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22 pages, 1872 KB  
Review
Potential Role of Contact Pathway Factors in Catheter-Related Thrombosis: Emerging Evidence and Therapeutic Strategies
by Mingyan Jin, Chunliang Liu, Song Lyu, Aoxue Li, Kesheng Dai and Jun Wan
Biomolecules 2026, 16(9), 1256; https://doi.org/10.3390/biom16091256 (registering DOI) - 29 Aug 2026
Abstract
The catheter is among the most commonly used blood-contacting medical devices, but its use can induce surface-mediated coagulation activation, leading to catheter-related thrombosis (CRT). The occurrence of CRT causes venous thromboembolism and catheter malfunction, but current antithrombotic strategies have unsatisfactory efficacy and safety [...] Read more.
The catheter is among the most commonly used blood-contacting medical devices, but its use can induce surface-mediated coagulation activation, leading to catheter-related thrombosis (CRT). The occurrence of CRT causes venous thromboembolism and catheter malfunction, but current antithrombotic strategies have unsatisfactory efficacy and safety profiles. Here, we review recent advances in the understanding of the pathology of CRT, particularly the roles of the contact pathway factors, and promising novel therapeutic options. Recent studies using genetically modified animals, factor-deficient plasmas, specific inhibitors and purified systems demonstrated an important contribution of contact pathway factors XII and XI to catheter-related blood clotting. Accordingly, contact pathway inhibition has efficacy comparable to that of heparins in mitigating catheter-related coagulation or intraluminal occlusion in various in vitro and animal models, while having lower bleeding risk. Early human studies suggest potential thromboprotective effects of FXI inhibition in catheter placement and hemodialysis settings. However, inhibition of factors XII or XI may impair the defense against infection or disturb normal cardiac function, respectively. Larger human trials are needed to further confirm the efficacy and safety of these contact pathway inhibitors, and to explore whether low-dose combinations of contact pathway inhibitors with heparins are more effective for CRT protection. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms in Anti-Thrombosis)
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30 pages, 9522 KB  
Article
Peripheral Nerve Injury Induces an Interferon-Responsive State Centered on Satellite Glial Cells in the DRG That Sustains Neuropathic Pain Through STAT1 and CXCL10 Signaling
by Wenchao Hu, Futai Wang, Ziyi Niu, Peiyang Liu, Zhicheng Tian, Ceng Luo and Rougang Xie
Brain Sci. 2026, 16(9), 921; https://doi.org/10.3390/brainsci16090921 (registering DOI) - 29 Aug 2026
Abstract
Background: Peripheral nerve injury drives persistent remodeling of the dorsal root ganglion (DRG) microenvironment, but the cellular states and intercellular signaling mechanisms that sustain neuropathic pain remain poorly understood. Methods: Here, we integrated single-cell transcriptomics with histological, behavioral, and electrophysiological approaches to identify [...] Read more.
Background: Peripheral nerve injury drives persistent remodeling of the dorsal root ganglion (DRG) microenvironment, but the cellular states and intercellular signaling mechanisms that sustain neuropathic pain remain poorly understood. Methods: Here, we integrated single-cell transcriptomics with histological, behavioral, and electrophysiological approaches to identify an interferon-responsive state in satellite glial cells (SGCs) of the DRG following spared nerve injury (SNI). Results: This state was distinguished by STAT1-associated interferon-responsive genes’ activation and enhanced chemokine signaling, particularly involving CXCL10 and its receptor CXCR3. These molecular alterations were accompanied by remodeling of intercellular communication among SGCs, sensory neurons, and immune cells. Pharmacological inhibition of STAT1 or blockade of CXCR3 not only reduced sensory-neuron hyperexcitability but also attenuated pain hypersensitivity and improved deficits in hindlimb weight bearing and gait after SNI. Conclusions: Collectively, our findings indicate that interferon-responsive SGCs (IFN SGCs) contribute to the maintenance of neuropathic pain by regulating STAT1-dependent chemokine signaling in the DRG. Targeting this signaling pathway may provide a therapeutic strategy for persistent neuropathic pain. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
38 pages, 1532 KB  
Review
Liposomal Delivery of Hepatoprotective Phytochemicals for Liver Diseases: Advances in Formulation, Targeted Delivery, and Clinical Translation
by Dignesh Khunt, Jigna Khasiya, Sanjay Chauhan, Bhupendra G. Prajapati, Udaykumar Vegad and Sagar Salave
Biomedicines 2026, 14(9), 1946; https://doi.org/10.3390/biomedicines14091946 (registering DOI) - 29 Aug 2026
Abstract
Background/Objectives: Chronic liver diseases (CLDs), including viral hepatitis, alcohol-related liver disease, non-alcoholic fatty liver disease, hepatic fibrosis, and hepatocellular carcinoma, account for approximately two million deaths annually and remain a global health challenge. Although phytochemicals exhibit antioxidant, anti-inflammatory, antifibrotic, and metabolic regulatory activities [...] Read more.
