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27 pages, 8969 KB  
Article
Pan-Cancer Bioinformatics-Guided Evaluation of San-Huang-Xie-Xin-Tang Identifies Kidney Renal Clear Cell Carcinoma as a Potentially Responsive Cancer Type
by Syu-You Zuo, Yu-Pao Chou, Tai-Hsuan Hsu, Jan-Gowth Chang and Wen-Ling Chan
Pharmaceuticals 2026, 19(6), 936; https://doi.org/10.3390/ph19060936 (registering DOI) - 14 Jun 2026
Abstract
Background/Objectives: San-Huang-Xie-Xin-Tang (SHXXT) is a classical traditional Chinese herbal formula composed of Coptis chinensis, Scutellaria baicalensis, and Rheum palmatum, with documented anti-inflammatory and anticancer properties. Despite growing interest in its pharmacological potential, systematic evaluation of its gene regulatory effects across [...] Read more.
Background/Objectives: San-Huang-Xie-Xin-Tang (SHXXT) is a classical traditional Chinese herbal formula composed of Coptis chinensis, Scutellaria baicalensis, and Rheum palmatum, with documented anti-inflammatory and anticancer properties. Despite growing interest in its pharmacological potential, systematic evaluation of its gene regulatory effects across multiple cancer types remains limited. This study aimed to assess the prognostic relevance of SHXXT-regulated genes across pan-cancer contexts using publicly available transcriptomic and clinical datasets. Methods: Fifteen active compounds of SHXXT were identified from traditional Chinese medicine databases (Encyclopaedia of Traditional Chinese Medicine (ETCM) 2.0, Chinese Compound Medicine Database (ccTCM), and Integrated Traditional Chinese Medicine Database (ITCM)). Compound-induced gene expression profiles were obtained from MCF7-based transcriptomic perturbation data in the ITCM database and integrated with The Cancer Genome Atlas (TCGA) across 24 cancer types. Survival-associated genes were evaluated using Cox proportional hazards regression and Kaplan–Meier analysis. A weighted prognostic scoring framework, supported by normalization and sensitivity analyses, was developed to prioritize cancer types according to the concordance between SHXXT-induced gene regulation and favorable prognostic patterns. Functional enrichment analysis was performed using Annotation, Visualization, and Integrated Discovery (DAVID), and cancer-related genes were annotated using the OncoKB database. Complementary in vitro studies, including Annexin V/propidium iodide (PI) and MT-1 staining assays, were conducted in Hep3B cells using a Good Manufacturing Practice (GMP)-certified commercial SHXXT preparation. Results: SHXXT-regulated genes were significantly enriched in cancer-related pathways, particularly the PI3K–Akt and MAPK signaling pathways. Pan-cancer analysis revealed substantial heterogeneity in prognostic alignment across cancer types. Among the 24 cancer cohorts analyzed, kidney renal clear cell carcinoma (KIRC) achieved the highest prognostic alignment score within the proposed framework. In KIRC, several genes, including PIK3CA, PIK3CB, KRAS, and RAF1, remained significantly associated with favorable prognostic alignment after multivariable adjustment. Pathway enrichment analysis further identified PI3K–Akt and MAPK signaling as the most significantly represented pathways among favorably aligned genes. In contrast, hepatocellular carcinoma exhibited a relatively low prognostic alignment score, consistent with in vitro observations indicating predominantly non-selective cytotoxic stress rather than cancer-specific therapeutic activity. Conclusions: SHXXT-regulated genes exhibited marked heterogeneity across cancer types, with KIRC was consistently prioritized as the top-ranked cancer type across multiple analytical scenarios, suggesting a strong concordance between SHXXT-associated gene regulation and favorable prognostic signatures. These findings represent computational predictions derived from transcriptomic and survival associations rather than direct evidence of therapeutic efficacy. The study provides a reproducible pan-cancer strategy for prioritizing candidate cancer types for future mechanistic and experimental validation of traditional Chinese medicine formulations. Full article
(This article belongs to the Special Issue Cancer Therapeutics: Drug Repurposing and Computational Strategies)
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22 pages, 1729 KB  
Review
Retinoic Acid Signaling in Male Reproductive Biology: From Germ Cell Regulation to Contraceptive Innovation Within a One Health Framework
by Vanmathy Kasimanickam and Ramanathan Kasimanickam
Animals 2026, 16(12), 1831; https://doi.org/10.3390/ani16121831 (registering DOI) - 14 Jun 2026
Abstract
Spermatogenesis is a highly coordinated biological process in which diploid spermatogonia undergo mitotic expansion, meiotic division, and terminal differentiation into haploid spermatozoa. This process is tightly regulated by intrinsic germ cell programs and extrinsic signals from Sertoli cells within the seminiferous epithelium. Among [...] Read more.
