Search Results (2,799)

Interleukin-33 (IL-33) is an IL-1 family cytokine that functions as an alarmin and contributes to inflammatory responses, immune regulation, and tumor-associated processes through the IL-33/ST2 signaling axis. In this study, IL-33-specific nanobodies were isolated from a synthetic phage display library and further engineered into bivalent tandem formats to improve their binding performance. Five representative monovalent nanobodies showed concentration-dependent binding to IL-33, with SPR-derived K_D values ranging from 3.6 × 10⁻⁸ to 2.81 × 10⁻⁷ M. Among the engineered bivalent constructs, Nb1–Nb2 exhibited the strongest apparent binding affinity, mainly due to a markedly reduced dissociation rate. Competitive SPR analysis indicated that Nb1 and Nb2 show largely compatible binding to IL-33, consistent with distinct or minimally overlapping binding regions, supporting their selection as a hetero-bivalent pair. In a preliminary wound-healing assay using HT-29 colorectal cancer cells, Nb1–Nb2 attenuated IL-33-induced wound closure under low-serum conditions. These results indicate that hetero-bivalent engineering can enhance the apparent binding affinity of IL-33-targeting nanobodies and provide a useful molecular tool for further investigation of IL-33-associated biological responses. Full article

Iron overload disrupts cellular homeostasis and drives ferroptosis through dysregulated iron metabolism. Non-coding RNAs (ncRNAs) are considered as key regulators of various biological functions and targets for a new generation of RNA therapeutics and biomarkers. However, few studies have investigated the regulatory roles of ncRNAs, particularly competitive endogenous RNAs (ceRNAs) in iron overload. This study performed whole-transcriptome sequencing to characterize the ceRNA network in ferric ammonium citrate (FAC)-induced iron-overloaded HT-1080 fibrosarcoma cells. A total of 208 differentially expressed mRNAs, 83 lncRNAs, and 170 circRNAs (q < 0.05) were identified, with hierarchical clustering revealing distinct expression patterns between control and iron-treated groups. KEGG enrichment implicated vitamin B6 metabolism (q < 0.001) and lysine degradation (q < 0.001) as key disrupted pathways. ceRNA network was conducted and further demonstrated lncRNA/circRNA-mediated regulation of ferroptosis genes via shared miRNA response elements. Notably, LINC-PINT-232 was implicated in the regulation of both ferritin heavy chain (FTH) and sequestosome 1 (SQSTM1), two ferroptosis-associated mRNAs. FTH upregulation mitigates iron toxicity through ferroxidase activity, while SQSTM1 modulates lipid peroxidation in ferroptosis. These findings provide a preliminary transcriptomic landscape for hypothesis generation regarding ncRNA-mediated regulatory mechanisms in iron overload-induced ferroptosis and offer a computational foundation for future functional and therapeutic investigations. Full article

This study elucidates the multi-targeted antineoplastic mechanisms of Parkia speciosa empty pod extract (PSET) against HCT-116 and HT-29 colorectal cancer (CRC) cells through integrated transcriptomic and proteomic analyses. Phytochemical profiling indicates that PSET is rich in bioactive metabolites, notably quercetin, rutin, and pyrogallol, which orchestrate its profound ability to inhibit tumor proliferation, migration, and invasion. Transcriptomic data revealed that PSET profoundly suppresses the oncogenic Wnt/β-catenin signaling axis while simultaneously activating p53-mediated cell cycle arrest. Complementary proteomic profiling uncovered critical metabolic vulnerabilities, demonstrating that PSET abrogates the Warburg effect by disrupting key glycolytic enzymes (e.g., ENO1, GAPDH, LDHA), thereby inducing metabolic starvation. Furthermore, the extract precipitated a catastrophic collapse of the cytoskeletal architecture and downregulated epithelial–mesenchymal transition (EMT) markers, effectively paralyzing the cells’ metastatic machinery. The integrated transcriptomic and proteomic signatures also highlighted an irrecoverable state of cellular stress, characterized by an overwhelming unfolded protein response and dysregulated RNA splicing, ultimately driving the cells toward apoptosis. In conclusion, this integrated omics approach provides robust molecular validation that PSET systemically dismantles colorectal cancer survival networks, highlighting its strong potential as a natural, multi-targeted therapeutic agent. Full article