Background/Objectives: Chronic liver diseases (CLDs), including viral hepatitis, alcohol-related liver disease, non-alcoholic fatty liver disease, hepatic fibrosis, and hepatocellular carcinoma, account for approximately two million deaths annually and remain a global health challenge. Although phytochemicals exhibit antioxidant, anti-inflammatory, antifibrotic, and metabolic regulatory activities through modulation of Nrf2/Keap1, NF-κB/MAPK, TGF-β/Smad, and lipid metabolism pathways, their therapeutic translation is hindered by poor aqueous solubility, extensive first-pass metabolism, and low oral bioavailability. This review evaluates the potential of liposomal delivery systems to overcome these limitations and improve hepatic drug targeting. Methods: A structured narrative review was conducted using systematic literature search principles. PubMed/MEDLINE, Scopus, and Web of Science databases were searched for studies published between January 2000 and March 2025. Original research articles evaluating liposomal formulations of hepatoprotective phytochemicals were assessed with emphasis on formulation strategies, pharmacokinetics, therapeutic efficacy, targeting approaches, and translational potential. Results: Liposomal encapsulation frequently improved systemic exposure and, in several preclinical studies, increased oral bioavailability relative to free phytochemicals, although the magnitude of improvement varied substantially according to the compound, formulation, route of administration, and experimental model. Liposomal encapsulation also improved formulation stability and enabled controlled release in several studies. Surface engineering using polyethylene glycol and receptor-specific ligands, including galactose, lactobionic acid, glycyrrhetinic acid, and vitamin A, further improved circulation time and cell-specific hepatic delivery. Emerging technologies such as microfluidic manufacturing, biomimetic liposomes, and multifunctional formulations show promise for improving formulation reproducibility and therapeutic performance, although clinical evidence remains limited. Conclusions: Liposomal delivery represents a promising strategy for enhancing the pharmacokinetic performance and therapeutic efficacy of hepatoprotective phytochemicals. However, additional well-designed clinical studies, scalable manufacturing approaches, and regulatory standardization are required to facilitate successful clinical translation. Full article
(This article belongs to the Special Issue Advanced Research in Liver Diseases)
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19 pages, 1545 KB  
Article
Transcriptomic and Physio-Biochemical Responses of the Fifth-Instar Larvae of Chilo sacchariphagus to High-Temperature Stress
by Ji-Li Wei, Feng-Ying Wang, Yong-Lin Ma, Xian-Kun Shang, Xue-Hong Pan, Ren-Zhao Liao, Liu-Feng Li and Qiao-Xian Wei
Insects 2026, 17(9), 907; https://doi.org/10.3390/insects17090907 (registering DOI) - 29 Aug 2026
Abstract
Chilo sacchariphagus is a destructive sugarcane borer worldwide, and frequent extreme high temperatures disrupt its field populations. Clarifying larval thermal response mechanisms provides theoretical support for pest risk prediction under climate warming. Previous work has illustrated moderate heat induces canonical HSP activation, but [...] Read more.
Chilo sacchariphagus is a destructive sugarcane borer worldwide, and frequent extreme high temperatures disrupt its field populations. Clarifying larval thermal response mechanisms provides theoretical support for pest risk prediction under climate warming. Previous work has illustrated moderate heat induces canonical HSP activation, but the molecular responses of this pest to 41 °C extreme heat remain unclear. As such, we conducted non-reference transcriptome sequencing and 11 physio-biochemical assays on fifth-instar larvae exposed to 41 °C for 12 h (26 °C as control) to characterize its thermal regulatory network. De novo assembly yielded a comprehensive transcriptome resource, and analysis of differentially expressed genes revealed enrichment in energy metabolism, ER protein processing, MAPK signaling and autophagy pathways. Core HSP70/40 transcripts were significantly down-regulated while HSP80 showed stable transcription, suggesting that 41 °C may exceed the heat-shock protective threshold and potentially trigger heat damage. qRT-PCR validation of seven core stress genes confirmed the RNA-seq trends. Catalase (CAT) activity increased significantly; however, none of the annotated catalase genes showed transcriptional changes, whereas elevated CarE and AchE activities also lacked corresponding transcriptional shifts, implying post-translational or alternative regulatory mechanisms. Our data showed coordinated transcriptional and physiological changes under extreme heat. These findings provide a basis for further investigation into how C. sacchariphagus may respond to extreme heat under climate warming scenarios. Full article
(This article belongs to the Section Insect Molecular Biology and Genomics)
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24 pages, 5337 KB  
Article
Ancient Herb, Modern Metabolomics: Primary and Secondary Metabolite Profiling of Wild Fennel (Foeniculum vulgare Mill.) Accessions Under Drought
by Anja Batel, Nikola Major, Marta Anđelini, Nina Išić, Tvrtko Karlo Kovačević, Dean Ban, Igor Pasković and Smiljana Goreta Ban
Plants 2026, 15(17), 2652; https://doi.org/10.3390/plants15172652 (registering DOI) - 29 Aug 2026
Abstract
Fennel (Foeniculum vulgare Mill.) is an aromatic species of culinary and medicinal value, but the metabolic basis of its drought response and the extent of variation among wild populations remain poorly characterized. We investigated eleven wild fennel accessions from the Mediterranean region [...] Read more.
