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18 pages, 16508 KB  
Article
Influence of PLA Flowability and Talc Content on the Performance of Rigid TPS/PBS/PLA/Talc Blends
by Cristina Martín-Poyo, Josep P. Cerisuelo and Jose D. Badia-Valiente
Polymers 2026, 18(12), 1544; https://doi.org/10.3390/polym18121544 (registering DOI) - 21 Jun 2026
Abstract
This study investigates the influence of PLA flowability and talc content on the performance of compostable thermoplastic starch/poly(butylene succinate) (TPS/PBS)-based systems for rigid applications. Different PLA grades with varying melt flow index (PLA23, PLA8 and PLA70) and talc contents (0, 5 and 10 [...] Read more.
This study investigates the influence of PLA flowability and talc content on the performance of compostable thermoplastic starch/poly(butylene succinate) (TPS/PBS)-based systems for rigid applications. Different PLA grades with varying melt flow index (PLA23, PLA8 and PLA70) and talc contents (0, 5 and 10 wt%) were incorporated. Twelve formulations were compounded by twin-screw extrusion and processed by injection moulding. FTIR confirmed the coexistence of TPS, PBS and PLA phases without evidence of chemical interactions. Morphological analysis showed that PLA flowability plays a key role in phase distribution, with higher-flow PLA promoting improved dispersion and interfacial adhesion, while talc addition (5 and 10 wt%) increased structural heterogeneity; at higher loadings, particularly, DSC analysis revealed that talc acted as a nucleating agent for the PBS phase, increasing crystallisation temperatures from approximately 73 °C to 81 °C depending on formulation. Mechanical results showed that Young’s modulus increased from approximately 1.4 GPa to 2.7 GPa with decreasing PLA flowability and increasing talc content. Formulations containing low-flow PLA reached tensile strengths close to 32 MPa, although elongation at break decreased to values near 2%. In contrast, high-flow PLA formulations exhibited a more balanced mechanical response, with elongation values up to approximately 8%, associated with improved phase dispersion. Hybrid PLA systems showed intermediate behaviour, reaching elongations up to 22% while maintaining modulus values around 1.8 GPa. Talc provided additional reinforcement but reduced deformation capacity. HDT values remained relatively constant, indicating limited improvement in thermomechanical resistance despite increased stiffness. These results demonstrate that the combined control of PLA molecular characteristics and talc content enables tuning of the mechanical and thermomechanical performance of TPS/PBS/PLA/talc systems for rigid packaging applications. Full article
(This article belongs to the Special Issue Design and Performance of Compostable Polymeric Packaging Materials)
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25 pages, 18288 KB  
Article
Infill Pattern-Dependent Mechanical Properties and In Vitro Release Behavior of FDM 3D-Printed Resveratrol Amorphous Solid Dispersion Matrix Tablets
by Lianghao Huang, Kai Zheng, Xiaofeng Chen, Yunping Zhao, Tiantian Yang, Hang Yu, Wei Zhao, Xia Zhao and Jiaxiang Zhang
Polymers 2026, 18(12), 1531; https://doi.org/10.3390/polym18121531 (registering DOI) - 19 Jun 2026
Viewed by 147
Abstract
Resveratrol (RSV) is a poorly water-soluble polyphenolic compound with various potential health benefits, but its pharmaceutical application is limited by low aqueous solubility and poor oral bioavailability. Additive manufacturing (AM), particularly fused deposition modeling (FDM) 3D printing, offers a flexible approach for fabricating [...] Read more.
