Search Results (5,254)

Noni juice polysaccharides demonstrate promising hypoglycemic activity, but their high molecular weight restricts bioavailability. This study established a controlled degradation approach to optimize the functional properties of Noni juice polysaccharides. Molecular characterization demonstrated that the degraded Noni juice polysaccharides (DNJPs, Mw 191.8 kDa) retained the core monosaccharide composition, while exhibiting enhanced solubility. In vitro experiments with insulin-resistant HepG2 cells showed that DNJPs (0.5–2 mg/mL) significantly enhanced glucose consumption (p < 0.01) and mitigated oxidative stress by upregulating antioxidant enzymes (SOD, CAT, and GSH-Px) and decreasing malondialdehyde (MDA) levels. DNJPs activated the PI3K/AKT-Nrf2-GSK3β signaling axis through a multifaceted mechanism involving the following: upregulating the phosphorylation levels of PI3K and AKT; enhancing Nrf2 nuclear translocation, which in turn promotes the expression of downstream targets such as HO-1 and NQO1; inhibiting GSK3β activity; and suppressing FOXO1-mediated gluconeogenesis. These findings underscore DNJPs as promising functional food ingredients that modulate two key pathways to improve glucose metabolism. Full article

To investigate the impacts of dietary Bacillus-based probiotics and yeast-derived prebiotics on the hepatic transcriptome profile, 500 Hisex White laying hens were randomly allotted into five dietary treatments from 37 to 52 weeks of age: control; control + Bacillus subtilis; control + Bacillus subtilis and Bacillus licheniformis; control + Bacillus coagulans; and control + Saccharomyces cerevisiae yeast cell wall. Transcriptome analysis revealed a substantial number of differentially expressed genes exclusively between the control and prebiotic groups, identifying 2221 genes (FDR ≤ 0.05), with 980 genes upregulated (log₂ fold change 0.69 to 24.62) and 1241 downregulated (log₂ fold change −0.74 to −26.46). The top 10 upregulated KEGG pathways included protein export, glycerophospholipid metabolism, tryptophan metabolism, amino acid biosynthesis, alanine, aspartate, and glutamate metabolism, cofactor biosynthesis, propanoate metabolism, ABC transporters, 2-oxocarboxylic acid metabolism, and protein processing within the endoplasmic reticulum. In contrast, the most prominently downregulated pathways encompassed fructose and mannose metabolism, hedgehog signaling, PPAR signaling, Notch signaling, GnRH signaling, cell adhesion molecules, cytokine–cytokine receptor interactions, apelin signaling, glycosaminoglycan degradation, and RIG-I-like receptor signaling. These findings advance understanding of the hepatic transcriptomic response to yeast-derived prebiotics and identify key molecular pathways that could be targeted to enhance metabolic function in laying hens. Full article

Myokines are secreted by muscle and play crucial roles in muscle repair and regeneration and also impact diverse physiological effects through crosstalk with other metabolic organs. However, aging is associated with a progressive decline in muscle mass, which in turn leads to reduced myokine secretion. This decline may contribute to the development of sarcopenia, leading to an increased risk of metabolic disorders such as type 2 diabetes. Accordingly, interest in identifying novel myokines and elucidating their biological functions is increasing. In this study, we explored the function of biglycan (BGN), a novel myokine, in aging-related metabolic tissues. BGN levels decreased in the muscle tissue and plasma of older adults and aged mice, whereas exercise intervention restored BGN expression in aged mice. BGN counteracted the expression of atrophy-related genes involved in muscle degradation and mitigated muscle mass loss by regulating AKT/mTOR signaling pathway. Notably, BGN decreased the expression of the senescence marker p21 and senescence-associated secretory phenotype (SASP)-related genes in hepatocytes. Additionally, BGN attenuated senescence-induced lipid accumulation and ROS generation. Our results suggest that BGN has beneficial effects against muscle atrophy and hepatocellular senescence, indicating its potential as a protective factor for age-related diseases. Full article