Fennel (Foeniculum vulgare Mill.) is an aromatic species of culinary and medicinal value, but the metabolic basis of its drought response and the extent of variation among wild populations remain poorly characterized. We investigated eleven wild fennel accessions from the Mediterranean region of Croatia under control and drought conditions, combining morphological measurements with targeted profiling of 78 primary and 55 secondary metabolites. Drought significantly reduced biomass, leaf area, length, and width, while leaf dry matter content increased. Primary metabolism shifted markedly: amino acids accumulated, with asparagine and arginine increasing by over 20-fold, whereas TCA-cycle (tricarboxylic acid cycle) organic acids declined. Pathway analysis identified Alanine, aspartate, and glutamate metabolism as most strongly affected by drought treatment. A decline in the GSH/GSSG ratio indicated oxidative stress under water shortage. Among secondary metabolites, free hydroxycinnamic acids and flavonoid aglycones accumulated while most glycosylated flavonoids declined, and eight compounds showed genotype-dependent responses in drought conditions. These results reveal accession-specific metabolic adjustments to drought and characterize Croatian wild fennel as a genetic resource with distinct phytochemical profiles relevant to future conservation and breeding. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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35 pages, 2974 KB  
Review
Extracellular Vesicle-Mediated Macrophage Polarization in Sepsis-Induced Acute Lung Injury: Molecular Mechanisms and Therapeutic Opportunities
by Yiqian Shen, Yi Tai, Xinzhe Liu, Yang Li, Zihao Zhao, Xuejun Jin and Juan Ma
Cells 2026, 15(17), 1574; https://doi.org/10.3390/cells15171574 (registering DOI) - 29 Aug 2026
Abstract
Sepsis-induced acute lung injury (SI-ALI) is a severe complication of sepsis characterized by dysregulated inflammatory responses and impaired immune homeostasis. Growing evidence indicates that extracellular vesicles (EVs), particularly exosomes, are important mediators of intercellular communication. Despite the heterogeneity of infectious sources underlying sepsis, [...] Read more.
Sepsis-induced acute lung injury (SI-ALI) is a severe complication of sepsis characterized by dysregulated inflammatory responses and impaired immune homeostasis. Growing evidence indicates that extracellular vesicles (EVs), particularly exosomes, are important mediators of intercellular communication. Despite the heterogeneity of infectious sources underlying sepsis, EVs can regulate macrophage polarization and functional reprogramming by transferring diverse bioactive cargo. Consequently, EVs are involved in the pathophysiological progression of SI-ALI arising from sepsis of different etiologies. However, the mechanisms through which distinct EV cargos regulate macrophage function and contribute to SI-ALI pathogenesis remain incompletely understood. To address these issues, this review summarizes how different EV subtypes and their cargos, including RNAs, proteins, lipids, and DNA, modulate macrophage functional states through multiple signaling pathways. The effect of such processes further contributes to inflammatory reaction, immune balance, and tissue regeneration in acute lung injury caused by damage to the SI-ALI. Particularly, the EV-mediated modulation of macrophage function goes beyond the rigid M1/M2 dichotomy, being rather based on the dynamic functional repertoire involving both pro-inflammatory response and immune regulation as well as tissue regeneration. The article finally concludes with EV-based treatment approaches aimed at cargo delivery or blocking and the main problems related to translational medicine. Overall, the review article identifies the macrophage regulatory network controlled by EVs, thus helping to understand immunopathogenesis of SI-ALI as well as laying the theoretical foundation for developing EV-based precision medicine. Full article
(This article belongs to the Section Cellular Immunology)
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13 pages, 1116 KB  
Article
Selective Redox Tuning Enables Potent Intracellular Reduction of Nicotinamide Cytosine Dinucleotide
by Xiaojia Guo, Yanzhe Huang, Yinghan Hu, Lingyun Zhang and Zongbao K. Zhao
Biomolecules 2026, 16(9), 1255; https://doi.org/10.3390/biom16091255 (registering DOI) - 29 Aug 2026
Abstract
The ubiquitous nicotinamide adenine dinucleotide (NAD) engages in diverse biological processes, leading to non-selective energy transfer toward target synthetic reactions. To achieve selective energy transfer in complex biological systems, we previously constructed artificial systems mediated by the non-natural cofactor nicotinamide cytosine dinucleotide (NCD), [...] Read more.
