Search Results (553)

Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis, requiring innovative approaches to evaluate new therapies. Considering the high activity of unsymmetrical bisacridines (UAs) in PC monolayer cultures, we employed multicellular tumor spheroids (MCTS) to assess whether UAs retain pro-apoptotic activity under more physiologically relevant conditions. Ultra-low attachment plates were used to form spheroids from three PC cell lines (Panc-1, MIA PaCa-2, and AsPC-1) with different genotypes and phenotypes. The effects of UA derivatives (C-2028, C-2045, and C-2053) were evaluated using microscopy and flow cytometry (7-AAD for viability and annexin V-FITC/PI for membrane integrity). UAs altered the morphology of the spheroids and reduced their growth. Notably, Panc-1 spheroids exhibited compromised integrity. The increase in 7-AAD⁺ cells confirmed diminished cell viability, and annexin V-FITC assays showed apoptosis as the dominant death pathway. Interestingly, the exact derivative was most active against a given cell line regardless of culture conditions. These results confirm that UAs maintain anticancer activity in 3D cultures and induce apoptosis, with varying efficacy across different cell lines. This underscores the value of diverse cellular models in compound evaluation and supports UAs as promising candidates for pancreatic cancer therapy. Full article

This study investigates the evolving pedagogical strategies and professional identity development of two novice college English teachers in China through a semester-long classroom-based inquiry. Drawing on Norris’s Multimodal (Inter)action Analysis (MIA), it analyzes 270 min of video-recorded lessons across three instructional stages, supported by visual transcripts and pitch-intensity spectrograms. The analysis reveals each teacher’s transformation from textbook-reliant instruction to student-centered pedagogy, facilitated by multimodal strategies such as gaze, vocal pitch, gesture, and head movement. These shifts unfold across the following three evolving identity configurations: compliance, experimentation, and dialogic enactment. Rather than following a linear path, identity development is shown as a negotiated process shaped by institutional demands and classroom interactional realities. By foregrounding the multimodal enactment of self in a non-Western educational context, this study offers insights into how novice EFL teachers navigate tensions between traditional discourse norms and reform-driven pedagogical expectations, contributing to broader understandings of identity formation in global higher education. Full article

Traditional intensive agricultural system impedes ecological functions, such as nutrient cycling and biodiversity conservation, resulting in excessive nitrogen discharge, CH₄ emission, and ecosystem service losses. To enhance critical ecosystem services and mitigate environmental externalities in paddy fields, we developed a multi-objective agricultural system (MIA system), which combines two eco-functional units: paddy wetlands and Beitang (irrigation water collection pond). Pilot study results demonstrated that the MIA system enhanced biodiversity and inhibited pest outbreak, with only a marginal reduction in rice production compared with the control. Additionally, the paddy wetland effectively removed nitrogen, with removal rates of total nitrogen and dissolved inorganic nitrogen ranging from 0.06 to 0.65 g N m⁻² d⁻¹ and from 0.02 to 0.22 g N m⁻² d⁻¹, respectively. Continuous water flow in the paddy wetland reduced the CH₄ emission by 84.4% compared with the static water conditions. Furthermore, a simulation experiment indicated that tide flow was more effective in mitigating CH₄ emission, with a 68.3% reduction compared with the drying–wetting cycle treatment. The emergy evaluation demonstrated that the MIA system outperformed the ordinary paddy field when considering both critical ecosystem services and environmental externalities. The MIA system exhibited higher emergy self-sufficiency ratio, emergy yield ratio, and emergy sustainable index, along with a lower environmental load ratio. Additionally, the system required minimal transformation, thus a modest investment. By presenting the case of the MIA system, we provide a theoretical foundation for comprehensive management and assessment of agricultural ecosystems, highlighting its significant potential for widespread application. Full article

Pancreatic cancer is among the deadliest malignancies, with limited treatment options and poor prognosis. Novel strategies are therefore urgently needed. Sotorasib, a KRAS G12C-specific inhibitor, offers targeted treatment for a small subset of patients with this mutation. Electrochemotherapy (ECT), which enhances the cytotoxicity of chemotherapeutic agents through electroporation-induced membrane permeabilization, has shown promise in various tumor types, including deep-seated malignancies such as pancreatic cancer. Combining ECT with sotorasib may potentiate antitumor effects in KRAS G12C-mutated pancreatic cancer; however, preclinical data on such combinations are lacking. This proof-of-concept study evaluated the cytotoxic effects of ECT using bleomycin (BLM) or cisplatin (CDDP) in combination with sotorasib in KRAS G12C-mutated MIA PaCa-2 and KRAS G12D-mutated PANC-1 pancreatic cancer cell lines. ECT alone significantly reduced cell viability, particularly in MIA PaCa-2 cells, where electric pulses induced approximately 75% cell death. Combining ECT with sotorasib resulted in an additive effect on KRAS G12C-mutated MIA PaCa-2 cells, though no synergy was observed, likely due to the high intrinsic sensitivity to electric pulses. These results support the potential of combining physical and molecular therapies in a subset of pancreatic cancer patients and lay the groundwork for further in vivo studies to optimize treatment parameters and explore clinical translatability. Full article

