Browse Articles

Cytotoxic activity of marine derived bioactive compounds from red sea sponges supported by LC-MS/MS profiling and molecular docking

Abstract Marine sponges are prolific sources of structurally diverse secondary metabolites with notable pharmacological potential. This study aimed to explore and compare the chemical composition and cytotoxic activity against liver cancer cells of three Red Sea sponge species— Stylissa carteri , Hemimycale arabica , and Negombata magnifica —collected from distinct ecological sites. Sequential solvent extraction was conducted using n-hexane, ethyl acetate, and n-butanol, followed by phytochemical screening, and LC–MS/MS-based metabolite profiling. Cytotoxicity was evaluated through MTT assay, colony formation, and wound healing (scratch) assay against HepG2 liver cancer cells. Molecular docking was carried out using the Chk2 kinase receptor to assess binding affinities and interaction modes of the identified metabolites. The total MeOH:DCM extract of S. carteri (El Gouna) showed potent cytotoxicity, with an IC 50 of 37 µg/mL, 80% growth inhibition in the MTT assay, and significant suppression of colony formation (20.3 ± 2.1% survival) and cell migration (35.4 ± 2.1% wound closure). LC–MS/MS analysis tentatively identified pyrrole–imidazole alkaloids, including hymenialdisine, oroidin, and spongiacidin D. Docking revealed strong binding affinities of hymenialdisine (− 8.35 kcal/mol) and spongiacidin D (− 7.30 kcal/mol) with key Chk2 active-site residues. MD simulations indicated that the hymenialdisine–Chk2 complex maintained stability throughout 100 ns, with reduced RMSD (2.54 ± 0.48 Å), RMSF (1.46 ± 0.14 Å), Rg (20.70 ± 0.17 Å), and SASA (13,916 Å 2 ) compared to the Apo protein, confirming a rigid and stable ligand–protein interaction. MM/GBSA calculations revealed a favorable total binding free energy (ΔG_bind =  − 33.17 ± 0.17 kcal/mol), dominated by van der Waals and electrostatic contributions. ADMET predictions indicated compliance with Lipinski and Veber rules, suggesting good oral bioavailability. S. carteri from El Gouna is enriched in bioactive brominated alkaloids that exhibit potent cytotoxic activity against HepG2 cells. Integration of cytotoxic assays, LC–MS/MS profiling, docking, and MD simulations underscores the influence of species and environmental conditions on sponge-derived bioactivity. These findings provide a strong rationale for advancing S. carteri metabolites, especially hymenialdisine and spongiacidin D as potential cytotoxic agents.

Determination of the temporal-spatial pattern distribution and evolution of industrial heritage in Northeast China and its influencing factors

Foot-and-mouth disease virus-derived dendrimer peptides induce germinal center-dependent antibody responses and IgG1 plasma cell differentiation in mice

Abstract Our previous findings demonstrated that the B 2 T dendrimer peptide, harboring B- and T-cell foot-and-mouth disease virus (FMDV) epitopes, confers protection in swine and elicits in mice significant levels of neutralizing antibodies, a key correlate of protection against FMDV. Here, we use a mouse model to study the germinal center (GC) B-cell response in B 2 T-immunized mice, as this peptide is aimed to enhance antigen-specific immune responses, relying on T-cell help to potentiate B-cell activation and maturation. Flow cytometry revealed that immunization with B 2 T enhanced GC formation and increased the proportion of IgG1-positive GC B-cells in draining lymph nodes. Additionally, elevated levels of IgG1-secreting B-cells in bone marrow are consistent with the initiation of GC–derived plasma cell differentiation, highlighting B 2 T’s ability to potentiate antigen-specific immunity through coordinated B- and T-cell activation. The study demonstrated that only B 2 T, but not the version lacking T-cell epitope (B 2 ), triggered neutralizing antibody production and a robust T-cell response in the spleen, underscoring the critical role of CD4 + T-cell help mediated by the T-cell epitope in eliciting protective immunity. Even though these studies need to be extended to natural hosts such as swine, our results highlight the role of the B 2 T dendrimer in inducing IgG1-secreting long-lived plasma cells in the bone marrow, providing insights into the mechanisms underlying the durable immunity elicited by epitope-linked dendrimer vaccines.

