Search Results (7,571)

Oxidative stress occurs within bovine when exposed to harmful stimuli, accompanied by substantial accumulation of reactive oxygen species. Without timely clearance, these reactive oxygen species attack vascular endothelial cells, concurrently inducing extensive production of lipid peroxides within the vascular endothelium, and thereby triggering ferroptosis. Aspirin eugenol ester (AEE) showed pharmacological activity against oxidative stress-induced vascular endothelial damage. However, whether it could alleviate vascular endothelial damage by inhibiting ferroptosis remains unclear. This study aimed to evaluate the effects of AEE on vascular endothelial ferroptosis and elucidate its underlying molecular mechanisms. This study established vascular endothelial damage models in vitro and in vivo to explore the ability of AEE to inhibit ferroptosis and oxidative stress by measuring ferroptosis- and oxidative stress-related biomarkers. Transcriptomic and network pharmacology analyses were performed to identify AEE-regulated pathways and key targets. Validation of the pathways were conducted using molecular docking, cellular thermal shift assay, and specific protein agonists/inhibitors. AEE inhibited oxidative stress and ferroptosis in bovine aortic endothelial cells induced by hydrogen peroxide (H₂O₂) or RSL3 via suppressing the upregulation of ferroptosis-related genes and enhancing the expression of antioxidant genes. Transcriptomic and network pharmacology analyses identified JNK as a core target of AEE in regulating ferroptosis. JNK agonists enhanced H₂O₂-induced ferritinophagy; on the contrary, JNK inhibitors alleviated it. AEE suppressed H₂O₂-induced phosphorylation of JNK/c-Jun and ferritinophagy. In a carrageenan-induced rat aortic vascular endothelial damage model, AEE alleviated vascular endothelial damage and ferroptosis-related gene changes, promoted antioxidant gene expression, and inhibited JNK/c-Jun phosphorylation and ferritinophagy. AEE inhibited vascular endothelial ferroptosis by enhancing antioxidant ability, blocking downstream ferritinophagy, and reducing ferrous ion release. Full article

Objectives: Shen-Ling-Bai-Zhu-San (SLBZS) is a classical traditional Chinese herbal formula with spleen-invigorating and dampness-resolving properties. Recent pharmacological studies suggest its potential to regulate immune and metabolic disorders. Type 2 diabetes mellitus (T2D) and ulcerative colitis (UC) often coexist as comorbidities characterized by chronic inflammation, microbial imbalance, and insulin dysregulation, yet effective therapies remain limited. This study aimed to investigate the molecular mechanisms through which SLBZS may benefit T2D–UC comorbidity. Methods: An integrative multi-omics strategy was applied, combining network pharmacology, structural bioinformatics, and ensemble molecular docking–dynamics simulations. These complementary approaches were used to identify SLBZS bioactive compounds, predict their putative targets, and examine their interactions with disease-related biological networks. Results: The analyses revealed that flavonoids in SLBZS act on the SLC6A14/PI3K–AKT signaling axis, thereby modulating immune responses and improving insulin sensitivity. In addition, SLBZS was predicted to regulate the NF-$\kappa$B/MAPK signaling pathways, key hubs linking inflammation and metabolic dysfunction in T2D–UC. These dual actions suggest that SLBZS can intervene in both inflammatory and metabolic processes. Conclusions: SLBZS demonstrates promising therapeutic potential for T2D–UC by targeting interconnected immune–metabolic networks. These findings not only provide mechanistic insights bridging traditional therapeutic concepts with modern pharmacology but also establish a theoretical basis for future experimental validation and clinical application. Full article