Resveratrol (RSV) is a poorly water-soluble polyphenolic compound with various potential health benefits, but its pharmaceutical application is limited by low aqueous solubility and poor oral bioavailability. Additive manufacturing (AM), particularly fused deposition modeling (FDM) 3D printing, offers a flexible approach for fabricating oral dosage forms with customized geometry and internal architecture. In this study, hot-melt extrusion (HME) combined with fused deposition modeling (FDM) 3D printing was used to prepare RSV-loaded tablets with different infill patterns. Hydroxypropyl methylcellulose acetate succinate and hydroxypropyl cellulose were selected as polymeric carriers to prepare RSV-loaded filaments suitable for FDM printing. The effects of infill pattern on the solid-state characteristics, dimensional accuracy, mechanical properties, floating behavior, and in vitro drug release of the printed tablets were systematically investigated. Differential scanning calorimetry, powder X-ray diffraction, and polarized light microscopy indicated that RSV was mainly converted into an amorphous or molecularly dispersed state after HME and FDM processing. All designed tablets were successfully printed and showed acceptable shape fidelity, while different infill patterns resulted in variations in tablet weight, mechanical strength, floating duration, and release behavior. In vitro dissolution studies showed that the RSV release profiles were dependent on the internal infill architecture. Tablets with more complex infill patterns generally exhibited slower drug release, which may be related to differences in internal pore structure, medium penetration pathways, matrix hydration, and diffusion distance. Release kinetic analysis further suggested that RSV release from the printed tablets involved a combination of diffusion and polymer relaxation processes. These results demonstrate that infill pattern is an important structural parameter for modulating the mechanical performance and drug release behavior of FDM 3D-printed RSV tablets. This study provides useful guidance for the design of 3D-printed oral dosage forms with tunable release characteristics. Full article
(This article belongs to the Special Issue Advancements in Polymeric Materials for Precision Drug Delivery)
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12 pages, 1148 KB  
Article
Analytical and Organoleptic Evaluation of Caffeinated Grape Must
by Rita Székelyhidi and Beatrix Sik
AppliedChem 2026, 6(2), 41; https://doi.org/10.3390/appliedchem6020041 - 18 Jun 2026
Viewed by 67
Abstract
This study aimed to produce, analyze, and evaluate the consumer acceptance of caffeine-enriched (15, 30, 60, and 90 mg/100 mL) grape must, which does not contain any added sweeteners or preservatives, to meet today’s popular health-conscious consumer trends. Regarding acid composition, the musts [...] Read more.
This study aimed to produce, analyze, and evaluate the consumer acceptance of caffeine-enriched (15, 30, 60, and 90 mg/100 mL) grape must, which does not contain any added sweeteners or preservatives, to meet today’s popular health-conscious consumer trends. Regarding acid composition, the musts contained malic acid (426.96–491.58 mg/100 mL) and succinic acid (74.53–84.79 mg/100 mL). Musts are regarded as water-soluble sugars, containing only glucose (6158.81–9417.09 mg/100 mL) and fructose (6798.37–10,482.53 mg/100 mL), which are typical in fruits. The must’s TPC and TAC contents were determined to be between 11.42 and 14.14 mg GAE/100 mL, and 8.14 and 11.80 mg AAE/100 mL, respectively. During the analysis of caffeine content, recovery values of 93.89–96.98% were determined. The must samples containing 60 and 90 mg/100 mL caffeine had too intense a bitter flavor; thus, the enjoyment value of the products was reduced based on consumer feedback. The must containing 15 mg/100 mL of caffeine had the most favorable organoleptic properties. Full article
(This article belongs to the Special Issue Analytical Chemistry: Fundamentals, Current and Future Applications)
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17 pages, 6075 KB  
Article
Multi-Omics Integration Uncovers That Tenofovir Disoproxil Fumarate Is Linked to Hepatic Metabolic Reprogramming Independent of Viral Infection
by Yuanqin Duan, Yunling Xue, Jing Tang, Teng Long, Zhiwei Chen, Mingli Peng and Peng Hu
Life 2026, 16(6), 1017; https://doi.org/10.3390/life16061017 - 17 Jun 2026
Viewed by 163
Abstract
Background and Aims: TDF is a first-line antiviral for CHB with pleiotropic effects including immunomodulation and fibrosis regression, but its virus-independent mechanisms are unclear. This study delineates TDF’s direct molecular and metabolic landscape in vivo using multi-omics. Methods: Wild-type mice received TDF or [...] Read more.