Spermatogenesis is a highly coordinated biological process in which diploid spermatogonia undergo mitotic expansion, meiotic division, and terminal differentiation into haploid spermatozoa. This process is tightly regulated by intrinsic germ cell programs and extrinsic signals from Sertoli cells within the seminiferous epithelium. Among the signaling pathways governing male germ cell development, all-trans retinoic acid (RA), a bioactive metabolite of vitamin A, has emerged as a master regulator of meiotic initiation and spermatogonial differentiation in mammals. RA functions through nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which regulate transcriptional networks essential for germ cell progression, including the activation of Stimulated by Retinoic Acid 8 (STRA8), a key determinant of meiotic entry. Intratesticular RA homeostasis is maintained by a balance between synthesis via aldehyde dehydrogenase (ALDH) enzymes and degradation by cytochrome P450 family 26 (CYP26) enzymes, ensuring precise temporal and spatial control of germ cell development. While rodent models have defined core mechanisms of RA signaling, the canine testis provides a valuable comparative and translational system due to its physiological similarity to human spermatogenesis and relevance to reproductive management. Recent studies highlight conserved RA signaling pathways in dogs, including receptor-mediated transcriptional regulation, feedback control of RA metabolism, and post-transcriptional modulation via microRNAs. Importantly, pharmacological manipulation of RA signaling can reversibly disrupt spermatogenesis, supporting its potential applications in non-hormonal male contraception. This review integrates molecular, developmental, pharmacological, and comparative evidence and presents RA signaling as a central regulatory axis of spermatogenesis with important translational applications. Full article
(This article belongs to the Section Animal Reproduction)
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26 pages, 4419 KB  
Article
Regulatory Gap in Fenestration Thermal Performance: Integrating Linear Thermal Transmittance into Energy Codes
by Muhammad Tayyab Naqash and Antonio Formisano
Sustainability 2026, 18(12), 6111; https://doi.org/10.3390/su18126111 (registering DOI) - 14 Jun 2026
Abstract
Fenestration systems play a critical role in building thermal performance, particularly in cooling-dominated climates where envelope inefficiencies directly amplify electricity demand. In Saudi Arabia and other Gulf Cooperation Council (GCC) countries, cooling accounts for the majority of building energy consumption. Nevertheless, the facade [...] Read more.
Fenestration systems play a critical role in building thermal performance, particularly in cooling-dominated climates where envelope inefficiencies directly amplify electricity demand. In Saudi Arabia and other Gulf Cooperation Council (GCC) countries, cooling accounts for the majority of building energy consumption. Nevertheless, the facade and insulated glass industries are experiencing rapid market expansion. Despite this technological evolution, prevailing regulatory frameworks, including the Saudi Building Code Energy Conservation Requirements (SBC 601), ASHRAE 90.1, and the International Energy Conservation Code (IECC), primarily rely on area-weighted U-values and solar heat gain coefficients (SHGCs) without explicitly integrating multidimensional thermal bridge effects such as linear thermal transmittance (ψ). This paper examines the omission of ψ from current energy compliance systems, evaluates its implications in cooling-dominated climates, and proposes a phased regulatory integration pathway aligned with sustainability objectives under Vision 2030. Literature reports indicate that thermal bridges may increase cooling loads by up to 25% and total building energy use by 5–30%, depending on climate severity and façade configuration. The findings highlight the need to transition from simplified prescriptive compliance toward a physics-informed governance capable of addressing evolving facade complexity in hot-arid environments. The proposed framework offers a systematic pathway for integrating linear thermal transmittance requirements while supporting regional sustainability goals and advancing high-performance building technologies. Full article
(This article belongs to the Section Sustainable Engineering and Science)
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16 pages, 3940 KB  
Article
Co-Analysis of Transcriptome and Metabolome Reveals Anthocyanin Accumulation in the Female Flower Tissues of Fig Cultivar ‘Silu Hongyu’
by Ying Zhang, Yuqin Jiang, Shuanti Qian, Siyu Jing, Zijin Liu and Zhihao Zhao
Genes 2026, 17(6), 694; https://doi.org/10.3390/genes17060694 (registering DOI) - 14 Jun 2026
Abstract
Background/Objectives: Fig (Ficus carica L.) is considered a valuable fruit owing to its rich health-promoting ingredients, including anthocyanins. However, little information is available on the regulatory networks that reveal anthocyanin biosynthesis in figs, especially the new fig cultivar “Silu Hongyu” (HY). Methods: [...] Read more.