In recent years, the scientific community has increasingly delved into the study of the interaction between the nervous system and tumors, revealing that the nervous system not only regulates bodily functions under physiological conditions, but also assumes a vital part in the emergence and progression of tumors. Research has demonstrated that the extensive neural network directly regulates tumor progression and can influence tumors by modulating the tumor microenvironment and immune system. Moreover, tumors induce neural networks to provide favorable conditions for their proliferation and metastasis. In the above process, neurotransmitters play a vital role. They directly act or bind to their receptor, activating various classical signaling pathways, among which are PI3K/AKT, MEK/ERK, and WNT/β-catenin, to facilitate tumor advancement. Therefore, this study systematically reviews the regulatory mechanisms of neurotransmitters and their receptors in the advancement of cancer, along with the utilization of targeted drugs. At the same time, we also analyzed that targeting specific receptor subtypes may produce more significant therapeutic effects in different types of cancer. Additionally, this research further explores the limitations of neurotransmitter-based drugs currently used in clinical cancer treatment. In summary, the field of cancer neuroscience is rapidly advancing, constantly revealing the regulatory effects of neurotransmitters on tumor progression and their specific molecular mechanisms, providing broad application prospects for future clinical therapy. Full article

Ammonia–coal co-combustion has emerged as a promising strategy for reducing carbon emissions from coal utilization, although its underlying reaction mechanisms remain insufficiently understood. The Chemkin simulation of zero-dimensional homogeneous reaction model and entrained flow reaction model was employed here, and the ROP (rate of production) and sensitivity analysis was performed for analyzing in-depth reaction mechanisms. The nitrogen conversion pathways were revealed, and the mechanisms were simplified. Based on simplified mechanisms, molecular-level reaction pathways and thermochemical conversion networks of nitrogen-containing precursors were established. The results indicate that NO emissions peak at a 30% co-firing ratio, while N₂O formation increases steadily. The NH radical facilitates NO reduction to N₂O, with NH + NO → N₂O + H identified as the dominant pathway. Enhancing NNH formation and suppressing NCO intermediates are key to improving nitrogen conversion to N₂. This paper quantifies the correlation between NO_x precursors such as HCN and NH₃ and intermediates such as NCO and NNH during ammonia–coal co-firing and emphasizes the important role of N₂O. These insights offer a molecular-level foundation for designing advanced ammonia–coal co-combustion systems aimed at minimizing NO_x emissions. Full article

Plants, as sessile organisms, rely on sophisticated gene regulatory networks (GRNs) to adapt to dynamic environmental conditions. Among the central components of these networks are the interconnected pathways of light signaling and circadian rhythms, which together optimize growth, development, and stress resilience. While light and circadian pathways have been extensively investigated independently, their integrative coordination in mediating climate change adaptation responses remains a critical knowledge gap. Light perception via photoreceptors initiates transcriptional reprogramming, while the circadian clock generates endogenous rhythms that anticipate daily and seasonal changes. This review explores the molecular integration of light and circadian signaling, emphasizing how their crosstalk fine-tunes GRNs to balance resource allocation, photomorphogenesis, and stress adaptation. We highlight recent advances in systems biology tools, e.g., single-cell omics, CRISPR screens that unravel spatiotemporal regulation of shared hubs like phytochrome-interacting factors (PIFs), ELONGATED HYPOCOTYL 5 (HY5), and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1). Here, we synthesize mechanistic insights across model and crop species to bridge fundamental molecular crosstalk with actionable strategies for enhancing cropresilience. Moreover, we have tried to discuss agricultural implications in engineering light–clock interactions for the enhancement in crop productivity under climate change scenarios. Through synthesizing mechanistic insights and translational applications, this work will help underscore the potential for manipulating light–circadian networks to promote sustainability in agriculture. Full article