Background and Aims: TDF is a first-line antiviral for CHB with pleiotropic effects including immunomodulation and fibrosis regression, but its virus-independent mechanisms are unclear. This study delineates TDF’s direct molecular and metabolic landscape in vivo using multi-omics. Methods: Wild-type mice received TDF or vehicle for 4 months. Liver tissues underwent RNA-seq and targeted metabolomics, followed by integrative systems biology. Results: TDF caused no hepatotoxicity but induced transcriptomic reprogramming: broad upregulation of immune/inflammatory pathways and suppression of metabolic pathways. Metabolomics confirmed perturbations in amino acid and fatty acid homeostasis. Multi-omics revealed coordinated downregulation of arginine/proline, alanine/aspartate/glutamate, and phenylalanine metabolism, restricting fibrogenic amino acids. TDF also suppressed the TCA cycle (downregulating Idh, Sdh, and Mdh), suggesting a metabolic bottleneck that was associated with paradoxically accumulated succinate and oxoglutarate—immunomodulatory danger signals. Conclusions: This first integrated atlas shows TDF actively remodels the hepatic microenvironment independent of viral infection, bridging metabolic suppression with immune activation. These findings provide an immunometabolic framework that offers new perspectives for understanding the clinical application of TDF and identifies potential biomarkers for CHB therapy. explaining TDF’s clinical superiority and identifying potential biomarkers for CHB therapy. Full article
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15 pages, 20762 KB  
Article
Benzovindiflupyr Is Associated with Metabolic Homeostasis Disturbance and Gut–Liver Axis Alterations in Zebrafish: Insights from a Multi-Omics Approach
by Jiyan Miao, Shihang Han, Xinrui Dang, Qi Chen, Jinling Diao and Wentao Zhu
Int. J. Mol. Sci. 2026, 27(12), 5455; https://doi.org/10.3390/ijms27125455 - 17 Jun 2026
Viewed by 107
Abstract
Benzovindiflupyr (BZF) is a newly developed succinate dehydrogenase inhibitor (SDHI) fungicide that is widely used in crop protection, but its potential effects on non-target aquatic organisms remain a concern. In this study, we exposed adult zebrafish (Danio rerio) to 5.0 and [...] Read more.
Benzovindiflupyr (BZF) is a newly developed succinate dehydrogenase inhibitor (SDHI) fungicide that is widely used in crop protection, but its potential effects on non-target aquatic organisms remain a concern. In this study, we exposed adult zebrafish (Danio rerio) to 5.0 and 50 μg/L BZF for 28 days. We investigated its impact on the gut–liver axis using a combination of microbiome, biochemical, histological, and metabolomic analyses. BZF exposure damaged intestinal structure, downregulated barrier-related genes, and altered the composition of the gut microbiota. At the same time, serum lipopolysaccharide (LPS) levels increased, which indicates impaired intestinal barrier integrity and microbial dysbiosis. In the liver, BZF caused histopathological alterations, increased serum ALT, AST, and ALP activities, enhanced oxidative stress, and upregulated inflammation-related genes. Liver metabolomic profiling further showed marked disturbances in redox balance and metabolic homeostasis. Correlation analysis also revealed significant associations between altered microbial taxa and differential liver metabolites. Taken together, these results suggest that BZF exposure disrupted intestinal homeostasis and was associated with hepatic metabolic disturbance in zebrafish, potentially through gut–liver axis perturbation. This study expands current understanding of the toxic effects of SDHI fungicides and provides useful evidence for the ecological risk assessment of BZF in aquatic environments. Full article
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24 pages, 2514 KB  
Review
Oral Barrier Immunometabolism in Chronic Low-Grade Inflammation: Molecular Mechanisms and Systemic Implications
by Aferdita Ademi, Skender Topi, Mitilda Gugu, Alessia Ciafarone, Maria Grazia Cifone, Davide Pietropaoli and Serena Altamura
Int. J. Mol. Sci. 2026, 27(12), 5356; https://doi.org/10.3390/ijms27125356 - 13 Jun 2026
Viewed by 278
Abstract
Chronic low-grade inflammation is a hallmark of aging and a major driver of metabolic and degenerative diseases. While systemic immune dysfunction has been widely investigated, the contribution of barrier tissues to persistent inflammatory signaling remains incompletely defined. The oral mucosa represents a uniquely [...] Read more.