Colorectal cancer is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths, while its resistance to treatment continues to represent a major therapeutic challenge. In the present study, a series of phenothiazine derivatives, including hybrids containing a 1,2,3-triazole linker and the zidovudine (AZT) fragment, were synthesized and evaluated for their anticancer activity against colorectal cancer cell lines HCT116 and HT-29 as well as non-cancerous BEAS-2B cells. Cytotoxic activity was determined using the Alamar Blue assay, while the mechanisms of action were investigated by flow cytometric analysis of apoptosis, cell cycle progression, and reactive oxygen species (ROS) generation. Additionally, changes in the expression of genes associated with apoptosis, oxidative stress, and DNA damage response were analyzed by RT-qPCR. The obtained results demonstrated that AZT-containing derivatives exhibited stronger anticancer activity than non-conjugated phenothiazine analogs. Compounds A9–A12 induced pronounced apoptosis and significant disturbances in cell cycle progression, particularly in HCT116 cells. Among the analyzed derivatives, compound A9 displayed the most favorable overall biological profile, combining strong proapoptotic and cytotoxic activity with relatively high selectivity toward cancer cells and moderate effects on non-cancerous cells. The results indicate that molecular hybridization of phenothiazine derivatives with the AZT scaffold represents a promising strategy for the development of novel anticancer agents targeting colorectal cancer. Full article

Background/Objectives: Primary thyroid lymphoma (PTL), including diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, share substantial overlap in ultrasound appearance with Hashimoto’s thyroiditis (HT), making preoperative differentiation challenging. This study aims to develop and validate a deep learning model based on B-mode ultrasound (BMUS) and color Doppler ultrasound (CDUS) for image-level differentiation of DLBCL, MALT lymphoma, and HT. Methods: This retrospective single-center study included 1294 ultrasound images from 290 patients (313 lesions) who underwent preoperative ultrasound examination at West China Hospital between September 2002 and September 2024. All images from the same lesion were assigned to the same data partition, and the dataset was split at the lesion level into training and test sets at an 8:2 ratio. A Frequency-Adaptive WT-ResNet model incorporating wavelet transform convolution and a frequency-adaptive gating mechanism was developed. The primary analysis was performed at the image level. The performance of the model was compared with that of three ultrasound physicians with different levels of experience. Grad-CAM was used for visual interpretation. An exploratory external validation was performed using an independent dataset from Sun Yat-sen Memorial Hospital. Results: In the test set, the model achieved a macro-average AUC of 0.927 (95% CI: 0.889–0.960), with class-specific AUCs of 0.899 for DLBCL, 0.946 for MALT lymphoma, and 0.937 for HT. The macro-average balanced accuracy was 0.866, compared with 0.827 for that of the best-performing senior physician. The exploratory validation set yielded a macro-average AUC of 0.796 (95% CI: 0.686–0.888), with class-specific AUCs of 0.806 for DLBCL, 0.825 for HT, and 0.756 for MALT lymphoma. Grad-CAM showed that the model focused on lesion-internal echotexture and lesion-transition regions with class-dependent patterns. Conclusions: A deep learning model based on BMUS and CDUS showed promising performance for image-level differentiation of DLBCL, MALT lymphoma and HT in a single-center retrospective cohort. The model outperformed three ultrasound physicians and may serve as a potential decision-support tool. However, the exploratory external validation results should be interpreted as preliminary, and larger multicenter cohorts remain necessary to confirm model generalizability. Full article