Astringent persimmons (Diospyros kaki Thunb.) require effective postharvest deastringency treatments due to their high soluble tannin content at harvest. While high CO₂ and ethylene are commonly used to remove astringency, their different effects on fruit firmness and quality require cultivar-specific approaches. This study investigated the transcriptomic and biochemical responses of ‘Daebong’ persimmon to high CO₂ and ethylene treatments during deastringency. Both treatments significantly decreased soluble tannin and total phenolic content, enhancing fruit edibility. However, the firmness was maintained under high levels of CO₂, but it decreased quickly after exposure to ethylene. RNA-Seq analysis identified 2271 differentially expressed genes (DEGs) and revealed distinct transcriptional signatures for each treatment. CO₂ treatment activated hypoxia-responsive genes, stress-related transcription factors (e.g., WRKY, ERF14/26), and components of antioxidant defense (e.g., GSTU17, peroxidases), which contributed to oxidative stress reduction and preservation of firmness. On the other hand, ethylene treatment increased ethylene biosynthesis (ACS), signaling (EIN3-binding F-box), and ripening-related genes (polygalacturonase, laccase, ERF061/113), which promote cell wall degradation and softening. Functional enrichment analysis revealed that various regulatory mechanisms are responsible for the insolubilization of tannins, loss of antioxidants, and changes in firmness. These findings provide new insights into the molecular responses of pollination-constant astringent (PCA) persimmons, particularly the ‘Daebong’ cultivar, to postharvest deastringency treatments for the development of more effective postharvest management strategies. The results suggest that high CO₂ helps maintain fruit quality by promoting stress adaptation and suppressing pathways that lead to softening, whereas ethylene accelerates the ripening process by activating signaling pathways associated with ethylene. Full article

Focal adhesion kinase (FAK) is a crucial protein component of focal adhesions (FAs) and belongs to the cytoplasmic non-receptor protein tyrosine kinase family. FAK primarily regulates adhesion signaling and cell migration and is highly expressed in various tumors, including lung, liver, gastric, and colorectal cancers, as well as in conditions such as acute lung injury (ALI) and pulmonary fibrosis (PF). Recent research on FAK and its small-molecule inhibitors has revealed that targeting FAK provides a novel approach for treating various lung diseases. FAK inhibitors can obstruct signaling pathways, demonstrating anti-tumor, anti-inflammatory, and anti-fibrotic effects. In lung cancer, FAK inhibitors suppress tumor growth and metastasis; in ALI, they exert protective effects by alleviating inflammatory responses and oxidative stress; and in pulmonary fibrosis, FAK inhibitors reduce fibroblast activation and inhibit collagen deposition. The findings demonstrate promising efficacy and an acceptable safety profile in preclinical models. However, these early-stage results require further validation through clinical studies. Additionally, the underlying mechanisms, as well as the toxic effects and side effects, necessitate further in-depth investigation. Some have progressed to clinical trials (Defactinib (Phase II), PF-562271 (Phase I), CEP-37440 (Phase I), PND-1186 (Phase I), GSK-2256098 (Phase II), BI-853520 (Phase I)), offering potential therapeutic targets for lung diseases. Collectively, these findings establish a foundational basis for the advancement of FAK inhibitor discovery. Emerging methodologies, such as PROTAC degraders and combination regimens, demonstrate significant potential for future research. Based on a comprehensive analysis of the relevant literature from 2015 to the present, this review briefly introduces the structure and function of FAK and discusses recent research advancements regarding FAK and its inhibitors in the context of pulmonary diseases. Full article

This study investigated individual/combined nitrogen (N) and potassium (K) deficiencies on ginseng root aroma using GC–MS metabolomics. Four treatments (normal supply, N deficiency (LN), K deficiency (LK), and dual deficiency (LNLK)) were analyzed. Deficiencies impaired growth, mineral accumulation, and induced oxidative stress, suppressing ginsenoside biosynthesis. From 1768 detected VOCs, 304 compounds (rOAV ≥ 1) significantly contributed to aroma. LN inhibited terpenoids (e.g., isoborneol) but upregulated sulfur compounds (e.g., di-2-propenyl tetrasulfide), intensifying pungency. LK enhanced sweet/woody notes (e.g., 2′-acetonaphthone) via flavonoid biosynthesis and toluene degradation. LNLK reduced esters (e.g., benzyl acetate) and terpenes, attenuating floral–balsamic nuances by coordinating aromatic degradation, glutathione metabolism, and ABC transporters. N–K nutrition dynamically shapes ginseng aroma by differentially regulating phenylpropanoid, terpenoid, and sulfur pathways, providing a foundation for precision fertilization and quality improvement. Full article

