Exosomes showed typical morphology and expressed characteristic markers (CD63, CD81, TSG101). Small RNA sequencing identified 3325 miRNAs, with 177 highly abundant miRNAs differentially expressed: immune-related miRNAs were upregulated, while development-inhibitory miRNAs were downregulated in fast-growing fish. Target gene enrichment highlighted pathways in neural and skeletal development and amino acid metabolism. Integrative analysis across tissues revealed 26 miRNAs with coordinated expression patterns between plasma exosomes and brain, liver, or muscle, validated by qPCR. DIA proteomics quantified 4203 proteins, identifying 843 differentially enriched proteins linked to immune response, energy metabolism, and endoplasmic reticulum stress. Notably, TYMP was upregulated in muscle and exosomes, while several proteins (e.g., GYG2, BHMT) showed coordinated downregulation across tissues and exosomes in large fish. These results provide comprehensive evidence of exosome-mediated cross-tissue communication in teleosts and suggest a potential role for plasma exosomal miRNAs and proteins as non-invasive biomarkers correlated with growth status in aquaculture. Full article

(This article belongs to the Section Molecular Biology)

20 pages, 8494 KB

Open AccessArticle

Genome-Wide Identification, Expression and Tissue-Specific Epigenetic Modification Analysis of the Su(var)3-9 SET Gene Family in Soybean

by Min Wang, Wei Zhou, Zihui Zhang, Lesheng Cao, Lishan Wang, Linan Xie, Junwei Wu, Haoce Xu and Ning Jia

Biology 2026, 15(13), 1085; https://doi.org/10.3390/biology15131085 - 6 Jul 2026

Abstract

Background: Su(var)3-9 SET genes encode key histone methyltransferases that catalyze H3K9 methylation, a modification generally associated with heterochromatin formation and transcriptional repression. Methods: We identified 23 GmSu(var)3-9 SETs and systematically characterized their tissue-specific epigenetic modifications as well as their phylogenetic relationships, chromosomal distributions, conserved domains, gene structures, GO annotations, collinearity, cis-regulatory elements, and expression profiles across diverse tissues and under salt stress. Results: These genes were divided into seven groups, exhibiting diverse structures and uneven distribution on chromosomes. Gene structure and conserved motif analyses revealed high structural diversity among family members, with variations in intron–exon distribution, conserved motifs, and functional domains. Promoter analysis detected multiple cis elements responsive to light, hormones, and abiotic stresses. Most genes showed preferential expression in meristems, roots, and leaves, and responded to salt stress. Co-expression network analysis revealed that these genes were co-expressed with stress- and development-related genes. GmSUVH12 histone modifications exhibited obvious tissue specificity. Conclusions: Overall, these results provided insights into the evolutionary and functional roles of GmSu(var)3-9 SETs in soybean. Full article

(This article belongs to the Special Issue The Potential of Genetics and Plant Breeding in Crop Improvement)

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26 pages, 720 KB

Open AccessReview

Imaging and Molecular Biomarkers of PFAS-Related Vascular Aging: A Narrative Review

by Andrea Borghini, Francesco Faita, Ludovica Simonini, Mariangela Palazzo, Cinzia Sagheddu, Chiara Cavigli, Gabriele Donzelli, Elisa Bustaffa, Stefano Masi, Francesca Gorini and Fabrizio Minichilli

Int. J. Mol. Sci. 2026, 27(13), 6064; https://doi.org/10.3390/ijms27136064 - 6 Jul 2026

Abstract

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants increasingly associated with cardiovascular disease. Identifying early manifestations of vascular aging before the onset of overt disease is essential for improving cardiovascular risk stratification and prevention. Emerging evidence suggests that PFAS exposure contributes to early vascular and atherosclerotic alterations detectable by imaging techniques, including increased carotid intima–media thickness (CIMT), arterial stiffness, and endothelial dysfunction. In contrast, evidence for associations with coronary artery calcium progression and coronary stenosis remains scarce. Mechanistically, PFAS exposure promotes endothelial dysfunction, oxidative stress, chronic inflammation, lipid dysregulation, and genetic and epigenetic modifications, all of which contribute to premature vascular aging and metabolic disturbances. The integration of imaging and molecular biomarkers may provide complementary insights into the structural, functional, and biological processes underlying PFAS-related vascular damage; however, to date, this field remains largely unexplored. This narrative review summarizes current evidence on imaging and molecular biomarkers of PFAS-induced vascular aging and discusses their potential role in cardiovascular risk assessment. It also highlights key knowledge gaps and the need for robust epidemiological and multi-omics studies to validate these biomarkers, clarify causal mechanisms, and support their application in cardiovascular and environmental health surveillance. Full article