An undescribed seco-kaurane diterpenoid, benincaside A (BA), was isolated from the seeds of Benincasa hispida. The seeds of B. hispida have been traditionally used in folk medicine and previous studies have reported anti-tumor potential in B. hispida seed extracts. Accordingly, we investigated the cytotoxicity and underlying mechanisms of BA in colorectal cancer cells. BA inhibited growth in HT29, Colo205, HCT116, and CT26 colorectal cancer cells, as determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while showing no toxicity toward normal human umbilical vein endothelial cells (HUVEC) and human fibroblast WS-1 cells. In HCT116 cells, BA-induced deoxyribonucleic acid (DNA) damage and apoptosis, as evidenced by morphological changes, 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, and assays of caspase-8 and caspase-3 activities. BA triggered apoptotic cell death via the extrinsic pathway, as indicated by elevated caspase-8 and caspase-3 activities. Intracellular reactive oxygen species (ROS) generation was observed in BA-treated HCT116 cells. The growth-inhibitory effects were significantly attenuated by pretreatment with N-acetylcysteine (NAC, an antioxidant), caffeine (an ATM kinase inhibitor), z-VAD-fmk (pan-caspase inhibitor), or z-IETD-fmk (caspase-8-specific inhibitor). Colorimetric assays confirmed increased caspase-8 and caspase-3 activities in BA-treated cells. This study is the first to report ROS-dependent signaling as a key mechanism underlying BA-induced cell death in HCT116 human colorectal cancer cells. Full article

Phosphoric acid-doped polybenzimidazole membranes are a leading fluorine-free electrolyte platform for high-temperature proton exchange membrane fuel cells, enabling proton transport under anhydrous conditions. However, recent evidence shows that conductivity, mechanical stability, and acid retention are intrinsically coupled, preventing independent optimization of these properties. This review establishes a unified framework in which membrane performance is governed by a multidimensional design space defined by acid doping level, activation energy (E_a), hydrogen-bond network topology, and mechanical confinement. Conductivity is shown to scale with both carrier density and hopping energetics, while mechanical stability decays with increasing ADL due to acid-induced plasticization, described through a semi-empirical relationship. Analysis across molecular architectures, including molecular weight control, crosslinking, backbone modification, topological design, and free-volume engineering, demonstrates that performance emerges from a balance between transport efficiency and structural stability. Device-level benchmarking further reveals that similar conductivity values can correspond to orders-of-magnitude differences in voltage decay rate, confirming that durability is governed primarily by mechanical confinement and acid mobility rather than σ alone. A multivariate stability corridor is identified, within which phosphoric acid-doped polybenzimidazole membranes achieve σ ≈ 0.14–0.20 S·cm⁻¹ while maintaining low degradation rates under realistic high temperature proton exchange membrane conditions. Based on this framework, quantitative design rules are derived linking acid doping level, activation, topology, and mechanical properties. This work shifts membrane design from conductivity-driven optimization toward predictive structure–property–durability engineering, providing a basis for the development of next-generation HT-PEM fuel cells with sustained long-term performance. Full article

Neuroimmune interactions in the intestine are essential for maintaining tissue homeostasis, yet they remain poorly understood in teleost fish. This study investigated the structural and cellular organization of enteric neurons and immune cells in the intestine of goldfish (Carassius auratus) using semithin histology, transmission electron microscopy (TEM), and confocal immunofluorescence. Histological observations revealed a well-organized epithelium composed of enterocytes and goblet cells, with numerous lymphocytes located in the basal epithelium. Prominent gut-associated lymphoid tissue (GALT) was identified in both scattered and aggregated forms within the lamina propria and submucosa. Macrophages were widely distributed throughout all intestinal layers and were consistently found in close proximity to enteric neurons and nerve fibers. Ultrastructural analysis confirmed direct contacts between macrophages and neuronal elements. These macrophages exhibited typical phagocytic features, including lysosomes, vacuoles, and engulfed material, particularly in association with myenteric nerve fibers. Immunofluorescence analysis revealed strong expression of toll-like receptor 2 (TLR2) and major histocompatibility complex class II (MHC II) in macrophages and enterocytes, suggesting an active role in antigen recognition. Langerin-positive dendritic-like cells were identified in the submucosa, while CD4-positive lymphocytes showed partial colocalization with serotonin (5-HT). S100-positive cells also exhibited partial overlap with 5-HT, and goblet cells demonstrated serotonin immunoreactivity. In addition, inducible nitric oxide synthase (iNOS) colocalized with TLR2 in submucosal immune cells. These findings demonstrate a close structural and functional association between enteric neurons and immune cells, highlighting an integrated neuroimmune network in the goldfish intestine. Full article