The escalating climate crisis and unsustainable waste management practices necessitate integrated approaches that simultaneously address energy security and environmental degradation. Hydrogen, with its high energy density and zero-carbon combustion, is a key vector for decarbonization; however, conventional production methods are fossil-dependent and carbon-intensive. This systematic review explores biowaste-to-hydrogen (WtH) technologies as dual-purpose solutions, converting organic waste to clean hydrogen while reducing greenhouse gas emissions and landfill reliance. A comprehensive analysis of different conversion pathways, including thermochemical (gasification, pyrolysis, hydrothermal, and partial oxidation (POX)), biochemical (dark fermentation, photofermentation, and sequential fermentation), and electrochemical methods (MECs), is presented, assessing their hydrogen yields, feedstock compatibilities, environmental impacts, and technological readiness. Systematic literature review methods were employed using databases, such as Scopus and Web of Science, with strict inclusion criteria focused on recent peer-reviewed studies. This review highlights hydrothermal gasification and dark fermentation as particularly promising for wet biowaste streams, like food waste. Comparative environmental analyses reveal that bio-based hydrogen pathways offer significantly lower greenhouse gas emissions, energy use, and pollutant outputs than conventional methods. Future research directions emphasize process integration, catalyst development, and lifecycle assessment. The findings aim to inform technology selection, policymaking, and strategic investment in circular, low-carbon hydrogen production. Full article

Concrete used in high-risk infrastructures must withstand elevated temperatures and thermal shocks. This study investigated the thermal transfer behavior of explosion-proof concrete exposed to 100–400 °C through a combined experimental and numerical approach. X-ray diffraction (XRD) revealed that the dominant crystalline phases remained identifiable across this range, but peak broadening and intensity reduction indicated partial decomposition of hydration products and microstructural disorder. Thermal conductivity reached its maximum of 1.48 W/(m·K) at 100 °C and decreased at higher temperatures due to porosity growth and microcracking, reflecting detrimental alterations in heat conduction pathways. In contrast, the specific heat capacity increased from 963.89 J/(kg·K) at 100 °C to 1122.22 J/(kg·K) at 400 °C, enhancing the material’s heat absorption. Density initially decreased with temperature but showed a temporary rebound at 300 °C due to secondary hydration, before dropping sharply to 1830 kg/m³ at 400 °C. Numerical simulations confirmed that high temperatures reduce surface–core temperature gradients, leading to more uniform but structurally weakened heat transfer. These findings highlight that explosion-proof concrete retains acceptable thermal stability below 200 °C, while significant degradation occurs beyond 300 °C. The novelty of this work lies in integrating experimental thermophysical tests with finite element simulations to link microstructural changes with macroscopic thermal behavior. Practically, the results provide guidance for optimizing concrete formulations and protective strategies in fire- and explosion-prone facilities such as LNG storage units and petrochemical infrastructures. Full article

Jasmonates (JAs) are crucial phytohormones governing plant growth and defense against stresses. This review synthesizes the intricate molecular mechanisms underlying JA crosstalk with key hormones: auxin (AU), gibberellin (GA), abscisic acid (ABA), ethylene (ET), brassinosteroids (BRs), strigolactones (SLs), and salicylic acid (SA). We focus on interactions during development and stress adaptation, highlighting how these range from synergistic (e.g., JA-ABA/ET in defense, JA-AU in root growth) to antagonistic (e.g., JA-SA in pathogen response, JA-GA/BRs in growth processes). Central to this crosstalk are key regulatory nodes like the MYC2 transcription factor and JAZ repressor proteins, which integrate signals through transcription factor networks, targeted protein degradation, and post-translational modifications. By elucidating these molecular pathways, our review establishes a framework for understanding the complex regulatory logic of hormone interactions. Furthermore, it offers insights for the strategic engineering of hormone signaling (e.g., modulating JAZ stability or MYC2 activity) to enhance crop resilience to environmental challenges. Full article