(This article belongs to the Special Issue Cellular and Molecular Progression of Cardiovascular Diseases: 2nd Edition)

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30 pages, 519 KB

Open AccessReview

Mental Fatigue in Collegiate Athletes: A Behavioral Science Review of Stress Appraisal, Competitive Anxiety, and Resilience-Related Regulation

by Zihan Gao, Wan Ahmad Munsif Wan Pa and Mohamad Nizam bin Nazarudin

Behav. Sci. 2026, 16(7), 1133; https://doi.org/10.3390/bs16071133 - 6 Jul 2026

Abstract

Mental fatigue is an increasingly important concern among collegiate athletes whose academic–athletic roles require sustained cognitive effort, emotional regulation, and recovery across overlapping performance contexts. This structured narrative review synthesizes behavioral science, sport psychology, and athlete mental health literature to clarify how perceived stress, competitive anxiety, and psychological resilience may interact in the development and regulation of mental fatigue among collegiate athletes. Rather than treating mental fatigue as simple tiredness or an isolated performance symptom, this review conceptualizes it as a cognitive–emotional and psychobiological outcome shaped by stress appraisal, attentional load, effort regulation, and resource depletion. The main contribution of this review is to integrate previously separate lines of research into a collegiate-athlete-focused behavioral science framework in which perceived stress is positioned as an upstream appraisal-based condition, competitive anxiety as a proximal emotional mechanism, and psychological resilience as a dynamic regulatory resource that may buffer fatigue-related vulnerability. Tennis and Chinese/non-Western collegiate sport contexts are used as illustrative applications rather than exclusive empirical targets, highlighting how individual accountability, academic–athletic role demands, cultural expectations, and support structures may shape fatigue processes. This review also distinguishes established empirical evidence from theoretical inference and identifies key gaps in measurement heterogeneity, methodological transparency, longitudinal evidence, and culturally diverse collegiate athlete research. By refining the stress–anxiety–fatigue pathway and identifying resilience, recovery, and contextual support as important regulatory factors, this review provides a conceptual foundation for future empirical testing and for more targeted behavioral interventions to support collegiate athlete well-being and performance sustainability. Full article

(This article belongs to the Section Health Psychology)

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21 pages, 874 KB

Open AccessArticle

Positive Self-Perception of Aging and Quality of Life in People Living with HIV: The Role of Cultural Stereotype Internalization

by Ana Laguía, Antonio Bustillos, Cristina Moreno, Inmaculada Jarrín and María José Fuster-RuizdeApodaca

Healthcare 2026, 14(13), 2011; https://doi.org/10.3390/healthcare14132011 - 6 Jul 2026

Abstract

Introduction: Individuals aging with HIV face significant challenges that can negatively impact their long-term health, including biomedical complications, premature aging, and the influential role of aging-related stereotypes. Our study aimed to investigate whether a more positive self-perception of aging is associated with better health-related quality of life and less adverse impacts of premature aging on people living with HIV. Methods: We conducted a multicenter study combining a cross-sectional survey with a 2-year retrospective extraction of clinical data from medical records, involving 285 participants aged ≥ 50 years (77.9% male) living with HIV in Spain. Participants reported their health-related quality of life, self-perception of aging, and cultural age-related stereotypes. Additionally, two years of retrospective clinical health data were collected for eight areas: Metabolic, Neurological, Neoplastic, Bone, Hepatic, Renal, Cardiovascular, and Others. Results: As expected, worse physical health over the past two years had a negative impact on the self-perception of aging. Cultural age-related stereotypes of warmth and competence were found to predict their internalization into the self-concept. However, only self-perceived competence mediated the influence of the cultural age-related stereotype of the competence dimension on a more positive self-perception of aging. Furthermore, a positive self-perception of aging positively predicts all dimensions of health-related quality of life. Conclusions: Our data suggest two interrelated pathways that may influence the aging process: a clinical pathway, characterized by the negative impact of pre-existing comorbidities, and a psychosocial pathway, related to the internalization of cultural stereotypes. This study highlights the impact of cultural stereotypes on the self-perception of aging through their internalization in a sample of individuals experiencing premature aging. Full article