Chronic low-grade inflammation is a hallmark of aging and a major driver of metabolic and degenerative diseases. While systemic immune dysfunction has been widely investigated, the contribution of barrier tissues to persistent inflammatory signaling remains incompletely defined. The oral mucosa represents a uniquely exposed barrier, continuously challenged by microbial, mechanical, and metabolic stressors and characterized by a specialized immune architecture. Here, we synthesize current evidence supporting the oral barrier as an active immunometabolic interface linking local immune activation to systemic inflammatory tone. Spatially organized epithelial, neutrophil, and antigen-presenting cell (APC) compartments coordinate immune responses tightly coupled to metabolic reprogramming, including hypoxia-inducible factor-1α (HIF-1α)-dependent glycolysis and mitochondrial reactive oxygen species (mtROS) production. In parallel, the oral microbiota provides ligands and metabolites such as lipopolysaccharide (LPS), short-chain fatty acids (SCFAs), and succinate, which activate pattern-recognition receptors (PRRs), including toll-like receptors (TLRs) and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, thereby sustaining nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-mediated inflammatory signaling. Barrier disruption and dysbiosis promote microbial translocation and persistent innate immune activation, while saliva and gingival crevicular fluid facilitate systemic dissemination of inflammatory mediators. Overall, sustained immunometabolic engagement at the oral barrier emerges as a key driver of chronic low-grade systemic inflammation and a potential therapeutic target in inflammaging. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Oral Immunology)
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17 pages, 1977 KB  
Article
Succinate Prevents Mice Obesity by Enhancing Brown Adipocyte Thermogenesis via the SDH-METTL3-HIF1A Pathway
by Yaojun Luo, Zimeng Xin, Youhua Liu, Ruiti Ren and Xinxia Wang
Int. J. Mol. Sci. 2026, 27(12), 5348; https://doi.org/10.3390/ijms27125348 - 13 Jun 2026
Viewed by 187
Abstract
Succinate, a tricarboxylic acid (TCA) cycle intermediate, is the essential signal molecule that links metabolic signals and inflammation. Dietary succinate supplementation has been reported to prevent obesity induced by a high-fat diet (HFD). However, the underlying mechanism remains elusive. Here, we found that [...] Read more.
Succinate, a tricarboxylic acid (TCA) cycle intermediate, is the essential signal molecule that links metabolic signals and inflammation. Dietary succinate supplementation has been reported to prevent obesity induced by a high-fat diet (HFD). However, the underlying mechanism remains elusive. Here, we found that dietary succinate elevated the serum succinate levels. Meanwhile, we found succinate increased methyltransferaselike 3 (METTL3) protein expression in brown adipocytes, thereby elevating N6-methyladenosine (m6A) levels in Hypoxia-inducible factor1-alpha (Hif1a) mRNA. Hif1a mRNA is recognized by the m6A-binding protein YTH domain-containing family protein 1 (YTHDF1), facilitating HIF1A protein expression. HIF1A activates the transcription of thermogenic genes, ultimately increasing brown adipose energy expenditure. Together, our research provided new insights into the effect of succinate on m6A modification in brown adipose tissue thermogenesis. Full article
(This article belongs to the Section Molecular Biology)
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21 pages, 23940 KB  
Article
Mitochondrial Signaling and Ultrastructure in the Myocardium During Long-Term Adaptation to Hypoxia
by Natalya Khmil, Elita Germanova, Lyubov Pavlik, Galina Mironova and Ludmila Lukyanova
Int. J. Mol. Sci. 2026, 27(12), 5331; https://doi.org/10.3390/ijms27125331 - 12 Jun 2026
Viewed by 201
Abstract
In the myocardium of rats of two phenotypes (low and high resistance to hypoxia), the dependence of the reaction of catalytic subunits of mitochondrial enzyme complexes I–V and the severity of ultrastructural changes in mitochondria upon exposure to repeated hypoxia (20 days—three daily [...] Read more.