Background/Objectives: This paper presents a medical image analysis application designed to facilitate advanced edge detection and fuzzy processing techniques within an intuitive, modular graphical user interface. Methods: Key functionalities include classical edge detection, Ant Colony Optimization (ACO)-based edge extraction, and fuzzy edge generation, which offer improved boundary representation in images where uncertainty and soft transitions are prevalent. Results: One of the main novelties in contrast to the initial innovative Medical Image Analyzer, iMIA, is the fact that the system includes fuzzy C-means clustering to support tissue classification and unsupervised segmentation based on pixel intensity distribution. The application also features an interactive zooming and panning module with the option to overlay edge detection results. As another novelty, fuzzy performance metrics were added, including fuzzy false negatives, fuzzy false positives, fuzzy true positives, and the fuzzy index, offering a more comprehensive and uncertainty-aware evaluation of edge detection accuracy. Conclusions: The application executable file is provided at no cost for the purposes of evaluation and testing. Full article

A novel ruthenium(II) complex, [RuCl₂(η⁶-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex 1 with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol⁻¹. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of 1 as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors. Full article

Background: The suitability of minimally invasive adrenalectomy (MIA) for adrenal tumors ≥6 cm remains debated due to technical challenges and oncological concerns. This study aimed to assess the safety and feasibility of MIA for large adrenal tumors by comparing surgical outcomes with smaller tumors. Methods: This retrospective cohort study included 269 patients who underwent MIA (2013–2023), divided into two groups: Group A (<6 cm, n = 197) and Group B (≥6 cm, n = 72). The primary endpoint was the postoperative complication rate; secondary endpoints included conversion to open surgery and postoperative length of stay (LOS). Results: Multivariate analysis identified no factors associated with postoperative complications; however, tumor size ≥ 6 cm was associated with conversion to open surgery (p = 0.031). Bilateral procedures and a higher Charlson comorbidity index were associated with longer LOS (p < 0.001 and p = 0.015, respectively). Conclusions: MIA is a safe and feasible approach for tumors ≥6 cm, despite being associated with a higher conversion rate. Full article

Osteoarthritis (OA) is a progressive joint disease that is commonly managed with palliative drugs, many of which are associated with undesirable side effects. This study investigated the therapeutic potential of a novel supplementation with guarana, selenium, and L-carnitine (GSC) in a rat model of chemically induced OA. Forty male Wistar rats (8–9 weeks old) received intra-articular sodium monoiodoacetate (Mia) to induce OA, and were subsequently treated with GSC. Inflammatory and oxidative stress parameters were analyzed at the end of the experiment. GSC supplementation enhanced endogenous antioxidant defenses, suggesting systemic antioxidant activity. However, no histological improvement was observed. In silico analyses indicated that Mia-induced OA may involve a complex molecular environment that GSC, at the tested dose, failed to modulate at the site of injury. Despite the limited local effects, these findings support the systemic benefits of GSC and highlight the potential of natural compound-based strategies in OA management. Given the adverse effects of conventional pharmacotherapy, the development of alternative, naturally derived treatments remains a promising avenue for future research. Full article

Monoterpene indole alkaloids (MIAs) exhibit diverse structures and pharmacological effects. Annotating MIAs in herbal medicines remains challenging when using liquid chromatography combined with high-resolution mass spectrometry (LC-HRMS). This study introduced a new annotation strategy employing LC-HRMS to efficiently identify MIAs in herbal medicines. Briefly, MS² spectra under multiple collision energies (MCEs/MS²) helped capture high-quality product ions across a range of mass-to-charge (m/z) values, revealing key MS² features such as diagnostic product ions (DPIs), characteristic cleavages (CCs), and neutral/radical losses (NLs/RLs). Next, feature-based molecular networking (FBMN) was created to map the structural relationships among MIAs across large MS datasets. Potential MIAs were then graded and annotated through systematic comparison with known biosynthetic pathways (BPs), derived skeletons, and their characteristic substituents. The MCEs/MS²-FBMN/BPs workflow was first applied to annotate MIAs in the alkaloids from the leaf of Alstonia scholaris (ALAS), a new botanical drug for respiratory diseases. A total of 229 MIAs were systematically annotated and classified, forming a solid basis for future clinical research on ALAS. This study offers an effective strategy that enhances the structural annotation of MIAs within complex herbal medicines. Full article