Background/Objectives: Fig (Ficus carica L.) is considered a valuable fruit owing to its rich health-promoting ingredients, including anthocyanins. However, little information is available on the regulatory networks that reveal anthocyanin biosynthesis in figs, especially the new fig cultivar “Silu Hongyu” (HY). Methods: In this study, multi-omics analysis was performed to dissect the regulatory networks responsible for anthocyanin accumulation in the female flower tissues of HY. Results: we found that the anthocyanin content in the female flower tissues of HY is higher than that of “Chinese Ziguo” (ZG). Metabolomic profiling identified 350 differentially accumulated metabolites (DAMs), among which 108 were flavonoids. The contents of multiple metabolites responsible for anthocyanin accumulation, such as naringenin chalcones, cyanidin 3-glucoside, and pelargonidin 3,5-diglucoside, were significantly increased in the HY female flower tissues. Transcriptomic analysis revealed that 3696 differentially expressed genes (DEGs) were screened from the female flower tissues of ZG and HY, with 1730 upregulated DEGs and 1966 downregulated DEGs in HY compared to ZG. The key structural genes involved in anthocyanin biosynthesis, including FcPAL, Fc4CL, FcCHS, FcF3′H, and FcBZ1, were significantly upregulated in the female flower tissues of HY compared with ZG. KEGG analysis also demonstrated that five flavonoid biosynthesis pathways were co-enriched by DAMs and DEGs. Conclusion: These findings provide a multi-omics framework that governs anthocyanin biosynthesis in the female flower tissues of HY, which will facilitate the genetic breeding and improvement of high-anthocyanin fig cultivars. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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19 pages, 4790 KB  
Article
Biphasic Responses of Porcine Oocytes to Metformin: Concentration-Dependent AMPK Activation and Nrf2-Mediated Antioxidant Regulation
by Junyu Wang, Min Li, Yaqi Zhou, Fuyin Fu, Feng Liu, Jinghe Tan, Mingjiu Luo and Shuai Gong
Animals 2026, 16(12), 1828; https://doi.org/10.3390/ani16121828 (registering DOI) - 13 Jun 2026
Abstract
Metformin (MET) plays crucial regulatory roles in mammalian oocyte meiosis, yet the concentration-dependent biphasic impacts of MET on porcine oocyte in vitro maturation (IVM) and the related molecular mechanisms remain poorly clarified. This study aimed to explore the distinct effects and underlying pathways [...] Read more.
Metformin (MET) plays crucial regulatory roles in mammalian oocyte meiosis, yet the concentration-dependent biphasic impacts of MET on porcine oocyte in vitro maturation (IVM) and the related molecular mechanisms remain poorly clarified. This study aimed to explore the distinct effects and underlying pathways of low- and high-dose MET in porcine oocytes. Different concentrations of MET (0, 7.5, 15, 30, 150, and 300 μM) were supplemented during oocyte IVM, with phenotypic detection, untargeted metabolomic analysis, and Nrf2 inhibitor (ML385) intervention performed for mechanism exploration. Results showed that 15 μM low-dose MET facilitated oocyte maturation, mitochondrial function and redox balance, while 300 μM high-dose MET caused obvious developmental damage. Mechanistically, low-dose MET triggered noncanonical AMPK activation independent of the AMP/ATP ratio and enhanced AMPK–Nrf2 antioxidant signaling, whereas high-dose MET induced energy stress and oxidative injury via inhibiting mitochondrial complex I. Blockade of Nrf2 further abolished the protective effects of low-dose MET. Collectively, this finding illustrates the biphasic actions of MET on porcine oocytes and provides a theoretical reference for optimizing porcine in vitro embryo production. Full article
(This article belongs to the Special Issue Advances in Pig Reproductive Physiology)
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27 pages, 3257 KB  
Review
Exercise Adaptation as an Immunometabolic Process: A Systems-Level Perspective on NLRP3 Inflammasome Activation and PPARD-Mediated Metabolic Signaling
by Carlos Andrés Restrepo-Pardo, Jenny Lorena Mejia-Idarraga, Luisa Matilde Salamanca-Duque, Zarita Naranjo-Gutierrez and Carlos Andrés Naranjo-Galvis
Physiologia 2026, 6(2), 42; https://doi.org/10.3390/physiologia6020042 (registering DOI) - 13 Jun 2026
Abstract
Background: Exercise adaptation is increasingly recognized as an immunometabolic process driven by coordinated interactions among inflammatory signaling, mitochondrial regulation, metabolic homeostasis, and recovery-associated physiology. Within this framework, NLRP3 inflammasome activation and PPARD-mediated metabolic signaling have emerged as biologically relevant pathways potentially involved [...] Read more.