(This article belongs to the Special Issue HIV and Aging)

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22 pages, 885 KB

Open AccessArticle

Th2 and Th17/Th1 Inflammatory Profiles in Chronic Rhinosinusitis: Associations with Vitamin D Status and Disease Severity

by Agnieszka Witkowska-Janik, Andrzej Wojdas, Maria Sobol, Agata Pabin, Katarzyna Komar, Ewelina Maculewicz and Piotr Rot

Int. J. Mol. Sci. 2026, 27(13), 6061; https://doi.org/10.3390/ijms27136061 - 6 Jul 2026

Abstract

Vitamin D is believed to exert an immunomodulatory effect in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and may influence the intensity of inflammatory processes. Therefore, this study aimed to assess serum vitamin D levels in relation to selected cytokines in patients with CRSwNP and without nasal polyps (CRSsNP). This prospective study included patients with clinically and radiologically confirmed diseases. In total, 39 patients were included in three phenotypic groups: CRSwNP (n = 17), CRSsNP (n = 10), and controls (n = 12). Serum concentrations of vitamin D (25(OH)D3), interleukins 4, 5, 17A, interferon-γ (IFN-γ), and immunoglobulin E were assessed preoperatively. The extent of subjective and objective mucosal disease was evaluated using endoscopic and radiological staging, based on the Lund–Kennedy and Lund–Mackay scoring systems in accordance with the Sino-Nasal Outcome Test-22 (SNOT-22), respectively. Patients with CRSwNP demonstrated higher serum IL-4 and IL-5 concentrations, consistent with a Th2-skewed inflammatory profile, whereas patients with CRSsNP showed higher IL-17A and IFN-γ levels, suggesting a mixed Th17/Th1 inflammatory pattern. IL-5 was positively associated with radiological disease severity. Serum vitamin D levels tended to be inversely associated with IL-5 concentration and disease severity; however, these associations did not reach statistical significance.: The findings of this study support differences in inflammatory profiles between CRSwNP and CRSsNP and confirm an association between IL-5 and radiological disease severity. Although lower vitamin D levels showed a trend toward greater inflammatory activity and disease severity, no statistically significant associations were demonstrated in this cohort. Further studies with larger populations are warranted to clarify the role of vitamin D in CRS endotypes. Full article

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

33 pages, 3869 KB

Open AccessReview

A New Anatomy of Autophagic Clearance: On the Roles of Intrinsic Disorder in the Membrane-Less on Membrane-Encapsulated Mechanism

by Vladimir N. Uversky, Hana Popelka and Daniel J. Klionsky

Membranes 2026, 16(7), 234; https://doi.org/10.3390/membranes16070234 - 6 Jul 2026

Abstract

Autophagy is a carefully regulated catabolic process that utilizes assemblies of specific sets of macromolecules operating at multiple stages of the pathway. Discoveries in recent years show that autophagy markedly relies on liquid-liquid phase separation (LLPS). Here, we present parameters that indicate the plasticity of autophagy proteins and their probability to undergo LLPS in macroautophagy and microautophagy. We show that microautophagy is an extremely LLPS-friendly pathway. Several mechanisms involving proteins in the autophagy machinery that drive LLPS on various types of membranes to regulate this process or that undergo LLPS as autophagic cargo are described in detail. We also summarize the factors that modulate the LLPS potential of autophagy proteins. A high probability of autophagy-related proteins to undergo spontaneous LLPS shown here can direct future research on the role of protein droplets in autophagy. Full article