Background: The progressive course of coronavirus disease 2019 (COVID-19) is more frequently observed in individuals with obesity, diabetes, pulmonary and cardiovascular disease, or arterial hypertension. Many patients with these conditions are prescribed statins to treat hypercholesterolaemia. However, statins exhibit additional pleiotropic effects. The present study aims to investigate the effects of all eight currently existing statins on the expression of genes whose products have been reported to be directly associated with complicated COVID-19 disease. Methods: We extended the interpretation of the whole-genome DNA microarray analyses of pancreatic cancer cells MiaPaCa-2 and whole-transcriptome analyses of adipose tissue-derived mesenchymal stem cells AD-MSC that we had performed in the past. From the number of genes with altered expression induced by statins, we focused on those reported to be involved in a complicated course of COVID-19, including APOE and ACE2, genes encoding proteins involved in innate antiviral immunity and respiratory failure genes. Results: Although we did not observe statin-induced changes in the expression of APOE, ACE2 and any of the six genes clustered in the locus associated with respiratory failure in patients with COVID-19, some statins induced changes in the expression of genes encoding their interaction partners. Among genes associated with the immune system, all statins, which are effective in vitro affected the expression of genes encoding IL-6 and IL-8 and interaction partners of NF-kB, which may influence the duration of viral persistence. Conclusions: Statins act on multiple pathways simultaneously, some of which support COVID-19 development, while others suppress it. Full article

Background/Objectives: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aimed to enhance the potency and scalability of DC-based immunotherapy by developing an allogeneic DC platform derived from CD34⁺ hematopoietic stem cells (HSCs), genetically engineered to overexpress CD93, CD40L, and CXCL13, followed by maturation and tumor antigen pulsing. Methods: Engineered DCs were generated from CD34⁺ HSCs and matured in vitro after lentiviral transduction of CD93, CD40L, and CXCL13. Tumor lysates were used for antigen pulsing. A scrambled-sequence control DC was used for comparison. In vitro assays were performed to assess T cell activation and tumor cell killing. In vivo efficacy was evaluated using orthotopic pancreatic tumors in BLT and PBMC-humanized NSG mice established with the MiaPaca-2 (MP2) cell line. Results: Engineered DCs significantly enhanced T cell activation and tumor-specific cytotoxicity in vitro compared to control DCs. Antigen pulsing further amplified immune activation. In vivo, treated humanized mice showed increased CD4⁺, CD8⁺, and NK cell frequencies in peripheral blood and within tumors, correlating with reduced tumor burden. Conclusions: Our data shows that the antigen-pulsed, engineered DCs have the potency to activate immune cells, which leads to a significant reduction in pancreatic tumors and therefore could potentially provide an effective therapeutic opportunity for the treatment of pancreatic cancer and other solid tumors. Full article

Background/Objectives: Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms remains a critical neurosurgical emergency with high morbidity and mortality. The presence of multiple intracranial aneurysms (MIAs) in SAH patients presents a therapeutic challenge, particularly in choosing between single-stage and multiple-stage interventions. In patients with aneurysmal SAH and multiple intracranial aneurysms, we compared single-stage vs. multiple-stage interventions regarding vasospasm occurrence, complication rates, and short-term neurological outcomes in a retrospective cohort. Methods: This retrospective cohort study included 44 patients diagnosed with aneurysmal SAH and at least one additional unruptured aneurysm. Patients were categorized based on the intervention strategy. A “single-stage” intervention was defined as treatment of both the ruptured and all unruptured aneurysms in the same operative session. A “multiple-stage” intervention referred to a planned approach in which additional aneurysms were treated in separate, subsequent procedures. Clinical severity was assessed using scores. Aneurysm characteristics and treatment modalities were recorded. Outcomes were analyzed and compared between intervention groups. Statistical analysis was performed, with p < 0.05 considered significant. Results: The cohort included 44 patients with a total of 109 aneurysms. Most patients were female (68.2%), with a mean age of 54.5 years. The majority of aneurysms were small- to medium-sized and commonly located in the anterior circulation. Among the patients, 19.0% underwent single-stage interventions, and 28.6% underwent multiple-stage procedures. Vasospasm occurred significantly more often in the single-stage group (83.9% vs. 46.2%, p = 0.028). No significant difference was found in hospital stay duration between groups. The MRS scores showed a trend toward worse outcomes in the single-stage group (p = 0.060), as did the rates of post-operative neurological deficits (p = 0.079). Conclusions: In patients with SAH and MIAs, single-stage interventions may increase vasospasm risk. Although they offer logistical benefits, outcomes should be interpreted with caution given baseline differences and limited statistical adjustment. Full article