The ubiquitous nicotinamide adenine dinucleotide (NAD) engages in diverse biological processes, leading to non-selective energy transfer toward target synthetic reactions. To achieve selective energy transfer in complex biological systems, we previously constructed artificial systems mediated by the non-natural cofactor nicotinamide cytosine dinucleotide (NCD), which can be specifically recognized by engineered enzymes with minimal cross-talk with natural cofactors. For enhanced energy transfer and higher product yields, efficient conversion of NCD to NCDH is required to deliver reducing power in NCD-mediated biosynthetic pathways. Here, we established a comprehensive strategy for selective reduction in intracellular NCD. First, coupled enzymatic colorimetric assays with high specificity were validated for quantifying NAD, NADP, and NCD. With phosphite as the energy source, we selectively elevated the intracellular NCDH/NCD ratio with minimal perturbation to NADH/NAD and NADPH/NADP ratios in E. coli. To overcome the limitation of phosphite transmembrane transport, cell-free systems were constructed to confirm that phosphite could drive near-complete NCD reduction. Finally, cells were treated with polymyxin B, which promoted phosphite uptake and thereby enabled maximal reduction in intracellular NCD. An NCDH/NCD ratio of 47 was achieved, demonstrating that 98% of the intracellular NCD pool existed in the reduced form. This work demonstrates that NCD can function as an independent redox cofactor for selective regulation, providing viable strategies for artificial cofactor-driven biosynthesis. Full article
(This article belongs to the Section Chemical Biology)
40 pages, 35432 KB  
Article
Future Vegetation Dynamics in an Arid Inland River Basin Under CMIP6 Scenarios: Insights from a Machine Learning Framework
by Weixiang Sun, Jiayi Zheng, Linwei Guan, Peilin Lan, Haoran Lu and Abudukeyimu Abulizi
Land 2026, 15(9), 1596; https://doi.org/10.3390/land15091596 (registering DOI) - 29 Aug 2026
Abstract
Against the backdrop of global warming and the “warming and moistening” trend in northwestern China, arid inland river basins are highly sensitive to climate change, with their vegetation dynamics strongly controlled by upstream snowmelt water supply. The Keriya River Basin, situated on the [...] Read more.
Against the backdrop of global warming and the “warming and moistening” trend in northwestern China, arid inland river basins are highly sensitive to climate change, with their vegetation dynamics strongly controlled by upstream snowmelt water supply. The Keriya River Basin, situated on the northern slope of the Kunlun Mountains and the southern edge of the Taklamakan Desert, exhibits pronounced vertical zonation in vegetation cover and relies heavily on upstream snowmelt water supply for its water resources. To date, there has been a lack of systematic research into the spatiotemporal evolution patterns of long-term NDVI time series in this basin, its multiscale climate responses, and, in particular, future vegetation projections based on CMIP6 multi-scenario analyses and machine learning methods. To address this, this study utilised MODIS NDVI remote sensing data, historical data from the CMIP6 BCC-CSM2-MR model, and monthly temperature, precipitation, and snow cover data for three SSP scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5) and systematically analysed the spatiotemporal differentiation characteristics of NDVI in the Keriya River Basin and its multiscale coupling relationships with climatic factors. A multi-model selection and forecasting framework was developed, integrating feature engineering with the XGBoost machine learning algorithm. The study innovatively introduced a physically constrained scenario scaling factor based on historical correlations and future climate mean values, thereby addressing the bias where machine learning models’ predicted NDVI means converged across different SSP scenarios. This enabled the monthly estimation of NDVI under various emission pathways from 2015 to 2100. The results indicate: (1) During the historical period (2001–2024), the basin’s annual average NDVI showed an overall slight increase; the annual pattern was unimodal, peaking in July and reaching its trough in January–February; NDVI was highest in summer and lowest in winter. (2) NDVI initially increases and then decreases with altitude; the highest NDVI values are observed in the 3000–4000 m altitude band; in the mid-altitude band, NDVI rose significantly after 2010 and peaked in 2017; the low-altitude band exhibits the greatest interannual stability. (3) During the historical period, both temperature and precipitation in the catchment exhibited high levels of fluctuation, with annual mean temperatures ranging from 1.90 to 3.92 °C and annual precipitation ranging from 434.5 to 621.0 mm. NDVI showed a strong positive correlation with temperature (R = 0.86), a relatively strong negative correlation with snow cover (R = −0.71), and virtually no correlation with precipitation, indicating that upstream snowmelt is heat-driven and water-dependent. (4) Under the future SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios, temperature increases are projected to be 0.83 °C, 2.68 °C, and 5.35 °C, respectively, whilst snow cover is projected to decrease by 2.0%, 14.3%, and 34.0%, respectively; The multi-year mean NDVI values predicted using the XGBoost model (validation R2 = 0.9097) are 0.0726, 0.0683, and 0.0690, respectively, all characterised by strong seasonal fluctuations. Given that these future projections are based on a single CMIP6 model and a statistical forecasting framework, they are subject to a degree of uncertainty; however, the low-emission scenario (SSP1-2.6) still indicates a trend that is relatively more conducive to maintaining vegetation stability in this region and may provide preliminary scientific guidance for water resource management along the southern margin of the Tarim Basin. Full article
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14 pages, 2821 KB  
Article
Comparative Diagnostic Performance of IOTA Simple Rules, the ADNEX Model, and ACR O-RADS in a Selected Surgical Cohort of Adnexal Masses: A Retrospective Study
by Lijun Wu, Yun Wu, Tao Hu, Juan Qian, Zhaoli Fan and Pingyang Zhang
J. Clin. Med. 2026, 15(17), 6717; https://doi.org/10.3390/jcm15176717 (registering DOI) - 29 Aug 2026
Abstract
Background/Objectives: The accurate preoperative risk stratification of adnexal masses is clinically important. This study compared the diagnostic performance of the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model, and the American College [...] Read more.