Background: Exercise adaptation is increasingly recognized as an immunometabolic process driven by coordinated interactions among inflammatory signaling, mitochondrial regulation, metabolic homeostasis, and recovery-associated physiology. Within this framework, NLRP3 inflammasome activation and PPARD-mediated metabolic signaling have emerged as biologically relevant pathways potentially involved in exercise-induced physiological adaptation. However, the contribution of regulatory genetic variations linking these pathways remains poorly characterized. Objective: To synthesize current evidence regarding the integration of NLRP3- and PPARD-related pathways in exercise immunometabolism and adaptive physiological responses to exercise, with particular emphasis on the regulatory variants NLRP3 rs10754558 and PPARD rs2267668 as potential contributors to interindividual variability in exercise adaptation. Methods: A structured narrative review complemented by exploratory systems-level in silico analyses was conducted using the PubMed, Scopus, and Web of Science databases until March 2026. Evidence related to exercise physiology, inflammatory regulation, metabolic adaptation, and exercise-associated phenotypes involving the NLRP3 and PPARD pathways was evaluated. Complementary analyses included functional annotation, protein–protein interaction network analysis, and pathway enrichment using STRING, Reactome, KEGG, Gene Ontology, and other publicly available genomic databases. Particular attention was given to the functional and regulatory context of rs10754558 and rs2267668 within the interconnected inflammatory and metabolic pathways relevant to exercise adaptation. Results: The reviewed evidence identified recurrent interactions among the inflammatory and metabolic pathways involved in exercise adaptation and recovery. NLRP3 rs10754558 and PPARD rs2267668 were identified as candidate regulatory variants potentially positioned at the interface between inflammatory responsiveness and metabolic flexibility, providing a biologically plausible framework for understanding the interindividual variability in exercise adaptation. Exploratory system-level analyses identified recurrent associations among inflammatory signaling, mitochondrial function, energy-sensing pathways, and metabolic regulation. These findings primarily reflect the functional annotations and system-level pathway associations identified through exploratory analyses. Conclusions: Current evidence supports a systems-level physiological framework in which inflammatory and metabolic pathways interact dynamically during exercise adaptation and recovery. NLRP3- and PPARD-related pathways, including the candidate regulatory variants rs10754558 and rs2267668, may contribute to interindividual variability in exercise-associated physiological responses and represent promising targets for future hypothesis-driven investigations in exercise immunometabolism, exercise genomics and precision exercise medicine. Full article
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32 pages, 31352 KB  
Article
Dysregulation of the HSF1-Mediated UPRmt Pathway in Colonic Smooth Muscle Cells Drives Motility Dysfunction in Functional Constipation
by Junpeng Yao, Wen Wang, Wei Zhang, Hang Dong, Yujun Hou, Qianhua Zheng, Ying Li and Fang Zeng
Biomolecules 2026, 16(6), 868; https://doi.org/10.3390/biom16060868 (registering DOI) - 12 Jun 2026
Abstract
Mitochondrial dysfunction in colonic smooth muscle cells (SMCs) is closely associated with impaired gut motility in functional constipation (FC), but the underlying molecular mechanisms remain incompletely understood. The mitochondrial unfolded protein response (UPRmt) is a critical pathway for maintaining mitochondrial proteostasis, [...] Read more.
Mitochondrial dysfunction in colonic smooth muscle cells (SMCs) is closely associated with impaired gut motility in functional constipation (FC), but the underlying molecular mechanisms remain incompletely understood. The mitochondrial unfolded protein response (UPRmt) is a critical pathway for maintaining mitochondrial proteostasis, and heat shock factor 1 (HSF1) acts as an important upstream regulator of this response. In the present study, we employed a loperamide-induced FC mouse model, combined with single-cell transcriptomic, molecular, and functional analyses to characterize the HSF1-UPRmt pathway in colonic SMCs and to investigate its role in FC. Single-cell transcriptomic analysis of colon tissue from FC mice revealed marked downregulation of UPRmt-associated genes in colonic SMCs. Immunofluorescence, Western blotting, and RT-qPCR analyses of colonic tissue confirmed that HSF1 expression was reduced in colonic SMCs, along with the downregulation of the UPRmt components, including HSP60, mtHSP70, and LONP1. These molecular changes were accompanied by mitochondrial structural damage, seen by transmission electron microscopy, and by functional impairments, including reduced mitochondrial membrane potential, elevated mtROS production, decreased ATP levels, and diminished activities of respiratory chain complexes I–V. AAV9-mediated overexpression of HSF1 reactivated the UPRmt pathway, improved mitochondrial function, and ameliorated constipation, whereas shRNA-mediated knockdown of HSF1 further suppressed UPRmt activity and aggravated mitochondrial damage, indicating that HSF1 bidirectionally regulates this pathway. Complementary experiments in primary colonic SMCs confirmed that this regulatory mechanism operates in a cell-autonomous manner, as modulation of HSF1 expression produced corresponding changes in the UPRmt pathway, in the expression of mitochondrial respiratory chain complex subunits (ATP5A, NDUFA9, COX1, SDHA, UQCRC1), and in ATP production, mirroring the in vivo findings. Collectively, these results demonstrate that HSF1 plays a pivotal role in maintaining mitochondrial homeostasis in colonic SMCs through regulation of the UPRmt pathway and that HSF1 dysfunction is closely associated with slowed gut motility in FC. These findings offer a new mechanistic perspective on FC and point to the HSF1–UPRmt axis as a potential therapeutic target. Full article
(This article belongs to the Special Issue Mitochondria as a Target for Tissue Repair and Regeneration)
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24 pages, 4996 KB  
Review
The Role and Therapeutic Potential of the STING Signaling Pathway in the Pathogenesis of Diabetic Nephropathy
by Xin-Yuan Zhang, Yan Hu and Ming-Tan Tang
Pharmaceuticals 2026, 19(6), 927; https://doi.org/10.3390/ph19060927 (registering DOI) - 12 Jun 2026
Abstract
Diabetes mellitus currently represents a major public health burden worldwide. Among diabetic individuals, diabetic nephropathy (DN) is a frequent and serious microvascular complication that markedly affects both patients’ quality of life and clinical outcomes. DN has also emerged as the leading contributor to [...] Read more.