Two new anthraquinone derivatives, (±)-1′-O-methyl-6-chloroaverantin (1a and 1b) and 6-chloroaverythrin (2), and one new diphenyl ether 1-((E)-but-2-en-2-yl)-3,8-dihydroxy-6-((E)-4-hydroxybut-2-en-2-yl)-4,9-dimethyl-11H-dibenzo[b,e][1,4]dioxepin-11-one (3), along with six known compounds, were isolated from the fungus Aspergillus sp. SCSIO 41331 collected from the deep-sea sediment in the cold-seep area of the South China Sea. Elucidation of planar structures was achieved via 1D and 2D NMR and mass spectrometry, whereas stereochemistry was validated through optical rotation and NOE correlations, chiral phase HPLC analysis and NMR calculation. All compounds were assessed for antitumor activity, among which compound 4 displayed moderate antiproliferative activity against HT29 cells and suppressed colony expansion. Full article

Colorectal cancer (CRC) is the third most common malignancy worldwide. Detailed characterization of cell surface proteins (CSPs) is essential for the identification of prognostic biomarkers and the development of novel therapeutic strategies. Cancer progression and epithelial cell polarity influence the expression levels and subcellular localization of these proteins. However, quantitative information on the distribution of CSPs between the apical and basolateral membranes remains limited, particularly in CRC cells. Here, we developed a rapid, high-throughput method based on the enrichment of biotinylated peptides and proteins from the apical and basolateral surfaces of polarized CRC epithelial cells (HT29 and HCT116), followed by LC-MS/MS analysis. This approach enables the simultaneous identification of the side-specific distribution of ~1200 CSPs. In addition, almost 500 potential N-glycosylation sites with the canonical consensus sequence of these proteins were identified, which may serve as targets for future site-specific glycosylation analyses. To evaluate the sensitivity of the method, we altered the surface proteome by generating TKS4-knockout cells and identified several surface markers whose expression levels differed significantly from those of wild-type cells. Overall, our findings provide new insights into the role of CSPs in CRC cells and gene-edited models, particularly in the context of TKS4-dependent epithelial-to-mesenchymal transition (EMT)-like phenotypes that model cancer metastasis. Full article

Nineteen monoterpene indole alkaloids, including twelve new ones, were successfully isolated and identified from the stems and leaves of Uncaria hirsuta (Havil.). The planar structures were elucidated by nuclear magnetic resonance (NMR), high-resolution mass (HRMS), and ultraviolet (UV) analyses. The absolute configurations of new compounds were determined using electron circular dichroism calculations in conjunction with NMR calculations. The acetylcholinesterase inhibitory activity of the isolated compounds was evaluated in vitro. In further biological evaluation, the isolated compounds were evaluated for their neuroprotective effects on HT22 neuronal cells. Six compounds demonstrated significant protective activity. Their intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA fluorescent probe, which markedly attenuated glutamate-induced ROS accumulation. The results not only enrich the knowledge on the structural diversity of monoterpene indole alkaloids but also offer substantial evidence for further pharmacological exploration. Full article

Optimizing the extraction of bioactive compounds from Solidago sp. is essential for the development of plant-derived products with therapeutic and nutraceutical potential. Microwave-assisted (MW) and thermal maceration (TM) extraction of S. canadensis aerial parts were comparatively investigated to maximize total flavonoid content (TFC). The obtained extracts were subsequently freeze-dried for storage prior to chemical and biological analyses. Extraction conditions were optimized using a Box–Behnken design. Chemical characterization was performed by FTIR, HPLC-PDA, LC-MS/MS, and GC-MS, enabling detailed profiling of phenolic compounds and terpenoids. Antioxidant capacity was assessed using the DPPH radical scavenging assay, while cytotoxic activity was evaluated against HepG2, HCT-8, and HT-29 tumor cell lines, with HEK-293 cells used as a non-tumorigenic control cell line. Multivariate analysis (PCA) was applied to establish relationships between phytochemical composition and biological responses. Higher TFC values were obtained using MW extraction, whereas TM extracts exhibited greater antioxidant activity. Both extract types induced selective cytotoxic effects against tumor cell lines, while maintaining negligible toxicity toward normal HEK-293 cells. PCA revealed distinct clustering patterns between MW and TM extracts and confirmed a strong association between phenolic composition and bioactivity. The combination of optimized extraction, freeze-drying, and integrated chemical–biological evaluation produced S. canadensis extracts with well-defined phytochemical profiles and biological activity, supporting their potential use in nutraceutical, and pharmaceutical applications. Full article