In the myocardium of rats of two phenotypes (low and high resistance to hypoxia), the dependence of the reaction of catalytic subunits of mitochondrial enzyme complexes I–V and the severity of ultrastructural changes in mitochondria upon exposure to repeated hypoxia (20 days—three daily hourly exposures to hypoxic mixtures of −14% O2, 10.5% O2 and 8% O2, equivalent to 3000 m, 5000 m and 7000 m). The dynamics of expression of catalytic subunits of mitochondrial complexes I–V and ultrastructural changes in three subpopulations of mitochondria were analyzed. During the course of exposure to hypoxia (training sessions) each repeated hypoxic exposure under any regimen caused an activation of mitochondrial complex II and mitochondrial complexes III–V. At 14–10.5% O2, this reaction was repeated with each hypoxic exposure during 8–12 training sessions. After 20 sessions, ATP synthesis returned to its initial level, indicating the completion of adaptation. These changes correlated with optimization of the mitochondrial ultrastructure, which was most pronounced at 14% O2. On the contrary, at 8% O2 under conditions of inhibition of succinate dehydrogenase (mitochondrial complex II), ATP synthesis was suppressed; and pronounced structural disorders of mitochondria developed. Thus, we have demonstrated that mitochondrial enzymes and the ultrastructure of subpopulations of myocardial mitochondria are informative indicators of the functional and metabolic state of the heart. Full article
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15 pages, 1144 KB  
Article
Comprehensive Characterization of the Bioactive Profile in Spirulina platensis Vinegar
by Elif Yildiz, Ozan Gurbuz, Tugce Boga Demirel, Kubra Topaloglu Gunan and Metin Guldas
Foods 2026, 15(12), 2097; https://doi.org/10.3390/foods15122097 - 11 Jun 2026
Viewed by 282
Abstract
This study evaluated the bioactive properties of Spirulina platensis-based vinegar (SV) compared to apple vinegar (AV), focusing on organic acids, phenolic compounds, antioxidant capacity, and in vitro bioaccessibility. SV showed a significantly enhanced bioactive profile, with higher levels of key compounds such [...] Read more.
This study evaluated the bioactive properties of Spirulina platensis-based vinegar (SV) compared to apple vinegar (AV), focusing on organic acids, phenolic compounds, antioxidant capacity, and in vitro bioaccessibility. SV showed a significantly enhanced bioactive profile, with higher levels of key compounds such as gallic acid (86.99 ± 0.14 mg/L), succinic acid (15,859.43 ± 147.24 mg/L), and shikimic acid (147.13 ± 1.37 mg/L), indicating active fermentation-driven biotransformation. In addition, phytic acid present in Spirulina powder (494.43 ± 5.57 mg/L) was completely eliminated after fermentation. Importantly, SV exhibited significantly higher bioaccessible antioxidant capacity (25.68 ± 0.06 µmol TE/mL) than AV (8.68 ± 0.04 μmol TE/mL) based on the ABTS assay. Principal component analysis confirmed that organic acids were the main drivers of bioactive potential, while phenolics contributed to compositional differentiation. Overall, these results indicate that Spirulina platensis is a promising raw material for producing functional vinegar with enhanced bioactivity and bioaccessibility. Full article
(This article belongs to the Topic Advances in Analysis of Food and Beverages, 2nd Edition)
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34 pages, 11920 KB  
Review
Biodegradable Polyester–Starch Composite Films Functionalized with Phenolic Compounds: Advances, Challenges, and Prospects for Sustainable Active Packaging
by Bongsoo Shin, Ajit Kumar Singh, Nattinee Bumbudsanpharoke and Seonghyuk Ko
Polymers 2026, 18(12), 1437; https://doi.org/10.3390/polym18121437 - 9 Jun 2026
Viewed by 398
Abstract
The growing demand for sustainable food packaging has intensified interest in biodegradable materials that can reduce environmental impact while preserving food quality. Among these materials, biodegradable polyester–starch composite films functionalized with phenolic compounds have gained attention as promising active packaging systems. They combine [...] Read more.