Background/Objectives: The accurate preoperative risk stratification of adnexal masses is clinically important. This study compared the diagnostic performance of the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model, and the American College of Radiology Ovarian-Adnexal Reporting and Data System (ACR O-RADS). Methods: This retrospective comparative study analyzed 429 women from a selected surgical dataset with pathology restrictions at a tertiary hospital in Nanjing, China, between January 2022 and October 2024. Two experienced gynecologic ultrasonographers independently applied SR, ADNEX (test-positive at a malignancy risk ≥ 10%), and O-RADS (test-positive at categories 4–5). Surgical histopathology served as the reference standard. Diagnostic performance was evaluated using exact binomial 95% confidence intervals (CIs), paired comparisons, receiver operating characteristic (ROC) analysis, ADNEX calibration, observed malignancy proportions across O-RADS categories, and interobserver agreement. Results: Among the 429 selected index adnexal masses, 114 (26.6%) were malignant. SR produced inconclusive classifications for 81 masses (18.9%). When SR-malignant and SR-inconclusive classifications were both regarded as positive indications for referral, SR achieved a sensitivity of 83.3% (95% CI, 75.2–89.7%) and a specificity of 84.1% (95% CI, 79.6–88.0%). ADNEX achieved a sensitivity of 86.0% (95% CI, 78.2–91.8%) and a specificity of 81.9% (95% CI, 77.2–86.0%), whereas O-RADS achieved a sensitivity of 89.5% (95% CI, 82.3–94.4%) and a specificity of 83.5% (95% CI, 78.9–87.4%). The AUCs for ADNEX and O-RADS were 0.92 and 0.90, respectively, with no statistically significant difference identified by paired DeLong analysis (p = 0.16). After Holm adjustment, none of the pairwise comparisons of sensitivity or specificity reached statistical significance. ADNEX exhibited apparent overall underprediction (calibration intercept, 0.865; calibration slope, 1.022; Brier score, 0.096). For O-RADS categories 2 and 4, the point estimates of observed malignancy proportions fell outside the corresponding predefined risk ranges. Interobserver agreement was almost perfect for O-RADS (κ = 0.89) and substantial for ADNEX (κ = 0.79) and SR (κ = 0.68). Conclusions: Within this selected surgical dataset subject to pathology-based restrictions, SR, ADNEX, and O-RADS demonstrated distinct diagnostic performance profiles. Following Holm adjustment, no statistically significant differences in sensitivity or specificity were detected among the three systems. Analyses of masses receiving an inconclusive SR classification were exploratory and therefore do not establish the validity of a sequential diagnostic pathway. Prospective multicenter investigations involving unselected populations are warranted before these findings can be generalized to broader clinical populations. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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18 pages, 4453 KB  
Article
Effects of Fixation and Drying on the Physicochemical Quality and Aroma Profiles of Vine Tea (Nekemias grossedentata): Identification of Critical Processing Steps for Flavor Formation
by Fei Ye, Kui Chen, Anhui Gui, Yayan Yu, Chaoyang Zhang, Panpan Liu, Xueping Wang, Lin Feng, Jin Teng, Jinjin Xue, Pengcheng Zheng and Shiwei Gao
Foods 2026, 15(17), 3067; https://doi.org/10.3390/foods15173067 (registering DOI) - 29 Aug 2026
Abstract
The quality and flavor of vine tea are largely determined by its processing stages, which markedly influence its physical attributes and volatile organic compounds. Elucidating the dynamic changes in physicochemical and aromatic properties throughout processing is, therefore, essential for guiding optimized processing techniques [...] Read more.