Background/Objectives: Forced degradation studies are critical for identifying potential degradation pathways of monoclonal antibodies (mAbs), particularly under thermal stress. Due to their structural complexity and sensitivity to elevated temperatures, mAbs are prone to fragmentation, aggregation, and post-translational modifications. This study aimed to evaluate and compare the degradation profiles of biosimilar anti-VEGF mAb and its originator counterparts sourced from both the United States (U.S.) and the European Union (EU) under thermal stress conditions. To our knowledge, this represents one of the few studies conducting a direct head-to-head comparability assessment across biosimilar and two geographically sourced originators, integrating orthogonal analytical approaches. Methods: Biosimilar candidate and originator products (U.S. and EU) were incubated at 37 °C and 50 °C for 3, 7, and 14 days. Fragmentation profiles were assessed using validated non-reduced and reduced capillary electrophoresis–sodium dodecyl sulfate (CE-SDS) methods. Additionally, size-exclusion ultra-performance liquid chromatography (SE-UPLC) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) assays were performed on samples stressed for 14 days to provide deeper insights into degradation pathways. Results: Non-reduced CE-SDS analysis indicated a time- and temperature-dependent increase in low-molecular-weight fragments and a corresponding decrease in the intact form, with more pronounced effects observed at 50 °C. Reduced CE-SDS revealed a more rapid increase in total impurity levels at 50 °C, accompanied by a decrease in total light and heavy chain content. SE-UPLC showed enhanced aggregation under thermal stress, more pronounced at 50 °C. LC-MS/MS analysis identified increased asparagine deamidation in the PENNY peptide and pyroglutamic acid formation (pE) at the N-terminus of the heavy chain. Conclusions: The degradation profiles of the biosimilar and originator mAbs were highly comparable under thermal stress, with no significant qualitative differences detected. By applying a multi-tiered analytical characterization technique, this study provides a comprehensive comparability assessment that underscores the robustness of biosimilarity even under forced degradation conditions. Full article

Nearly all eukaryotic proteins are turned over by the ubiquitin (Ub)-26S proteasome system (UPS). Despite its broad cellular roles, only a handful of UPS members, particularly the Ub E3 ligases that specifically recognize a protein for ubiquitylation, have been characterized in plants to date. The challenge arises from the transient recognition and rapid degradation of ubiquitylation substrates by the UPS. To tackle this challenge, the emerging biotinylation-based proximity labeling (PL) offers an exciting tool for enriching transient interactors of Ub E3 ligases. In this study, we examined the efficacy of TurboID in identifying substrates of Arabidopsis Skp1-cullin1-F-box (SCF) ligases. We demonstrate that the Arabidopsis Skp1 Like (ASK)1-TurboID is not fully functioning in planta, which led us to discover a novel antagonism between biotinylation and ubiquitylation in regulating protein stability in vivo. This discovery lowers the effectiveness of PL in ubiquitylome studies. However, using one long-known SCF substrate, phytochrome A, we succeeded to apply its TurboID fusion for complementing the far-red-light response of the phyA-211 null mutant allele, suggesting an efficacy of PL in characterizing single ubiquitylation pathways. This study highlighted a limitation of PL in ubiquitylome studies, discovered a new antagonistic pathway of biotinylation, and developed a theoretical guidance for future PL-based characterization of ubiquitylation pathways. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) serves as a master transcriptional regulator of cellular antioxidant responses through orchestration of cytoprotective gene expression, establishing its significance as a therapeutic target in cerebral pathophysiology. Classical electrophilic NRF2 activators, despite potent activation potential, exhibit paradoxically reduced therapeutic efficacy relative to single antioxidants, attributable to concurrent oxidative stress generation, glutathione depletion, mitochondrial impairment, and systemic toxicity. Although emerging non-electrophilic pharmacological activators offer therapeutic potential, their utility remains limited by bioavailability and suboptimal potency, underscoring the imperative for innovative therapeutic strategies to harness this cytoprotective pathway. Non-pharmacological interventions, including neuromodulation, physical exercise, and lifestyle modifications, activate NRF2 through non-canonical, non-electrophilic pathways involving protein–protein interaction inhibition, KEAP1 degradation, post-translational and transcriptional modulation, and protein stabilization, though mechanistic characterization remains incomplete. Such interventions utilize multi-mechanistic approaches that synergistically integrate multiple non-electrophilic NRF2 pathways or judiciously combine electrophilic and non-electrophilic mechanisms while mitigating electrophile-induced toxicity. This strategy confers neuroprotective effects without the contraindications characteristic of classical electrophilic activators. This review comprehensively examines the mechanistic underpinnings of non-pharmacological NRF2 modulation, highlighting non-electrophilic activation pathways that bypass the limitations inherent to electrophilic activators. The evidence presented herein positions non-pharmacological interventions as viable therapeutic approaches for achieving non-electrophilic NRF2 activation in the treatment of cerebrovascular and neurodegenerative pathologies. Full article