The growing demand for sustainable food packaging has intensified interest in biodegradable materials that can reduce environmental impact while preserving food quality. Among these materials, biodegradable polyester–starch composite films functionalized with phenolic compounds have gained attention as promising active packaging systems. They combine the melt processability and structural stability of polyesters, such as poly(lactic acid) (PLA), poly(butylene adipate-co-terephthalate) (PBAT), poly(butylene succinate) (PBS), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with the renewability and biodegradability of starch and the antioxidant, antimicrobial, and UV-protective functions of phenolics, such as ferulic acid, quercetin, tea polyphenols, and anthocyanins. This review discusses recent advances in the selection of biodegradable polyesters, starch and thermoplastic starch blending, phenolic incorporation strategies, and their effects on compatibility, morphology, mechanical strength, barrier properties, optical behavior, release, and active packaging functionality. The characteristics and functionality of these films are governed not only by the individual components but also by phase morphology, interfacial interactions, phenolic location, processing conditions, and release control. Key challenges include polyester–starch incompatibility, TPS moisture sensitivity, phenolic stability during melt processing, migration safety, controlled release, and industrial scale-up. Collectively, biodegradable polyester–starch films functionalized with phenolic compounds represent a promising route for developing next-generation sustainable active packaging and may contribute to circular economy approaches. Full article
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20 pages, 4289 KB  
Article
Untargeted Metabolomics Reveals Metabolic Changes in Cyperus esculentus L. by Mixed Fermentation of Lacticaseibacillus paracasei and Saccharomyces cerevisiae
by Cailian Wu, Yajie Wang, Minwei Zhang, Nurgul Reheman, Rui Zhang and Xiaoying Zhu
Fermentation 2026, 12(6), 275; https://doi.org/10.3390/fermentation12060275 - 8 Jun 2026
Viewed by 266
Abstract
This study investigated the effects of single-strain fermentation (using Lactobacillus paracasei XY1-4 and Saccharomyces cerevisiae XX1-2) and 1:1 mixed fermentation on the differential metabolites and in vitro cholesterol-lowering activity of Cyperus esculentus L. tuber milk. A non-targeted metabolomics approach based on liquid chromatography-tandem [...] Read more.
This study investigated the effects of single-strain fermentation (using Lactobacillus paracasei XY1-4 and Saccharomyces cerevisiae XX1-2) and 1:1 mixed fermentation on the differential metabolites and in vitro cholesterol-lowering activity of Cyperus esculentus L. tuber milk. A non-targeted metabolomics approach based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied, and the dynamic changes in physicochemical properties and in vitro cholesterol-lowering rates during fermentation were determined to systematically compare the metabolite profiles and functional characteristics of tuber milk samples subjected to single-strain fermentation and mixed fermentation for 12 h and 24 h, respectively. The results showed that a total of 1085 differential metabolites were screened across all fermentation groups under the criteria of VIP ≥ 1, p < 0.05, and FC ≥ 2 or FC ≤ 0.5, which were primarily classified as lipids and lipid-like molecules as well as organic acids and their derivatives. Enrichment analysis of these differential metabolites identified ten metabolic pathways closely associated with fermentation progression and functional activity, including arginine biosynthesis, the tricarboxylic acid (TCA) cycle, and glutathione metabolism. Further correlation analysis demonstrated that key metabolites such as succinic acid and L-glutamic acid were significantly and positively correlated with the in vitro cholesterol-lowering rate. This study clarifies the effects of different fermentation treatments on the metabolome and functional properties of tuber milk, laying a solid theoretical foundation for the development and quality optimization of functional fermented Cyperus esculentus L. products. Full article
(This article belongs to the Topic Fermented Food: Health and Benefit, 2nd Edition)
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30 pages, 13821 KB  
Review
Effects of High-Altitude Environments on Gut Microbiota and Their Mechanisms in Immune Regulation and High-Altitude Adaptation
by Zhipeng Lu, Guojing Chen, Mingyang Chang, Ningning Wang, Tiantian Xia, Yunan Zhang, Gaoyuan Xu, Qianqian Zhao, Pan Shen, Wei Zhou, Zhexin Ni and Yue Gao
Int. J. Mol. Sci. 2026, 27(11), 5096; https://doi.org/10.3390/ijms27115096 - 4 Jun 2026
Viewed by 280
Abstract
High-altitude environments, characterized by hypoxia, low temperature, and intense ultraviolet radiation, profoundly disrupt host intestinal homeostasis and reshape the gut microbiota, thereby influencing immune regulation and acclimatization. This review systematically summarizes the dynamic compositional and functional changes in the gut microbiota in high-altitude [...] Read more.