Diabetes mellitus currently represents a major public health burden worldwide. Among diabetic individuals, diabetic nephropathy (DN) is a frequent and serious microvascular complication that markedly affects both patients’ quality of life and clinical outcomes. DN has also emerged as the leading contributor to end-stage renal disease (ESRD). Over recent years, the stimulator of interferon genes (STING) signaling pathway (an essential element of the innate immune system) has drawn substantial research interest because of its involvement in inflammation and cell injury. This article reviews the fundamental mechanisms of the STING pathway and its regulatory functions in the pathogenesis of DN, with a focus on how the STING pathway mediates inflammatory responses, apoptosis, and fibrosis in diabetic renal tissues. Additionally, combining the latest findings from preclinical and clinical research, we discuss potential therapeutic strategies targeting the STING pathway. Beyond traditional STING inhibitor therapies, we highlight the emerging field of precision medicine for DN, summarizing recent research achievements in gene intervention, such as CRISPR-based gene editing, RNA interference (RNAi) technologies, and combination therapy strategies. Distinct from prior reviews, this work discusses the emerging concept that STING may function as a molecular hub connecting inflammation, fibrosis, and cell death in DN, while emphasizing that this concept is mainly supported by preclinical and early human observational evidence. Through this comprehensive review, we aim to enhance our understanding of the role of the STING signaling pathway in DN, identify novel therapeutic targets, and provide theoretical perspectives for the prevention and treatment strategies that require further clinical validation. Full article
(This article belongs to the Section Pharmacology)
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28 pages, 6818 KB  
Article
Insurance as a Scope 3 Climate Lever: Reframing EV Underwriting in the Sustainability Transition
by Haigang Zhuang, Jian Liu, Xiaodan Lin, Chen-Ying Lee and Chiangku Fan
Sustainability 2026, 18(12), 6047; https://doi.org/10.3390/su18126047 (registering DOI) - 12 Jun 2026
Abstract
The role of financial institutions in climate governance is increasingly being recognized, particularly in relation to Scope 3 emissions. While existing research has focused primarily on lending and investment activities, the potential influence of insurance operations on lifecycle emissions remains underexplored. This study [...] Read more.
The role of financial institutions in climate governance is increasingly being recognized, particularly in relation to Scope 3 emissions. While existing research has focused primarily on lending and investment activities, the potential influence of insurance operations on lifecycle emissions remains underexplored. This study examines electric vehicle (EV) insurance underwriting as a form of indirect climate governance, with particular attention being paid to claim-related decision processes that affect repair-, replacement-, and battery-related outcomes. A decision-analytical, scenario-based portfolio model is developed to analyze how underwriting and claims parameters may influence lifecycle emissions exposure. The model incorporates literature-informed and scenario-based parameter ranges derived from the lifecycle assessment literature and industry-relevant assumptions, while explicitly accounting for regulatory, technical, and behavioral constraints that limit insurer decision making. An exposure-based attribution framework is applied to link insurance-mediated outcomes to emissions associated with vehicle and battery manufacturing. The results suggest that claim-related parameters—particularly total-loss probability—are associated with variations in modeled emissions exposure within the analytical framework. Scenario analysis indicates that, under plausible parameter configurations, differences in claims decision structures may contribute to variation in lifecycle emissions at the portfolio level. Sensitivity analysis further indicates that these relationships appear stable across a range of parameter assumptions. The findings should be interpreted as scenario-based insights rather than empirical estimates, highlighting potential pathways through which insurance operations may influence emissions outcomes within existing constraints. The study contributes to the literature by extending Scope 3 governance analysis to insurance and by proposing an operational framework for interpreting insurance-associated emissions in lifecycle terms. Full article
(This article belongs to the Section Economic and Business Aspects of Sustainability)
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36 pages, 8722 KB  
Article
Environmental Exposure and Bioaccumulation of Potentially Toxic Elements in Fishery Resources from the Romanian Black Sea and Implications for Seafood Safety
by Andra Oros, Mădălina Galațchi and George Țiganov
Environments 2026, 13(6), 336; https://doi.org/10.3390/environments13060336 (registering DOI) - 12 Jun 2026
Abstract
Potentially toxic elements (PTE) are persistent contaminants in coastal systems and may accumulate in marine organisms, with relevance for both environmental monitoring and seafood safety assessment. This study provides an exploratory cross-biota assessment of Cd, Cr, Cu, Ni, and Pb in fishery resources [...] Read more.