The submandibular glands (SMGs), along with the parotid and sublingual glands, generate the majority of saliva and play critical roles in maintaining oral and systemic health. Despite their physiological importance, long-term therapeutic options for salivary gland dysfunction remain limited, highlighting the need for a deeper molecular understanding of SMG biology, particularly in humans. To address this knowledge gap, we have performed transcriptomic- and epigenomic-based analyses and molecular characterization of the human SMG. Our integrated analysis of multiorgan RNA-sequencing datasets has identified an SMG-enriched gene expression signature comprising 289 protein-coding and 75 long non-coding RNA (lncRNA) genes that include both known regulators of salivary gland function and several novel candidates ripe for future exploration. To complement these transcriptomic studies, we have generated chromatin immunoprecipitation sequencing (ChIP-seq) datasets of key histone modifications on human SMGs. Our epigenomic analyses have allowed us to identify genome-wide enhancers and super-enhancers that are likely to drive genes and regulatory pathways that are important in human SMG biology. Finally, comparative analysis with mouse and human SMG and other tissue datasets reveals evolutionary conserved gene and regulatory networks, underscoring fundamental mechanisms of salivary gland biology. Collectively, this study offers a valuable knowledge-based resource that can facilitate targeted research on salivary gland dysfunction in human patients. Full article

Wnt signaling is an ancient developmental mechanism that drives the initial specification and patterning of the primary axis in many metazoan embryos. Yet, it is unclear how exactly the various Wnt components interact in most Wnt-mediated developmental processes as well as in the molecular mechanism regulating adult tissue homeostasis. Recent work in invertebrate deuterostome sea urchin embryos indicates that three different Wnt signaling pathways (Wnt/β-catenin, Wnt/JNK, and Wnt/PKC) form an interconnected Wnt signaling network that specifies and patterns the primary anterior–posterior (AP) axis. Here, we detail our current knowledge of this critical regulatory process in sea urchin embryos. We also illustrate examples from a diverse group of metazoans, from cnidarians to vertebrates, that suggest aspects of the sea urchin AP Wnt signaling network are deeply conserved. We explore how the sea urchin is an excellent model to elucidate a detailed molecular understanding of AP axis specification and patterning that can be used for identifying unifying developmental principles across animals. Full article

The effects of the La₂O₃/Al₂O₃ mass ratio (L/A-ratio) in electroslag on La yield and the cleanliness of La-containing H13 steel, as well as slag properties were investigated. The slag–steel interaction experiments between slags bearing varying L/A-ratios based on 50wt%CaF₂-20wt%CaO-Al₂O₃-La₂O₃ slag and La-containing H13 steel were conducted. The molecular dynamics (MD) simulation was used to estimate the viscosity, electrical conductivity, and structure of the slag. The results show that La yield increases from 5.3% to 63.2% with L/A-ratio increasing from 0.2 to 5.0 due to the increasing La₂O₃ activity and decreasing Al₂O₃ activity of slag. Thermodynamic analysis indicates that La₂O₃ content should be higher than 23.9 wt% to ensure desirable La treatment effect. The desulfurization and deoxidation ability of slag are enhanced with increasing L/A-ratio. In addition, the phosphorus and arsenic content in steel decrease when the L/A-ratio reaches 5.0, and the removal rates are 20.0% and 33.3%, respectively. This is attributed to the formation of La-O-As-S-P inclusions. The MD simulation results indicate that the increasing L/A-ratio leads to a decrease in viscosity and increase in electrical conductivity. The mechanism is that the increasing concentration of free oxygen simplifies the aluminate network and increases the mobility of ions in slag. Full article

Walnuts (Juglans regia L.) are an economically important woody crop, but spring frost poses a serious threat to their growth and productivity. However, the molecular mechanisms underlying walnut responses to freezing stress remain largely unknown. In this study, transcriptome analyses were performed on cold-tolerant and cold-sensitive walnut varieties subjected to freezing stress. A total of 9611 differentially expressed genes (DEGs) responsive to freezing stress were obtained, of which 2853 were common up-regulated and 2880 were common down-regulated in both varieties. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed 15 significantly enriched pathways in both varieties, including flavonoid biosynthesis. A simplified walnut flavonoid biosynthesis pathway was constructed, encompassing 36 DEGs encoding 13 key enzymes, demonstrating that flavonoid biosynthesis in walnut is significantly activated under freezing stress. Furthermore, weighted gene co-expression network analysis (WGCNA) identified a regulatory network centered on the JrCBF genes and uncovered 34 potential interacting genes. Collectively, these findings provide novel insights into the molecular responses of walnut to freezing stress and establish a foundation for elucidating the mechanisms underlying walnut cold tolerance. Full article