Climate shocks, not just warming, threaten malaria control efforts in Africa

Analysis of the correlation between lower limb muscle synergy characteristics and landing load during single-leg landing in humans

High-throughput sequencing-based virome analysis reveals genomic diversity and recombination of tomato-infecting viruses in Korea

Global and regional evaluation of Corythucha marmorata distribution under different spatial modeling conditions

Research on establishment of bonded particle model for pellet feed and its application

Abstract This study develops and validates a bonded particle model to investigate impact-induced breakage of piglet pellet feed using the discrete element method. To address the lack of reliable DEM parameters for pellet attrition, bonding properties were calibrated through uniaxial compression experiments combined with numerical simulations and response surface optimization. The calibrated parameters include a normal stiffness per unit area of 2.00e10 N/m 3 , a tangential stiffness per unit area of 7.41e9 N/m 3 , and bond strengths of 500 MPa. The validated model was applied to simulate pellet motion and fragmentation in a centrifugal impact device. The breakage rate increased monotonically with impeller speed from 500 to 1500 rpm, reaching 21.43% at the highest speed, in good agreement with experimental results. A strong linear correlation (R 2  = 0.9970) between simulated bond breakage fraction and experimentally measured mass-based breakage rate confirms that bond failure percentage provides a physically meaningful descriptor of macroscopic fragmentation. In addition, breakage exhibited a non-linear dependence on impact angle, with a maximum value of 6.86% at 75° due to the combined axial and radial loading effects. The proposed framework can provide theoretical guidance for improving pellet durability and optimizing processing conditions.

See raining iguanas and coral from the inside out — February’s best science images

Pooled analyses of Clostridioides difficile vaccine trials identify baseline predictors for vaccine response

Abstract Clostridioides difficile ( C. difficile ) is a major cause of severe diarrhea and colitis usually affecting individuals with dysbiosis. Currently, there is no licensed vaccine nor prophylaxis for C. difficile infection (CDI), while treatment remains challenging. To support immunogenicity assessment and vaccine development programs, we analyzed data from two Sanofi vaccine trials (Phase II and III) with 1,096 participants. We evaluated baseline predictors of 16 seroresponse outcomes, measured 30 days after the third vaccine dose, using five statistical models. Relevant predictors of positive seroresponse after vaccination for both Toxin A and B included lower comorbidity index, age < 65 years, and future CDI risk exposure (i.e., impending hospitalization/nursing facility admission were more relevant than past-exposure history). Higher baseline antibody levels, North American study region, and female sex were mainly related with Toxin B seroresponse. These findings highlight the need for further research to optimize vaccine trial design and personalized vaccination approaches.

Dynamic hand exercise recognition for game-based finger rehabilitation

Abstract Frequent and intense exercise is crucial for rehabilitation, but motivation is often a barrier. Recent studies indicate that exergames can enhance motivation and exercise intensity by using targeted motor function for game control. Generally, one way to achieve this is to enable the control of such games by the targeted motor function. For example, in finger rehabilitation, selected exercises control exergames, relying on both representative hand gestures and accurate recognition systems. However, existing recognition systems in the literature are modeled based on hand gesture datasets that are not representative of common finger rehabilitation exercises. Therefore, this work deviates from the pull of previous works by developing a hand-gesture recognition system using a dataset collected specifically for the purpose of finger rehabilitation. The dataset comprises RGB images collected from 14 different subjects while performing 7 different finger exercises under varying backgrounds and lighting conditions. A learning network that leverages transfer learning of an off-the-shelf pre-trained VGG16 model using both feature extraction and fine-tuning is developed to recognize the seven different hand gestures featured in the dataset. The resulting models achieved an accuracy of 82.38% and 85.12% before and after fine-tuning respectively. Furthermore, the misclassification rate observed for specific classes was analyzed using the class activation map. The resulting model is integrated into an exergame framework and an experimental study conducted with 15 unimpaired participants demonstrates the suitability of the framework for game-based finger rehabilitation through user-experience measures such as Intrinsic Motivation Inventory (IMI), flow experience, and overall gaming experience.