Potentially toxic elements (PTE) are persistent contaminants in coastal systems and may accumulate in marine organisms, with relevance for both environmental monitoring and seafood safety assessment. This study provides an exploratory cross-biota assessment of Cd, Cr, Cu, Ni, and Pb in fishery resources from the Romanian Black Sea in 2024. The dataset included 24 composite samples and 120 analyte-level observations across bivalves, gastropods, pelagic fish, and demersal fish. Tissue concentrations were integrated with regulatory maximum levels, bioconcentration factors (BCF), biota–sediment accumulation factors (BSAF), and adult dietary risk indices, including estimated daily intake (EDI), target hazard quotient (THQ), and total target hazard quotient (TTHQ). Within the limits of this single-year dataset, Cd and Pb concentrations were generally higher in bivalves than in fish and gastropods, whereas Cr showed higher values in several fish samples, particularly pelagic fish. Cd was the main element of concern, with regulatory exceedances occurring mainly in bivalves and fewer exceedances in pelagic fish, while Pb exceedance was isolated. BCF and BSAF supported the relevance of Cd as a priority element but were interpreted only as descriptive tissue–water and tissue–sediment ratios, not as evidence of specific uptake pathways. Low abiotic Cd concentrations may have inflated some ratio-based values, and Cr interpretation remains limited by the absence of Cr speciation and dissolved/particulate partitioning data. The adult dietary risk assessment did not indicate substantial non-carcinogenic concern, as all individual THQ values and cumulative TTHQ values remained below 1. Overall, the findings support continued PTE monitoring in the Romanian Black Sea, using sessile bivalves as indicators of local environmental contamination and including gastropods and representative pelagic and demersal fish species of ecological and fisheries relevance to capture contaminant patterns across benthic and mobile fishery resources. Future monitoring should improve species-level replication, integrate metal partitioning in abiotic matrices, and include additional contaminants of seafood safety relevance, particularly Hg and As. Full article
(This article belongs to the Special Issue Environmental Pollution Exposure and Its Human Health Risks)
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30 pages, 699 KB  
Article
Configurational Pathways to Digital Traceability Success in International Trade: An fsQCA Study of Trade-Corridor Cases
by Hai Phu Do, Bui Kim Thuy and Nguyen Quoc Dung
Sustainability 2026, 18(12), 6045; https://doi.org/10.3390/su18126045 - 12 Jun 2026
Abstract
Digital traceability has become an important capability in international trade, especially in high-regulation and high-risk supply chains. However, existing research has not fully explained how institutional, technological, and coordination-related conditions combine to produce successful outcomes. This study applies fuzzy-set Qualitative Comparative Analysis (fsQCA) [...] Read more.
Digital traceability has become an important capability in international trade, especially in high-regulation and high-risk supply chains. However, existing research has not fully explained how institutional, technological, and coordination-related conditions combine to produce successful outcomes. This study applies fuzzy-set Qualitative Comparative Analysis (fsQCA) to 24 trade-corridor/product-chain cases to identify the configurational drivers of Digital Traceability Success (DTS). The findings show that Digital Trade Readiness (DTR), Market Strictness (MKT), Digital Infrastructure (DIF), and Cross-border Coordination (COO) are highly consistent necessary conditions for DTS, whereas Blockchain-enabled Traceability (BCT) is not. The sufficiency analysis identifies one dominant pathway, DTR * PRK * MKT * DIF * COO, with perfect consistency and substantial coverage. These results indicate that traceability success emerges from the alignment of institutional readiness, regulatory pressure, infrastructural capacity, product-related risk, and cross-border coordination rather than from blockchain adoption alone. The study contributes to digital trade and supply-chain governance literature by offering a configurational explanation grounded in conjunctural causation and causal asymmetry. It also clarifies blockchain’s role as a contingent enabling component rather than a universally necessary determinant. Practically, the findings suggest that policymakers and firms should prioritize interoperable infrastructure, institutional readiness, and cross-border governance mechanisms over stand-alone technological solutions. Full article
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17 pages, 281 KB  
Article
Reframing Lifelong Learning in Higher Education: Recognition, Care, and Civic Welfare
by Emanuela Proietti
Soc. Sci. 2026, 15(6), 384; https://doi.org/10.3390/socsci15060384 - 12 Jun 2026
Abstract
This paper offers a theoretical-interpretive contribution to the sociology of lifelong learning (LLL), exploring a sociological reframing of lifelong learning through the concept of social love as an analytical framework for reading the institutional practices of universities in the domain of LLL. Drawing [...] Read more.