(This article belongs to the Special Issue Advances in Biomembrane Structure, Dynamics, and Function)

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37 pages, 2136 KB

Open AccessArticle

A Lightweight Zero-Trust Authentication and Key Agreement Scheme for the Industrial Internet of Things

by Xun Zhang, Zhiying Mu, Dejun Mu and Xin Liu

Appl. Sci. 2026, 16(13), 6765; https://doi.org/10.3390/app16136765 - 6 Jul 2026

Abstract

The Industrial Internet of Things (IIoT) demands authentication that protects resource-constrained field devices, supports fine-grained access control, and reduces reliance on implicitly trusted gateways. Existing IIoT authentication and key agreement schemes mainly verify cryptographic identity and establish session keys, but provide limited support for zero-trust access decisions after authentication such as role-specific operation control, gateway-side relation protection, emergency override, and context-aware re-verification. This paper proposes a lightweight zero-trust authentication and key agreement scheme for IIoT. The scheme embeds role-, device-, environment-, and behavior-aware control points into the authentication flow, protects gateway-side authentication relations and operator–asset mappings using secGear-based confidential computing, and supports pseudonym-based identity protection and break-the-glass emergency access. To complement deterministic access control, an optional auxiliary risk evaluation module provides trust evidence from contextual and operator-state signals without becoming part of the cryptographic critical path. This module is used to trigger re-verification, privilege degradation, audit escalation, or session termination before high-risk control privileges are released; it does not replace cryptographic authentication or constitute a formal guarantee of coercion detection, and the cryptographic layer remains fully functional and formally analyzable even when the auxiliary risk evaluation module is disabled. BAN logic and AVISPA analyses verify the cryptographic authentication and key agreement layer, while a comparative overhead analysis under an analytical operation count basis indicates low computation and communication cost relative to representative resource-constrained IoT authentication schemes. Full article

(This article belongs to the Special Issue Security, Privacy and Application in New Intelligence Techniques: 2nd Edition)

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23 pages, 335 KB

Open AccessArticle

Herding Behavior in Commodity Markets During Geopolitical Conflict: Evidence from the Iran Conflict Escalations (2024–2026)

by Ibrahim N. Khatatbeh, Jamil J. Jaber, Raneem Aldeki and Maher Khasawneh

Commodities 2026, 5(3), 15; https://doi.org/10.3390/commodities5030015 (registering DOI) - 6 Jul 2026

Abstract

Military conflict generates a qualitatively distinct category of market shock that is sudden, geographically concentrated, and channeled directly through physical energy supply routes. This paper examines investor herding and cross-sectional return dispersion across five commodity markets (Brent crude, WTI crude, Henry Hub natural gas, spot gold, and the Baltic Dry Index) using 475 daily observations from January 2024 through April 2026, covering the sustained escalation phase of the Iran–Israel conflict. The empirical analysis incorporates eight complementary specifications: (1) baseline CSAD regression; (2) GARCH(1,1) conditional volatility augmentation; (3) volatility regime partitioning (high versus low); (4) quantile regression across the CSAD distribution; (5) asset-level disaggregation; (6) interaction with the geopolitical risk (GPR) index; (7) asymmetric analysis distinguishing between up- and down-market conditions; and (8) rolling 240-day estimation to capture time-varying dynamics. The results tend to reject the herding hypothesis and provide suggestive evidence of positive cross-commodity dispersion. The baseline model shows that large market movements significantly increase cross-sectional dispersion. At the asset level, natural gas exhibits the highest dispersion coefficient, reflecting its structural independence from oil-related geopolitical fundamentals. Moreover, gold provides evidence consistent with a positive but comparatively smaller coefficient, consistent with its role as a stabilizing safe-haven asset. Dispersion effects are broadly symmetric across market conditions. Furthermore, the geopolitical risk index does not exert a significant marginal effect. However, the analysis is restricted to five commodity assets and a single geopolitical conflict episode (the Iran–Israel conflict), which may limit the generalizability of the findings to other markets or conflict contexts. Full article