Hey ChatGPT, write me a fictional paper: these LLMs are willing to commit academic fraud

Compound effects of dams and levees reshape Yangtze flood dynamics and reveal substantial risk misestimations from ignoring levees

Quantum-Inspired Adaptive Meta-Heuristic–Machine Learning framework for resilient and energy-efficient task scheduling in multi-cloud ecosystems

Clearing trapped cholesterol could relieve lymphoedema

Targeted deletion of c-kit in TECs attenuates UUO-induced renal fibrosis through NF-κB pathway inhibition

Abstract Renal interstitial fibrosis (RIF) is the cardinal pathological hallmark of chronic kidney disease (CKD). Although the stem-cell factor (SCF)/c-kit axis has been implicated in kidney fibrogenesis, its cell-specific role and downstream mechanism in tubular epithelial cells (TECs) remain undefined. We investigated whether TEC-derived SCF/c-kit signaling propels RIF after unilateral ureteral obstruction (UUO) via Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) activation. Using the Cre-loxP system, a renal tubular epithelial cell-specific c-kit gene knockout mouse model (Ggt1-Cre c-kit −/− ) was established. Renal interstitial fibrosis was induced in both C57BL/6J (WT) and Ggt1-Cre c-kit −/− mice via UUO surgery. The extent of fibrosis was evaluated by assessing renal function indicators (serum creatinine and blood urea nitrogen), renal histopathology (PAS and Sirius red staining), and the expression of fibrosis markers (α-SMA, Vimentin, and Collagen I). Western blot and immunofluorescence techniques were employed to detect the expression of fibrosis markers, key proteins of the NF-κB pathway (p-p65, p65, p-IκBα, and IκBα), and inflammatory cytokines (Interleukin (IL)-6 and IL-1β). Primary renal tubular epithelial cells were isolated and cultured ex vivo, and treated with SCF and the NF-κB-specific inhibitor SC-75741 to evaluate the degree of cellular fibrosis and the activation status of the NF-κB pathway. Fourteen days after UUO, renal SCF and c-kit expression paralleled the rise in fibrotic markers. TEC‑specific deletion of c‑kit ameliorates the initial decline in renal function, attenuates tubular injury, reduces collagen deposition, and downregulates the expression of fibrotic proteins. Genetic deletion of c-kit significantly inhibits NF-κB phosphorylation and the expression of inflammatory cytokines IL-6 and IL-1β. In vitro, SCF provoked a fibrogenic phenotype in WT TECs that was abolished by either c-kit deletion or SC-75741. The SCF/c-kit signaling pathway in TECs promotes renal interstitial fibrosis in UUO mice via activation of the NF-κB pathway. Targeted inhibition of c-kit in TECs alleviates inflammatory responses and fibrosis, improves renal function, and may offer a novel therapeutic target for delaying the progression of CKD.

Jam-packed star system is most compact of its kind ever found

Study on treatment of oil extraction wastewater by grounding electrode atomization corona discharge coupling flocculant

AI caption generation model for digital pathology of adenocarcinoma in endoscopic histopathology using multi-instance attention mechanisms

Levels and instability of transthyretin and correlations with core biomarkers in Alzheimer’s disease

Abstract Transthyretin (TTR) has gained attention due to its implication in Alzheimer’s Disease (AD) by modulating amyloid-beta (Aβ) pathology. This study aimed to establish associations between TTR and key AD biomarkers, to enhance our understanding of the role of TTR in AD pathogenesis. We evaluated TTR levels and tetrameric instability in plasma and CSF in mild cognitive impairment (MCI-AD) and Dementia-AD patients examining associations with clinical, biochemical and genetic data. Plasma TTR levels were lower in Dementia-AD, especially in women. In the MCI-AD group, CSF TTR levels inversely correlated with markers of amyloid pathology and neurodegeneration such as Aβ40, p-Tau181, t-Tau and NfL. CSF TTR instability was negatively associated with CSF Aβ42, indicating an association with increased amyloid burden. In the whole cohort, plasma TTR instability correlated with CSF TTR instability. In line with the strong association between CSF TTR instability and Aβ42, we showed increased TTR instability in samples incubated with Aβ42. No significant associations were observed in the Dementia-AD group. This study emphasizes that TTR is associated with Aβ clearance and neurodegeneration. We propose Aβ42 and its increase in the brain as a factor destabilizing the TTR tetrameric fold, impairing TTR function.