Sugar beet pulp (SBP), a byproduct of the sugar industry, presents significant potential for enhancing economic benefits and promoting sustainable development through its comprehensive utilization. SBP is rich in fiber, with its soluble dietary fiber (SDF) constituting a high-value component. The initial step in the preparation of SDF involves the drying of fresh SBP. This study compares the effects of hot air and microwave drying on the composition, structure, and physicochemical properties of SDF in SBP. Technologies such as gel permeation chromatography, gas chromatography–mass spectrometry, Fourier transform infrared spectroscopy, scanning electron microscopy, and Zeta potential analysis were employed. Results indicated that microwave drying enhanced sugar components in SDF, reduced polysaccharide molecular weight, and formed a uniform and porous microstructure. This resulted in a higher Zeta potential (−24.76 mV) and increased water holding capacity (5.01 g/g). Hot air-dried samples preserved a more intact cell wall network, exhibiting higher swelling capacity (5.18 mL/g). The study demonstrated how both drying methods differentially regulated SDF quality from sugar beet pulp, suggesting that drying process selection should be based on specific application needs. Full article

Mesoporous silica nanoparticles have been synthesized through sol–gel synthesis in basic conditions. Gemini surfactants having urea in the headgroups were used as pore-forming agents. The effect of the spacer length of the surfactant on the particle morphology was studied on the sub-micrometer and nanometer scales using nitrogen porosimetry, small-angle X-ray scattering (SAXS), ultra-small-angle neutron scattering, and scanning and transmission electron microscopy (SEM, TEM). Depending on the spacer, spherical and/or cylindrical nanoparticles formed in different proportions, as revealed by statistical analysis of SEM micrographs. All prepared materials showed the hexagonal pore structure characteristic of the MCM-41 molecular sieves, with the exception of the sample prepared using the gemini surfactant with the shortest spacer length. The influence of the spacer length on the lattice parameter of the pore network, as well as the average size of the ordered domains, has been assessed by SAXS and TEM. Detailed analysis of the TEM images revealed a spread of the lattice parameter in a range of 10–20%. The broadening of the diffraction peaks was shown to be due to the combination of the effects of the finite domain size and the variance of the lattice parameter across the crystalline domains. The structural differences between the silica gels synthesized with the different surfactants were related to the variation of the micelle morphologies, reported in previous light scattering and small-angle scattering experiments. No connection could be revealed between the micelle shape and size and the pore sizes, showing that surfactants with a broad range of spacer lengths can equally well be used for the preparation of MCM-41 materials. Full article

The remediation of contaminated soils is essential for restoring land productivity and soil health. Pteris vittata L., an arsenic hyperaccumulator, has been widely used for phytoremediation, yet its ecological effects on soil systems remain insufficiently understood. In this field study, we evaluated the influence of Pteris vittata L. remediation on soil physico-chemical properties, microbial diversity, and molecular ecological networks. The results showed that long-term arsenic contamination significantly reduced soil total carbon, total nitrogen, and available phosphorus, simplified bacterial network structures, and markedly altered the keystone taxa that maintain microbial interactions. In contrast, soils under Pteris vittata L. remediation exhibited higher nutrient availability, greater bacterial diversity, and more complex microbial networks than contaminated soils, indicating partial recovery of ecosystem functions. These findings demonstrate that Pteris vittata L. remediation can mitigate arsenic-induced soil degradation and provide an important scientific basis for assessing the long-term impacts of arsenic contamination and the role of remediation measures in soil health evolution. Full article