This paper offers a theoretical-interpretive contribution to the sociology of lifelong learning (LLL), exploring a sociological reframing of lifelong learning through the concept of social love as an analytical framework for reading the institutional practices of universities in the domain of LLL. Drawing on classical and contemporary sociological traditions (including recognition theory, French pragmatic sociology, and relational sociology), the paper develops the argument that lifelong learning, when understood as a relational and generative practice, can be interpreted through the four dimensions of social love: overabundance, care, recognition, and universalism. The paper proposes what can be interpreted as a theoretical and educational transposition of the World Love Index (WLI) framework: a shift in scale, from the nation-state to the university, and in domain, from general social policy to educational practice, that preserves the core logic of the WLI while adapting it to the context of higher education. This transposition responds to a gap explicitly identified within the WLI research program and contributes to the debate on the civic and relational dimensions of higher education. Empirically, the paper draws on a national survey conducted within the Italian University Network for Lifelong Learning (RUIAP), which mapped lifelong learning services across 27 universities between 2022 and 2023. The survey data are used not as a basis for hypothesis testing but as exploratory empirical material through which to illustrate and develop the proposed framework, following a logic of theory elaboration. The findings reveal a heterogeneous and evolving system, characterized by uneven levels of institutionalization across the four dimensions: recognition practices are most widely present, though concentrated on formal pathways; care emerges in dedicated services for vulnerable and non-traditional populations; universalism remains largely unrealized in terms of territorial outreach; and overabundance (institutional investment exceeding regulatory compliance) is present in limited but analytically significant cases. The study concludes that understanding LLL as a practice of social love offers new insights into the civic mission of universities and their contribution to fostering social cohesion and democratic participation. It further proposes the need for observatories of institutional social love in higher education (such as RUIAP) and identifies directions for future research and policy oriented toward the generation of relational goods and the common good within university systems. Full article
22 pages, 4644 KB  
Article
Transcriptomic Analysis and Physiological Indicators Synthetically Uncover Candidate Genes Regulating Polyembryony Formation of Phoebe bournei Seeds
by Guoxin Mei, Lulu Wan, Zeping Jian, Baiyou Chen, Xiaowen Li, Bao Liu, Jun Xiong, Shipin Chen and Haichao Hu
Biology 2026, 15(12), 919; https://doi.org/10.3390/biology15120919 (registering DOI) - 12 Jun 2026
Abstract
Phoebe bournei is a precious timber species unique to China, possessing significant ornamental, ecological, and medicinal values. The polyembryonic phenomenon is widely observed in its seeds, but the underlying mechanisms driving its formation remain unclear. In this study, an integrated analysis was conducted [...] Read more.
Phoebe bournei is a precious timber species unique to China, possessing significant ornamental, ecological, and medicinal values. The polyembryonic phenomenon is widely observed in its seeds, but the underlying mechanisms driving its formation remain unclear. In this study, an integrated analysis was conducted for polyembryony formation in P. bournei seeds, including biochemical indicators, environmental factors, and transcriptional levels. Firstly, morphological observation of seeds from 13 plus trees showed no significant correlation between polyembryony rate and external environment or seed morphology. Subsequently, comparative transcriptomic analysis between monoembryonic and polyembryonic seeds identified 1957 differentially expressed genes (DEGs), which were significantly enriched in biological processes and pathways including photosystem II, tetrapyrrole binding, heme binding, and phenylpropanoid biosynthesis, indicating the probable effect of gene regulation in polyembryony formation. Furthermore, eight RWP transcription factors were identified, potentially involved in polyembryony. qRT-PCR analysis revealed that the expression levels of PbRWP2 and PbRWP5 were significantly upregulated in polyembryonic seeds, indicating they may be key regulatory genes during polyembryony formation in P. bournei seeds. This study preliminarily explored the transcriptomic characterization and potential molecular regulatory basis of polyembryony formation in P. bournei, laying a critical foundation for further deciphering the intricate mechanisms governing its polyembryonic development. Full article
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16 pages, 6647 KB  
Article
Zfp36l1 Inhibits DNA Damage by Regulating p21-E2F1-Rad51 Signaling During Myogenic Differentiation
by Yi Liu, Xiaoyu Jiang, Jingxin Sun, Luyao Wang, Jialong Li, Honglin Liu, Aiwen Jiang, Shenglong Wu and Wenbin Bao
Int. J. Mol. Sci. 2026, 27(12), 5319; https://doi.org/10.3390/ijms27125319 - 12 Jun 2026
Abstract
Skeletal muscle differentiation relies on transient DNA strand breaks (DSBs), yet excessive DNA damage remains harmful to myogenic progression. The RNA-binding protein Zfp36l1 is expressed in skeletal muscle and contributes to muscle regeneration; nevertheless, its role in preserving genome stability during myogenic differentiation [...] Read more.