Excessive stress disrupts cardiac homeostasis via complex and multifactorial mechanisms, resulting in cardiac dysfunction, cardiovascular disease, or even sudden cardiac death, yet the underlying molecular mechanisms remain poorly understood. Accordingly, we aimed to elucidate how stress induces calcium dysregulation and contributes to cardiac dysfunction and injury through the nuclear receptor subfamily 3 group c member 1 (NR3C1)/Glomulin (GLMN)/FK506-binding protein 12.6 (FKBP12.6) signaling pathway. Using mouse models of acute and chronic restraint stress, we observed that stress-exposed mice exhibited reduced left ventricular ejection fraction, ventricular wall thickening, elevated serum and myocardial cTnI levels, along with pathological features of myocardial ischemia and hypoxia, through morphological, functional, and hormonal assessments. Using transmission electron microscopy and Western blotting, we found that stress disrupted mitochondrial quality control in cardiomyocytes, evidenced by progressive mitochondrial swelling, cristae rupture, decreased expression of fusion proteins (MFN1/OPA1) and biogenesis regulator PGC-1α, along with aberrant accumulation of fission protein (FIS1) and autophagy marker LC3. At the cellular level, ChIP-qPCR and siRNA knockdown confirmed that stress activates the glucocorticoid receptor NR3C1 to repress its downstream target GLMN, thereby preventing FKBP12.6 ubiquitination and degradation, resulting in calcium leakage and overload, which ultimately impairs mitochondrial quality control and damages cardiomyocytes. In conclusion, our findings reveal that stress induces myocardial damage through NR3C1/GLMN-mediated FKBP12.6 ubiquitination, disrupting calcium homeostasis and mitochondrial quality control, and lay a theoretical foundation for dissecting the intricate molecular network of stress-induced cardiomyopathy. Full article

In addition to its role in angiotensin II (Ang II) production, chymase exhibits various functions, including activation of latent transforming growth factor beta 1 (TGF-β1) and pro-matrix metalloproteinases (MMPs). However, the extent to which these Ang II-independent functions contribute to pathological conditions remains unclear. In this study, we investigated the Ang II-independent roles of chymase in cardiac remodeling and dysfunction. Eighteen male Syrian hamsters, aged 6 weeks and weighing 90–110 g, were used. Exogenous Ang II was administered to a hamster model that mirrors the human chymase-dependent Ang II production pathway, via subcutaneous osmotic mini pumps (2 mg/kg/day) for 4 weeks. A chymase-specific inhibitor, TY-51469 (10 mg/kg/day), was given daily starting 1 day after commencement of Ang II infusion. Evaluation showed that while systolic blood pressure increased significantly, only diastolic dysfunction developed over time. Ang II treatment led to elevated cardiac expression of chymase, TGF-β1, and MMP-2, and increased the number of chymase-positive mast cells, resulting in notable cardiac hypertrophy and fibrosis. TY-51469 effectively suppressed these molecular changes and improved both cardiac structure and diastolic dysfunction, despite continued Ang II exposure. These results suggest that chymase promotes cardiac remodeling and dysfunction not only through Ang II generation but also by activating profibrotic and matrix-degrading factors, such as TGF-β1 and MMP-2. Full article

Feeding a growing global population requires sustainable, innovative, and cost-effective solutions, especially in light of the environmental damage and nutrient imbalances caused by excessive chemical fertilizer use. Microalgae have gained prominence due to their phylogenetic diversity, physiological adaptability, eco-compatible characteristics, and potential to support regenerative agriculture and mitigate climate change. Functioning as biofertilizers, biostimulants, and bioremediators, microalgae accelerate nutrient cycling, improve soil aggregation through extracellular polymeric substances (EPSs), and stimulate rhizospheric microbial diversity. Empirical studies demonstrate their ability to increase crop yields by 5–25%, reduce chemical nitrogen inputs by up to 50%, and boost both organic carbon content and enzymatic activity in soils. Their application in saline and degraded lands further promotes resilience and ecological regeneration. Microalgal cultivation platforms offer scalable in situ carbon sequestration, converting atmospheric carbon dioxide (CO₂) into biomass with potential downstream vaporization into biofuels, bioplastics, and biochar, aligning with circular economy principles. While the commercial viability of microalgae is challenged by high production costs, technical complexities, and regulatory gaps, recent breakthroughs in cultivation systems, biorefinery integration, and strain optimization highlight promising pathways forward. This review highlights the strategic importance of microalgae in enhancing climate resilience, promoting agricultural sustainability, restoring soil health, and driving global bioeconomic transformation. Full article