30 pages, 2663 KB

Open AccessReview

Dendritic Cells as Immunometabolic Regulatory Nodes in Diabetes: Molecular Mechanisms and Therapeutic Reprogramming

by Fangfang Jin, Weidong Wu, Xuan Yang, Xiang Fan, Xiaosen Zhao, Wei Liu and Xinrong Fan

Int. J. Mol. Sci. 2026, 27(13), 6057; https://doi.org/10.3390/ijms27136057 - 6 Jul 2026

Abstract

Diabetes mellitus comprises a group of heterogeneous metabolic disorders characterized by persistent hyperglycemia, progressive β-cell dysfunction, and multi-organ complications. Although type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have distinct pathogenic origins, both involve immune dysregulation, tissue stress, release of danger signals, and chronic inflammation. Dendritic cells (DCs), as antigen-presenting cells, integrate innate immune sensing, antigen presentation, cytokine production, T-cell regulation, and peripheral immune tolerance, placing them at a critical interface between autoimmunity and metabolic inflammation. In T1DM, DCs contribute to β-cell autoantigen presentation, tolerance breakdown, autoreactive T-cell activation, and insulitis amplification. In T2DM, DCs may contribute to adipose tissue inflammation, hepatic immunometabolic crosstalk, β-cell stress, vascular inflammation, and immune remodeling associated with diabetes-related complications. Here, we review the disease-specific roles of DC subsets in T1DM and T2DM and discuss shared molecular mechanisms, including pattern-recognition receptor signaling, metabolic reprogramming, inflammasome activation, cytokine networks, and the shift from immune tolerance to inflammation. We also evaluate therapeutic DC reprogramming strategies and their potential implications for targeted immunometabolic intervention in diabetes. Full article

(This article belongs to the Special Issue Latest Advances in Diabetes Research and Practice)

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17 pages, 25404 KB

Open AccessArticle

FAK and Pyk2: Paralogous Kinases with Opposing Roles in Vasculogenic Mimicry in Triple-Negative Breast Cancer

by Shilpa Madhavan-Kadali, Tal Sneh, Naamah Bloch, Joseph D. Rosenblatt, Abraham O. Samson and Hava Gil-Henn

Int. J. Mol. Sci. 2026, 27(13), 6053; https://doi.org/10.3390/ijms27136053 - 6 Jul 2026

Abstract

Vasculogenic mimicry (VM) is a non-endothelial mode of tumor vascularization in which aggressive cancer cells form vessel-like networks that support microcirculation, metastasis, and resistance to anti-angiogenic therapies. VM is particularly prominent in triple-negative breast cancer (TNBC), but its molecular regulators remain incompletely understood. Focal adhesion kinase (FAK) and its paralog, proline-rich tyrosine kinase 2 (Pyk2), are closely related non-receptor tyrosine kinases implicated in epithelial-to-mesenchymal transition (EMT), invasion, and metastasis in TNBC. However, their roles in VM have not been defined. Here we perform transcriptomic analysis of FAK and Pyk2 clinical expression patterns using TNMplot V2, DepMap, and patient cohort datasets to systematically dissect the distinct contributions of FAK and Pyk2 to VM in TNBC. Our in vitro tube formation assay shows that in TNBC cells, knockdown of FAK, but not Pyk2, results in failure to form robust 3D vessel-like networks in Matrigel. Similarly, overexpression of Pyk2, but not FAK, in TNBC cells results in poor vessel-like network formation. Consistent with these findings, analysis of two independent patient cohorts (TCGA-BRCA and METABRIC) revealed selective upregulation of FAK in TNBC, while Pyk2 was inversely associated with vasculogenic-mimicry-associated gene expression, supporting the opposing roles of the two kinases in patient tumors. Taken together, these findings establish that FAK and Pyk2 govern VM through non-redundant, kinase-specific, and functionally opposed mechanisms: FAK acting as a positive regulator of VM, and Pyk2 as a context dependent suppressor of VM at elevated levels. These results nominate FAK as a candidate target for suppressing VM-driven tumor perfusion in TNBC and suggest that dual FAK/Pyk2 inhibition warrants caution hypotheses that remain to be tested pharmacologically. Full article

(This article belongs to the Section Molecular Oncology)

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