The quality and flavor of vine tea are largely determined by its processing stages, which markedly influence its physical attributes and volatile organic compounds. Elucidating the dynamic changes in physicochemical and aromatic properties throughout processing is, therefore, essential for guiding optimized processing techniques and developing high-quality vine tea products. However, the specific effects of individual processing stages on quality attributes remain poorly understood. In this study, we combined assessments of color and physical properties with untargeted metabolomics, headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC-MS), relative odor activity value (ROAV), and gas chromatography–olfactometry (GC-O) to identify key compounds contributing to vine tea quality. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were further applied to identify characteristic metabolites associated with aroma and flavor differentiation. A total of 280 volatile organic compounds were identified, among which 14 key VOCs (ROAV ≥ 1, aroma intensity ≥ 0.5) exhibited significant dynamic variation across processing stages. Notably, compounds such as β-ionone, β-myrcene, nonanal, and hexanal displayed higher ROAVs and strong aroma intensities (AI ≥ 1.0), indicating their substantial contribution to overall aroma. Furthermore, the metabolic transformation pathways—primarily including fatty acid degradation and carotenoid cleavage—and the content changes of key aroma-active compounds were inferred across different processing stages. Based on the differential accumulation patterns of the identified volatile markers, the possible involvement of fatty acid degradation and carotenoid cleavage pathways was inferred. Drying and fixation emerged as critical steps for vine tea aroma development, while the non-enzymatic degradation of fatty acids was potentially associated with the formation of its aroma characteristics. This study provides insights that may inform future efforts toward processing optimization and quality improvement of vine tea. Full article
(This article belongs to the Special Issue Advanced Food Processing Technologies and Approaches: 2nd Edition)
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22 pages, 2540 KB  
Article
Transcriptional Heterogeneity Underlying Cancer Cell Migration Converges on Shared Regulatory Programs
by Ismael Ortiz, Paul V. Taufalele, Victor L. Dunagan, Samantha S. Hodge, Jing Wang, Qi Liu and Cynthia A. Reinhart-King
Genes 2026, 17(9), 1042; https://doi.org/10.3390/genes17091042 (registering DOI) - 29 Aug 2026
Abstract
Background/Objectives: Cancer cell migration is a hallmark of cancer and is associated with metastasis. While large-scale functional screens have identified regulators of migration, less is known about how intrinsic transcriptional heterogeneity drives highly migratory phenotypes within individual cancer models or whether these [...] Read more.
Background/Objectives: Cancer cell migration is a hallmark of cancer and is associated with metastasis. While large-scale functional screens have identified regulators of migration, less is known about how intrinsic transcriptional heterogeneity drives highly migratory phenotypes within individual cancer models or whether these transcriptional changes are conserved across different models of varying tissues of origin. This study aims to define shared and cell line-specific transcriptional programs associated with cancer cell migration and analyze their relevance to patient datasets. Methods: Five cancer cell lines across three cancer types (breast, colorectal, and melanoma) were subjected to transwell-based migratory sorting to isolate highly and weakly migratory subpopulations. Bulk RNA sequencing, differential gene expression analysis, Gene Ontology (GO) enrichment, and upstream regulator prediction were performed. Public tumor datasets were analyzed to evaluate gene expression and its association with patient survival. Results: EVA1A was consistently upregulated in all highly migratory (HM) subpopulations. Multiple GO terms were enriched across all cell lines, often driven by distinct gene signatures, indicating convergence at the level of biological processes despite transcriptional divergence. TEAD4 was predicted as an upstream regulator, and increased TEAD4 nuclear localization was observed in four of the five HM subpopulations. EVA1A and TEAD4 expression were elevated in tumors relative to normal tissues, with cancer type-dependent survival outcomes. Conclusions: Migratory selection was accompanied by extensive transcriptional change within each model, yet across five models spanning three tissue types these changes converged on shared biological processes rather than shared genes. Migration-associated phenotypes may therefore be better defined by pathway-level than single-gene analyses, and the clinical relevance of regulatory nodes such as TEAD4 appears conditional on cancer type. Full article
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32 pages, 1190 KB  
Review
Iron Deficiency in Endocrine Diseases and the Therapeutic Role of Liposomal Iron: A Comprehensive Review
by Sandro La Vignera and Rosita A. Condorelli
Biomedicines 2026, 14(9), 1944; https://doi.org/10.3390/biomedicines14091944 (registering DOI) - 29 Aug 2026
Abstract
Iron deficiency (ID) represents one of the most prevalent nutritional disorders worldwide, affecting approximately 1.2 billion individuals. Beyond its well-established hematological consequences, emerging evidence demonstrates that ID profoundly impacts endocrine function across multiple organ systems. Iron serves as an essential cofactor for numerous [...] Read more.