High-altitude environments, characterized by hypoxia, low temperature, and intense ultraviolet radiation, profoundly disrupt host intestinal homeostasis and reshape the gut microbiota, thereby influencing immune regulation and acclimatization. This review systematically summarizes the dynamic compositional and functional changes in the gut microbiota in high-altitude natives, immigrant populations, short-term visitors, and relevant animal models. Current evidence indicates that long-term high-altitude adaptation is associated with directional microbial remodeling, including the enrichment of anaerobic and short-chain fatty acid (SCFA)-associated taxa, which may support energy metabolism and immune homeostasis. In contrast, acute high-altitude exposure more readily induces dysbiosis, impairs intestinal barrier integrity, and promotes the translocation of endotoxins and bioactive metabolites. Mechanistically, the gut microbiota and its metabolites participate in high-altitude adaptation and high-altitude-related disease pathogenesis by modulating barrier function, inflammatory responses, oxidative stress, and immune signaling, and by mediating interorgan communication—characterized by metabolite-driven systemic inflammation or tolerance—through the gut–lung, gut–heart, gut–brain, gut–kidney, and gut–testis axes. SCFAs, bile acids, amino acid-derived metabolites, and succinic acid may control immune homeostasis and inflammatory responses through pathways including TLR4/NF-κB and NLRP3. Although the causal relationships, core microbial effectors, and population-specific heterogeneity remain incompletely defined, microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, have shown promise for promoting acclimatization and preventing high-altitude-related disorders. Overall, this review provides an integrated framework linking environmental stress, gut microbial ecology, and host immune–metabolic adaptation at high altitude, and highlights future directions for mechanistic and translational research in high-altitude medicine. Full article
(This article belongs to the Section Molecular Microbiology)
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15 pages, 4422 KB  
Article
Integrating Genome-Scale Metabolic Modeling with Machine Learning Improves Gene Essentiality Prediction in Triple-Negative Breast Cancer
by Bo Kyung Kim, Changdai Gu, Mohamed El-Agamy Farh and Jae Yong Ryu
Int. J. Mol. Sci. 2026, 27(11), 5059; https://doi.org/10.3390/ijms27115059 - 3 Jun 2026
Viewed by 363
Abstract
Triple-negative breast cancer (TNBC) poses a significant therapeutic challenge owing to its aggressiveness and limited treatment options. Here, we integrated genome-scale metabolic modeling with machine learning to improve gene essentiality prediction and identify candidate therapeutic targets for TNBC. Cell-line-specific genome-scale metabolic models were [...] Read more.
Triple-negative breast cancer (TNBC) poses a significant therapeutic challenge owing to its aggressiveness and limited treatment options. Here, we integrated genome-scale metabolic modeling with machine learning to improve gene essentiality prediction and identify candidate therapeutic targets for TNBC. Cell-line-specific genome-scale metabolic models were reconstructed for 50 breast cancer cell lines using RNA-sequencing from Cancer Dependency Map (DepMap). Metabolic reaction flux distributions derived from minimization of metabolic adjustment (MOMA) were used as features to train a random forest classifier, with DepMap gene dependency scores as ground truth labels. This integrative approach outperformed the MOMA alone for gene essentiality prediction, increasing sensitivity from 0.37 to 0.55. The model identified 57 TNBC-specific essential genes, including Enolase 1 (ENO1), that were missed by MOMA-based prediction. Furthermore, 30 synthetic lethal partners of succinate dehydrogenase subunit A (SDHA) were predicted in TNBC cell lines. This framework demonstrates the utility of combining metabolic modeling with machine learning for identifying context-specific cancer vulnerabilities. Full article
(This article belongs to the Section Biochemistry)
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21 pages, 6130 KB  
Article
Development of Sodium Alginate/Cellulose Nanofiber (SA/CNF)-Based Hydrogels for Enhancing Probiotic Stability
by Hyeon Ji Jeon, Bo Yeong Park, Ju Hyun Min, Gyu Ri Shin, Hye Min Jeong, Kwang Yong Seol, Ju-Hoon Lee, Younghoon Kim, Jungwoo Yang and Young Hoon Jung
Gels 2026, 12(6), 491; https://doi.org/10.3390/gels12060491 - 2 Jun 2026
Viewed by 278
Abstract
Probiotics can promote gut health, but their efficacy is often limited by low viability and metabolic activity in the gastrointestinal (GI) tract. This study aimed to develop protective hydrogels for encapsulating Lactiplantibacillus plantarum CJLP 133 using a composite matrix of sodium alginate (SA) [...] Read more.