Angiogenesis, the formation of new blood vessels from existing vasculature, is regulated by a balance between pro- and anti-angiogenic factors. In adults, this process typically occurs in response to inflammation, wound healing, and neoplastic growth. Uniquely, the female reproductive system undergoes cyclical and repetitive angiogenesis with folliculogenesis, decidualization, implantation, and embryo development throughout the reproductive cycle. Ovarian angiogenesis involves a coordinated network of signaling pathways and molecular factors. Vascular endothelial growth factor (VEGF) is the primary driver of this process, supported by other regulators such as fibroblast growth factor (FGF) and hypoxia-inducible factor (HIF). Understanding the molecular mechanisms that govern ovarian angiogenesis is essential for developing new diagnostic and therapeutic approaches in reproductive medicine. Vascular dysfunction and impaired angiogenesis are key contributors to various ovarian disorders and infertility, including polycystic ovary syndrome (PCOS). Therefore, in-depth studies of ovarian vascularization are crucial for identifying the pathophysiology of these conditions and guiding the development of effective treatments. Advancing knowledge in this area holds significant potential for innovation in both medicine and biotechnology. Full article

Background and Aims: Little is known about metabolic dysfunction-associated steatotic liver disease (MASLD) as a risk factor for hepatocellular carcinoma (HCC) in non-cirrhotic (HCC-NC) patients. In-house developed mouse models with defective lipid-metabolizing enzyme long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD), coded by hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA) gene, result in MASLD (steatosis) without cirrhosis leading to HCC-NC. The aims of the current investigations are to assess molecular markers and the associated molecular events that may lead to HCC-NC. Methods: cDNA array study of HCC patients was conducted to assess the expression of HADHA transcripts. Differentially expressed proteins identified between wild-type (WT) and heterozygous mice with no cancer (HT) from a previous study were subjected to Ingenuity Pathway Analysis (IPA). Western blotting was performed to assess the expression of proteins. Results: IPA of the differentially expressed proteins between WT and HT mice results in two biological networks (network 1 and network 2), which pointed to an important role of p53 in HCC-NC. Validation of the levels of MDM2 and p53 also highlights the role of MDM2-p53 axis in HCC-NC. All the focus molecules in network 1 and network 2 are either presented as tumor suppressor/promoter of carcinogenesis or serum markers for early HCC diagnosis. The hepatotoxicity report from IPA further identified four functional groups including liver steatosis, glutathione depletion, hepatocellular carcinoma, and liver hyperplasia/hyperproliferation. Conclusions: This study suggests that impaired fatty oxidation may play a role in the development of HCC associated with steatosis but without cirrhosis (HCC-NC). Defective LCHAD is a novel etiology for HCC. Full article

The accurate prediction of herb–target interactions is essential for the modernization of traditional Chinese medicine (TCM) and the advancement of drug discovery. Nonetheless, the inherent complexity of herbal compositions and diversity of molecular targets render experimental validation both time-consuming and labor-intensive. We propose a graph neural network model, MAMGN-HTI, which integrates metapaths with attention mechanisms. A heterogeneous graph consisting of herbs, efficacies, ingredients, and targets is constructed, where semantic metapaths capture latent relationships among nodes. An attention mechanism is employed to dynamically assign weights, thereby emphasizing the most informative metapaths. In addition, ResGCN and DenseGCN architectures are combined with cross-layer skip connections to improve feature propagation and enable effective feature reuse. Experiments show that MAMGN-HTI outperforms several state-of-the-art methods across multiple metrics, exhibiting superior accuracy, robustness, and generalizability in HTI prediction and candidate drug screening. Validation against literature and databases further confirms the model’s predictive reliability. The model also successfully identified herbs with potential therapeutic effects for hyperthyroidism, including Vinegar-processed Bupleuri Radix (Cu Chaihu), Prunellae Spica (Xiakucao), and Processed Cyperi Rhizoma (Zhi Xiangfu). MAMGN-HTI provides a reliable computational framework and theoretical foundation for applying TCM in hyperthyroidism treatment, providing mechanistic insights while improving research efficiency and resource utilization. Full article