We propose a trustworthy load prediction method for a cantilever roadheader robot without imputation. Specifically, we design a load-trustworthy-boosting (LTB) algorithm for coal and rock cutting loads that accounts for missing data in complex underground environments. We introduce a trustworthy decision tree that integrates mixed-integer programming (MIP) and Missing Incorporated in Attributes (MIA) as the base predictor, which can handle missing data, thereby accelerating load prediction and improving prediction accuracy. Furthermore, we utilize boosting techniques to enhance the prediction performance of the base predictor by incorporating cutting safety–trust constraints during the prediction process. We derive the convergence of the algorithm theoretically and verify the accuracy and reliability of the algorithm through experiments. The experimental results show that the proposed algorithm is superior to state-of-the-art load prediction algorithms both without and with missing data considered. This method can provide a reliable decision-making basis for underground unmanned intelligent excavation. Full article

Background/Objectives: Osteoarthritis is a degenerative joint disease that affects people worldwide. It is characterized by joint pain, synovial inflammation, and the degradation of articular cartilage with subchondral bone. Presently, there is no known cure, and pharmacological treatment options are limited. Blueberries contain phytochemicals, which have been linked to positive health benefits and may offer therapeutic benefits. Therefore, the purpose of this study was to examine the dose-dependent effects of whole blueberries on arthritis symptoms in a monosodium iodoacetate (MIA)-induced rat model of osteoarthritis. Methods: Forty female rats were used for this study. Thirty were injected with MIA to induce joint degradation associated with osteoarthritis. Ten served as controls without MIA induction. The MIA-induced rats were randomized into three groups. All groups were fed a casein-based diet, with two of the MIA-induced groups receiving an addition of whole-blueberry powder at 5% and 10%. Fasted blood specimens and tissues of interest were collected post-euthanasia for analysis. Mechanical allodynia and joint widths were assessed throughout this study. Results: MIA induction resulted in changes in pain behaviors and the development of mechanical allodynia. The MIA injection produced inflammation, pain symptoms, and behaviors that are representative of those observed in humans with osteoarthritis. The incorporation of whole blueberries into diets reduced pain behaviors and inflammation. Conclusions: Overall, whole blueberries showed limited, non-dose-dependent effects in the MIA-induced rat model of osteoarthritis. While some outcomes improved in blueberry-treated groups, the overall results were not consistently significant. These preliminary findings suggest potential biological activity and support the further investigation of blueberries’ therapeutic efficacy. Full article

MiaA is responsible for the addition of the isopentyl modification to adenine 37 in the anticodon stem loop of specific tRNAs in Escherichia coli. Mutants in miaA have pleotropic effects on the cell in E. coli and play a role in virulence gene regulation. In addition, MiaA is necessary for stress response gene expression by promoting efficient decoding of UUX-leucine codons, and genes with elevated UUX-leucine codons may be a regulatory target for i⁶A-modified tRNAs. Understanding the temporal nature of the i⁶A modification status of tRNAs would help us determine the regulatory potential of MiaA and its potential interplay with leucine codon frequency. In this work, we set out to uncover additional information about the synthesis of the MiaA. MiaA synthesis is primarily driven at the transcriptional level from multiple promoters in a complex operon. However, very little is known about the post-transcriptional regulation of MiaA, including the role of sRNAs in its synthesis. To determine the role of small RNAs (sRNAs) in the regulation of miaA, we constructed a chromosomal miaA-lacZ translational fusion driven by the arabinose-responsive P_BAD promoter and used it to screen against an Escherichia coli sRNA library (containing sRNAs driven by the IPTG-inducible P_Lac promoter). Our genetic screen and quantitative β-galactosidase assays identified CsrB and its cognate protein CsrA as potential regulators of miaA expression in E. coli. Consistent with our hypothesis that CsrA regulates miaA post-transcriptional gene expression through binding to the miaA mRNA 5′ UTR, and CsrB binds and regulates miaA post-transcriptional gene expression through sequestration of CsrA levels, a deletion of csrA significantly reduced expression of the reporter fusion as well as reducing miaA mRNA levels. These results suggest that under conditions where CsrA is inhibited, miaA mRNA translation and thus MiaA-dependent tRNA modification may be limited. Full article