Iron deficiency (ID) represents one of the most prevalent nutritional disorders worldwide, affecting approximately 1.2 billion individuals. Beyond its well-established hematological consequences, emerging evidence demonstrates that ID profoundly impacts endocrine function across multiple organ systems. Iron serves as an essential cofactor for numerous enzymes involved in hormone synthesis, metabolism, and signaling pathways. This comprehensive review examines the bidirectional relationships between iron deficiency and endocrine pathologies, including thyroid disorders (hypothyroidism, Hashimoto’s thyroiditis, thyroid peroxidase impairment), diabetes mellitus (types 1 and 2), obesity, Polyendocrine Metabolic Ovarian Syndrome (PMOS), male hypogonadism, adrenal insufficiency, growth hormone deficiency, pituitary dysfunction, and parathyroid disorders. We systematically analyze the molecular mechanisms linking iron metabolism to endocrine dysfunction, with particular emphasis on thyroid peroxidase activity, insulin secretion and sensitivity, hepcidin regulation, testosterone synthesis, and cortisol production. Furthermore, we critically evaluate the therapeutic potential of liposomal iron supplementation, a novel delivery system that offers superior bioavailability and gastrointestinal tolerability compared to conventional oral iron formulations. Randomized controlled trials demonstrate that liposomal iron achieves comparable efficacy to intravenous iron while significantly reducing adverse events. This review synthesizes current evidence to provide clinicians with a comprehensive understanding of iron-endocrine interactions and evidence-based recommendations for iron supplementation in endocrine disorders. Recognition of these complex relationships is essential for optimizing diagnostic and therapeutic approaches in patients with concurrent iron deficiency and endocrine dysfunction. Full article
(This article belongs to the Special Issue The Role of Iron in Human Diseases)
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30 pages, 679 KB  
Review
Dietary Nitrate Bioactivation at the Diet–Microbiota–Host Interface: The Enterosalivary Cycle, Food Matrix, Microbial Determinants and Health Implications—A Narrative Review Supported by a Structured Literature Search
by Gilda-Diana Buzatu, Ana-Maria Dodocioiu, Eleonora Daniela Ciupeanu-Călugaru, Dumitru Radulescu and Emil-Tiberius Trască
Nutrients 2026, 18(17), 2841; https://doi.org/10.3390/nu18172841 (registering DOI) - 29 Aug 2026
Abstract
Background/Objectives: Dietary nitrate, long framed through food-safety concerns about N-nitroso compound formation, is now also recognised as a substrate of the nitrate–nitrite–nitric oxide pathway. This review aims to define the mechanistic, dietary and host conditions under which nitrate bioactivation becomes functionally relevant, with [...] Read more.
Background/Objectives: Dietary nitrate, long framed through food-safety concerns about N-nitroso compound formation, is now also recognised as a substrate of the nitrate–nitrite–nitric oxide pathway. This review aims to define the mechanistic, dietary and host conditions under which nitrate bioactivation becomes functionally relevant, with particular attention to its microbial determinants and to the level of inference the evidence actually supports. Methods: We conducted a narrative review supported by a structured literature search (PubMed, Scopus and Web of Science; 1 January 1976 to 14 February 2026; full-text, peer-reviewed, English-language, human-relevant sources; 148 sources retained, of which 93 contributed to the evidence synthesis), with narrative synthesis of mechanistic, interventional, observational and regulatory sources addressing dietary source and food matrix, enterosalivary metabolism, oral and gut microbial function, and health-related outcomes. A PRISMA-style flow diagram summarises the documented screening and inclusion process, and the complete database-specific search strategies are provided in Supplementary Table S1; no meta-analysis was performed because of substantial heterogeneity in designs and outcomes. Results: Within the canonical enterosalivary pathway, nitrate-to-nitrite bioactivation is predominantly microbiota-dependent and downstream conversion is chemically conditional: within the enterosalivary cycle, nitrate-reducing bacteria on the tongue dorsum generate the nitrite required for downstream nitric oxide formation, and its conversion in the stomach depends on pH and on matrix constituents. Dietary source and food matrix therefore govern both the delivered dose and the chemistry that follows, so vegetables, beetroot products, inorganic salts, drinking water and processed meat are not interchangeable exposure models. The oral microbiota is the principal microbial determinant of the response, whereas the gut microbiota acts as a context-dependent modifier of intestinal redox tone, barrier function and microbial ecology, supported by markedly weaker human evidence. Nitrate-rich sources reproducibly raise nitrate and nitrite biomarkers, with variable effects on blood pressure, vascular function and exercise efficiency, limited or inconsistent effects on cognition, cerebral blood flow and metabolic endpoints, and a safety profile whose interpretation depends on food matrix, dose, exposure pattern and host context rather than concentration alone. Conclusions: We propose the Source–Matrix–Microbiota–Host (SMMH) framework, in which biological impact depends on the interaction between dietary source and dose, food matrix, microbial nitrate-reducing capacity and host susceptibility, rather than on nitrate dose alone, and in which pathway-level, physiological and clinical evidence are kept explicitly distinct. The evidence base is mechanistically robust for the oral microbiota, considerably less defined for the gut microbiota, and variable at the level of validated clinical endpoints; it does not yet support source-independent guidelines or population-level recommendations. Full article