Skeletal muscle differentiation relies on transient DNA strand breaks (DSBs), yet excessive DNA damage remains harmful to myogenic progression. The RNA-binding protein Zfp36l1 is expressed in skeletal muscle and contributes to muscle regeneration; nevertheless, its role in preserving genome stability during myogenic differentiation has not been defined. Here, we investigated the role and mechanism of Zfp36l1 in regulating DNA damage using C2C12 myoblast cells, combining loss- and gain-of-function assays, RNA-seq, and rescue experiments. The results revealed that Zfp36l1 expression is strongly induced during early myogenic differentiation, coinciding with the onset of physiological DSBs. Functional assays revealed that silencing Zfp36l1 aggravates DSB accumulation, reinforces G0/G1 cell cycle arrest, and promotes apoptosis, whereas Zfp36l1 overexpression attenuates these abnormalities. Transcriptomic profiling shows that Zfp36l1 depletion impairs homologous recombination (HR)-mediated DNA repair by downregulating core repair factors, including Rad51 and Brca1. Gene set enrichment analysis further confirms significant suppression of the HR-dependent DSB repair pathway. Mechanistically, Zfp36l1 regulates HR repair by suppressing p21 expression, thereby relieving inhibition of E2F1-mediated Rad51 transcription. Co-silencing p21 restores Rad51 expression and reduces DNA damage in Zfp36l1-knockdown cells. Collectively, these findings identify Zfp36l1 as an essential safeguard of genome stability during myogenic differentiation by balancing DNA damage levels through the p21-E2F1-Rad51 signaling axis, and provide new insights into the regulatory basis of muscle development and genomic instability-associated muscle diseases. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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Article
Simulation-Based Multi-Dimensional Evaluation of Ethanol as an Alternative Fuel for Marine Energy Systems
by Hassan M. Attar and Ahmed G. Elkafas
Algorithms 2026, 19(6), 477; https://doi.org/10.3390/a19060477 - 12 Jun 2026
Abstract
The maritime sector accounts for approximately 3% of global greenhouse gas (GHG) emissions and faces binding decarbonization obligations under the International Maritime Organization’s (IMO) Net-Zero Framework and the FuelEU Maritime Regulation. Conventional marine fuels, including very low sulphur fuel oil (VLSFO) and liquefied [...] Read more.
The maritime sector accounts for approximately 3% of global greenhouse gas (GHG) emissions and faces binding decarbonization obligations under the International Maritime Organization’s (IMO) Net-Zero Framework and the FuelEU Maritime Regulation. Conventional marine fuels, including very low sulphur fuel oil (VLSFO) and liquefied natural gas (LNG), are insufficient to meet long-term regulatory intensity targets on a well-to-wake (WtW) lifecycle basis, creating an urgent need for credible fuel alternatives. This study investigates ethanol as a primary fuel for marine dual-fuel propulsion systems, assessed across four distinct production pathways, sugar beet, corn, sugarcane, and wheat straw, to determine its full decarbonization potential relative to VLSFO and LNG benchmarks. A simulation-based multi-dimensional evaluation framework is developed and applied, integrating dynamic operational simulation, energy analysis, environmental lifecycle modelling, and regulatory compliance assessment. The framework is calibrated against a high-resolution dataset from an active container ship, with scenario-specific engine data. While ethanol requires 39.1% more fuel mass than VLSFO due to its lower energy density, all four ethanol pathways deliver substantially superior WtW GHG reductions: from 50.2% (corn) to 76.9% (wheat straw), compared with 20.6% for LNG. All ethanol scenarios satisfy FuelEU compliance limits across the 2026–2045 horizon, with wheat straw ethanol achieving a GFI of 22.52 gCO2e/MJ, compliant marginally with the 2040 IMO target. These findings demonstrate that bio-based ethanol, particularly from lignocellulosic feedstocks, is a technically viable and regulatorily superior alternative to LNG for maritime decarbonization, warranting accelerated research into production scale-up and bunkering infrastructure development. Full article
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