Probiotics can promote gut health, but their efficacy is often limited by low viability and metabolic activity in the gastrointestinal (GI) tract. This study aimed to develop protective hydrogels for encapsulating Lactiplantibacillus plantarum CJLP 133 using a composite matrix of sodium alginate (SA) and cellulose nanofibers (CNFs). L. plantarum CJLP 133-loaded hydrogel beads were fabricated via the ionic gelation technique using an optimized formulation of SA and CNF. Scanning electron microscopy revealed that CNF integration improved spherical morphology with reduced surface cracking. Fourier transform infrared spectroscopy confirmed the formation of intermolecular hydrogen bonds between SA and CNF. CNF integration also reduced gumminess and chewiness, resulting in a softer texture. The survival rate of L. plantarum CJLP 133 remained high following thermal exposure and freeze-drying. The in vitro GI delivery system demonstrated a protective swelling profile in stimulated gastric fluid and a targeted, highly efficient release profile in stimulated intestinal fluid. Finally, the 3% SA + 0.5% CNF hydrogel with L. plantarum CJLP 133 exhibited significant synbiotic effects, enhancing probiotic growth, intestinal adhesion, and butyrate and succinate production. These results suggest that the SA/CNF-based hydrogel is an effective delivery system that ensures the targeted release of probiotics within the GI tract. Full article
(This article belongs to the Special Issue Advanced Gels in the Food System (2nd Edition))
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34 pages, 15394 KB  
Article
Supercritical Solvent Impregnation of Poly(lactic acid) (PLA)-Based Films: Effect of Poly(3-hydroxybutyrate) (PHB) and Poly(butylene succinate) (PBS) on Loading Capacity, Optical Properties and Release Kinetics of Mango Leaf Extract
by Ludisbel León-Marcos, Antonio Montes, Diego Valor, Ignacio García-Casas and Clara Pereyra
Polymers 2026, 18(11), 1377; https://doi.org/10.3390/polym18111377 - 1 Jun 2026
Viewed by 361
Abstract
The present study evaluates the optical and colorimetric properties of Polylactic acid (PLA)-based films blended with Poly(3-hydroxybutyrate) (PHB) and Poly(butylene succinate) (PBS) and impregnated with mango leaf extract (MLE) using supercritical solvent impregnation (SSI) under different operating conditions (pressure: 10–30 MPa; temperature: 35–55 [...] Read more.
The present study evaluates the optical and colorimetric properties of Polylactic acid (PLA)-based films blended with Poly(3-hydroxybutyrate) (PHB) and Poly(butylene succinate) (PBS) and impregnated with mango leaf extract (MLE) using supercritical solvent impregnation (SSI) under different operating conditions (pressure: 10–30 MPa; temperature: 35–55 °C). Additionally, the relationship between impregnation load (IL) and color properties, as well as the release kinetics of the impregnated compounds, was investigated. The incorporation of PHB and PBS into the PLA matrix prior to impregnation led to a slight increase in the b* parameter (from 1.64 to 2.61), indicating a tendency toward yellowish tones. After SSI, all films exhibited noticeable color changes, with a shift toward yellowish-green hues and a decrease in lightness, regardless of processing conditions. Statistical analysis confirmed that polymer composition and its interaction with pressure and temperature significantly affected color properties (p-value < 0.001). The addition of PHB and PBS, as well as MLE impregnation, enhanced UV-barrier properties, while also modifying film transparency and opacity. In particular, PLA-PBS films showed higher opacity (more than 20 times) and lower transparency compared to neat PLA. These films also exhibited the highest IL values (2.41–4.75 mg MLE/100 mg polymer). Multivariate regression analysis demonstrated a strong correlation between CIELAB parameters (L*, a*, and b*) and IL (R2 > 85%, p-value < 0.001). Release studies in a food simulant showed partial release profiles, well described by Peleg’s model (R2 > 0.90). Furthermore, Korsmeyer–Peppas model fitting yielded diffusion exponents (n < 0.5), indicating quasi-Fickian diffusion mechanisms governing the release process. Full article
(This article belongs to the Section Polymer Physics and Theory)
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