The aging population highlights the urgency of interventions targeting oxidative stress and neuroinflammation. This study investigated the anti-aging potential of Zhuyeqing Liquor Extract (ZLE) using hydrogen peroxide (H₂O₂)-induced HT-22 cells and D-galactose-induced aging mice model. Results demonstrated that ZLE exhibited free radical scavenging activity, mitigated neuronal oxidative damage, and suppressed pro-inflammatory cytokine expression. Meanwhile, ZLE alleviated age-related physiological deterioration, improved spatial learning and memory ability, and protected hippocampal neurons in aging mice. Mechanistic analysis revealed that ZLE exerted the bioactivity by activating the SIRT1-Nrf2-HO-1 antioxidant pathway while inhibiting the NF-κB inflammatory pathway. This study suggested that ZLE may have potential as a neuroprotective functional food ingredient, providing a scientific basis for its further development. Full article

Solar cell efficiency depends on both photogeneration and charge collection, with the active layer playing a key role in these processes. In organic solar cells (OSCs), where power conversion efficiency (PCE) remains relatively low, understanding the influence of active layer and metal contact thickness on device performance is essential. In this work, we investigate the effect of P3HT:PCBM and Ag thickness on OSC performance by analyzing the evolution of electrical parameters obtained from J-V measurements over five weeks, with particular attention given to resistance-related degradation behavior. The analyzed OSCs had a cell structure composed of Ag/P3HT:PCBM/TiO₂/ITO/glass, and each material was corroborated by XRD and Raman spectroscopy. The thickness of P3HT:PCBM was modulated by varying the number of spin-coated layers from 1 to 3 (ranging from 75 to 160 nm). This variation increases light absorption, as demonstrated by the optical transmittance spectra. However, device degradation became evident after the third week of fabrication, mainly due to an increase in series resistance, which adversely affected the open-circuit voltage (V_OC), fill factor (FF), and overall device efficiency. The best performance was obtained for devices fabricated with two P3HT:PCBM layers and 18 mg of Ag, achieving a maximum PCE of 0.5%. Full article

Green synthesis of nanoparticles using biological extracts has emerged as a sustainable alternative to conventional physicochemical methods, as it provides eco-friendly reducing and stabilizing agents. In this study, silver–copper bimetallic nanoparticles (Ag/Cu-BNPs) were biosynthesized using an aqueous extract of the medicinal mushroom Hericium erinaceus, and their biological properties were evaluated. Three nanoparticle formulations (M1–M3), differing only in the proportion of H. erinaceus extract, were analyzed and selected based on their optical response in UV–Vis spectroscopy. The synthesized nanoparticles were characterized by UV–Vis spectroscopy, FTIR, TEM, and EDS. Antibacterial activity was assessed against Escherichia coli and Staphylococcus aureus using standard methods, while cytotoxicity was evaluated in cancer cell lines (Caco-2, HT-29, A549, MCF-7) and a normal fibroblast line (HDFn). The synthesized Ag/Cu-BNPs were quasi-spherical with an average size of 9.3 ± 3.4 nm, calculated from TEM image analysis of over 900 particles. They exhibited significant antibacterial activity, particularly against S. aureus, and showed dose-dependent cytotoxicity, with Caco-2 cells being the most sensitive. Notably, the nanoparticles displayed greater selectivity toward cancer cells compared to normal fibroblasts, suggesting potential biomedical applications in antimicrobial and antitumor therapies. These results suggest that H. erinaceus extract is an effective biogenic agent for Ag/Cu-BNP synthesis, and that the resulting nanoparticles possess antimicrobial and cytotoxic properties that warrant further investigation for potential biomedical applications. Full article