(This article belongs to the Special Issue Exploring the Lifespan Dynamics of Oral–Gut Microbiota Interactions)
19 pages, 4595 KB  
Article
Transcriptomic and Zonal Signatures of Mitochondrial Peroxisomal Dysfunction in HCV Associates with Circulating Mitochondrial DNA Biomarkers
by Moumita Chakraborty, Rownock Afruza, Maleeha F. Ahmad, Matthew G. Menkart, Jenna L. Oringher, Adekanyinsola Onitiri, Nicole Minerva, Kareen Akiva, Grace Zhang, Elizabeth C. Townsend, Gabriella Quinn, Anjali Rai, David E. Kleiner, Elliot Levy, Christopher Koh, Ohad Etzion, Rabab O. Ali and Theo Heller
Curr. Issues Mol. Biol. 2026, 48(9), 877; https://doi.org/10.3390/cimb48090877 (registering DOI) - 29 Aug 2026
Abstract
Mitochondria and peroxisomes are critical for hepatic energy metabolism, lipid homeostasis, and reactive oxygen species (ROS) detoxification. In chronic hepatitis C virus (HCV) infection, continuous injury leads to cirrhosis; however, the spatial arrangement and reversibility of organelle dysfunction remain poorly understood. This study [...] Read more.
Mitochondria and peroxisomes are critical for hepatic energy metabolism, lipid homeostasis, and reactive oxygen species (ROS) detoxification. In chronic hepatitis C virus (HCV) infection, continuous injury leads to cirrhosis; however, the spatial arrangement and reversibility of organelle dysfunction remain poorly understood. This study aimed to examine the zonal distribution of mitochondrial and peroxisomal injury in liver biopsies and elucidate the role of circulating cell-free mitochondrial DNA (ccfDNA) in patients with chronic HCV and cirrhosis following antiviral therapy. We employed advanced microscopy imaging and transcriptomic analysis of liver biopsies and quantified ccf-mtDNA as a noninvasive marker of mitochondrial injury in the peripheral blood of these patients. Transcriptomic data revealed alterations in mitochondrial and peroxisomal pathway alterations in HCV-infected patients. The imaging data displayed distinct zone-specific patterns of organelle damage. Following viral removal, significant improvement in mitochondrial and peroxisomal protein expression were noted, indicating partial recovery of organelle integrity following viral clearance; whether this reflects true subcellular regeneration or an early stage of a longer recovery process remains to be determined. Additionally, we showed that ccf-mtDNA quantitatively reflects intrahepatic mitochondrial dysfunction, indicating its potential as a diagnostic biomarker in therapeutic approaches. These findings indicate that organelle injury in chronic HCV is spatially patterned, disease severity-dependent, and partially reversible following antiviral therapy. Full article
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24 pages, 2624 KB  
Review
Advances in Fluorescent Inorganic–Organic Hybrid Nanostructures: Interfacial and Photophysical Insights for Selective Pesticide Sensing and Removal
by Roberto Acevedo, Harbinder Singh, Mikhael Bechelany, Rajat Bajaj and Jagpreet Singh
Nanomaterials 2026, 16(17), 1076; https://doi.org/10.3390/nano16171076 (registering DOI) - 29 Aug 2026
Abstract
The extensive use of pesticides in modern agriculture has resulted in their persistent accumulation in environmental systems, posing significant risks to ecosystems and human health. Consequently, the development of integrated strategies for the sensitive detection and efficient removal of pesticide residues has become [...] Read more.
The extensive use of pesticides in modern agriculture has resulted in their persistent accumulation in environmental systems, posing significant risks to ecosystems and human health. Consequently, the development of integrated strategies for the sensitive detection and efficient removal of pesticide residues has become critically important. In this context, fluorescent inorganic–organic hybrid nanoparticles have emerged as versatile platforms owing to their tunable physicochemical properties and distinctive optical behavior. This review provides a comprehensive overview of recent advances in these hybrid nanomaterials for pesticide sensing and remediation. Particular emphasis is placed on the underlying photophysical mechanisms governing detection, including fluorescence quenching, Förster resonance energy transfer (FRET), inner filter effect (IFE), and photoinduced electron transfer (PET). In parallel, the role of interfacial interactions such as hydrogen bonding, electrostatic attraction, and π–π stacking in adsorption processes is critically discussed. Furthermore, these hybrid systems exhibit high adsorption capacities and rapid removal kinetics, enabling efficient pesticide elimination using both adsorption and catalytic degradation pathways. Overall, this review underscores the potential of fluorescent inorganic–organic hybrid nanoparticles as next-generation materials for sustainable environmental monitoring and remediation of pesticide contaminants. Full article
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