Search Results (669)

The development of sustainable technologies capable of simultaneously addressing environmental pollution and renewable energy production remains a major scientific challenge. In this work, titanium dioxide nanoparticles (GTiO₂) were synthesized through a plant-extract-assisted route using Punica granatum (pomegranate) peel extract and subsequently modified with platinum nanoparticles (Pt NPs) to obtain an efficient photocatalyst for the photoreforming of organic pollutants. The resulting Pt-GTiO₂ material exhibited an anatase crystal structure with an average crystallite size of approximately 12 nm and a specific surface area of about 140 m² g⁻¹. Comprehensive characterization using XRD, BET, TEM, FTIR, Raman, and photoluminescence spectroscopy (PL) revealed favorable structural and optoelectronic properties that promote efficient charge separation. The photocatalytic performance of Pt-GTiO₂ was evaluated through the simultaneous degradation of 2-naphthol, a priority aromatic pollutant, and hydrogen evolution under simulated solar irradiation in anaerobic conditions. Under the investigated conditions, Pt-GTiO₂ effectively promoted 2-naphthol degradation, with substantial but incomplete mineralization, as confirmed by TOC removal. The synthesized catalyst showed degradation efficiency higher than Pt-UV100 and comparable to Pt-P25, while exhibiting superior hydrogen evolution when compared with Pt-P25. Mechanistic investigations combining scavenger experiments, electron paramagnetic resonance (EPR) spectroscopy, and the identification of reaction intermediates suggest that photogenerated holes play a major role in the initial oxidation step under the mechanistic test conditions. The detected intermediates indicate that photoreforming proceeds via multiple pathways, including hydroxylation, ring-opening, reduction, and fragmentation. These findings highlight the potential of biogenic TiO₂-based photocatalysts for converting hazardous organic pollutants into clean hydrogen fuel while simultaneously achieving wastewater purification, offering a promising route toward sustainable environmental and energy technologies. Full article

Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia–reperfusion (RIR) injury, and Alzheimer’s disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood–retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-β–driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), Müller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders. Full article

The new projective solutions methods (PSMs) for solving the Stokes, Oseen, and Brinkman flow problems are presented in this paper. They automatically satisfy the governing equations and are therefore Trefftz-type methods. Utilizing the third-order formulation and three-dimensional analytic functions, we derive a meshless Trefftz-type method to solve three-dimensional Stokes flow problems. The Oseen and Brinkman equations are transformed into four coupled third-order/first-order partial differential equations. The projective-type particular solution (PTPS) is obtained via a projective function in terms of the projective variable; the third-order ordinary differential equations (ODEs) with constant coefficients are derived to determine the projective functions. The Trefftz-type PSM is extremely accurate, because the governing equations (including the incompressibility condition) are implemented automatically. For the Brinkman equations, the general solutions of velocity and pressure are presented by using the Helmholtz function and a harmonic function, whose corresponding Trefftz-type numerical method is developed. Upon comparison with the method of fundamental solutions (MFS), the new methods exhibit some advantages, including lower condition numbers, faster convergence, and better accuracy. We also apply the Trefftz-type PSM to solve the exterior problem of the Stokes equations, where the velocity tends to zero at infinity. Full article

Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited efficacy over time, and high costs. Consequently, there is growing interest in alternative therapies, especially those derived from traditional medicinal plants, that have long been employed in various cultures for managing diabetes. Recent advances in phytochemistry have identified bioactive plant secondary metabolites with promising antidiabetic properties. This review aims to provide a comprehensive overview of plant-derived compounds that exhibit inhibitory activity against key diabetes-related enzymes, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-4 (DPP-4). These enzymes play critical roles in glucose metabolism and insulin signaling pathways. The review highlights the structural diversity of these natural inhibitors, their mechanisms of action, and their effectiveness in preclinical models. Understanding the molecular interactions and pharmacological profiles of these metabolites may facilitate the development of safer and more effective antidiabetic agents. Full article

Background: Leukemic non-nodal variant mantle cell lymphoma (nnMCL) is an uncommon subtype of mantle cell lymphoma that lacks lymphadenopathy and generally follows an indolent clinical course. Adverse genetic alterations such as TP53 inactivation and del(13q) may have prognostic significance. Clinical findings such as splenomegaly may serve as a clue to the diagnosis and should prompt further evaluation. Case Presentation: We describe a 91-year-old woman who presented with a one-month history of anemia (hemoglobin 12.3 g/dL), mild thrombocytopenia (platelets 136 × 10⁹/L), isolated splenomegaly and no palpable lymphadenopathy. Despite a normal total white blood cell count, intermittent relative lymphocytosis with atypical lymphocytes (4%) and smudge cells was detected on the complete blood count. Peripheral blood flow cytometry demonstrated a monoclonal kappa-restricted B-cell population negative for CD5 and CD10, comprising approximately 20% of lymphocytes. Conventional karyotyping and fluorescent in situ hybridization (FISH) analysis identified del(13q), del(17p)/TP53, and IGH-CCND1 rearrangement in 8–19.5% of peripheral blood leukocytes. A month after the initial assessment, the patient presented following a fall. CT imaging of the abdomen revealed marked splenomegaly, a large subcapsular/perisplenic hematoma, and moderate-to-large hemoperitoneum. Emergent laparotomy showed an enlarged spleen (1490 g, 23 × 16 × 7.5 cm) with laceration. Histologic evaluation showed atypical lymphoid cells positive for CD20 and cyclin D1, with strong p53 expression, negative for CD5 and SOX11, and a low Ki-67 index. Similar involvement was identified in the small bowel and appendix. Targeted sequencing of splenic tissue, performed as part of a retrospective molecular characterization, identified a pathogenic TP53 variant (p.His179Gln). Conclusions: This case provides a rare opportunity to evaluate splenic and small intestinal involvement by nnMCL at both the gross and histologic levels. It highlights the importance of integrating clinical findings with flow cytometry, imaging, cytogenetic, and molecular data in establishing the diagnosis. Even when peripheral blood findings suggest a low disease burden, imaging may better define the extent of disease and support appropriate clinical assessment, particularly in elderly patients at risk for complications related to splenomegaly. Full article

Background: The pathophysiological mechanisms of Moyamoya angiopathy (MA) are still largely unknown, although a dysfunctional vasculogenesis has been hypothesized to contribute to it. The association between this rare cerebrovascular condition and variants of Ring Finger Protein 213 (RNF213) strengthens the role of genetic factors in MA pathogenesis. Methods: To investigate the molecular mechanisms of MA, we carried out RNA interference (RNAi) targeting RNF213 in human endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). The combined effect of RNAi and/or hypoxia on expression of key angiogenic factors was analyzed through qRT-PCR and Western blot. Functional assays were performed to characterize the impact of RNAi on vasculogenesis. Gene-expression arrays were performed on vessel walls of MA patients and controls. Results: RNF213-RNAi impaired angiogenic capability in ECs, whereas the simultaneous silencing of RNF213 and its phosphatase PTP1B restored angiogenesis function in ECs but worsened it in VSMCs. Angiogenic factor expression appeared to be modulated in ECs by the combined effects of RNAi and/or hypoxia, and in pathological vessels of MA patients as compared with controls. Conclusions: Our findings contribute to associating the relevance of RNF213 in MA cellular models and highlight the importance of EC-VSMC crosstalk for vascular integrity. Additionally, the study could lay the foundations for improving experimental models of MA pathophysiology. Full article

The increasing digitalization of electrical substations, enabled by IEC 61850-based architectures, has improved operational efficiency while expanding the cyber attack surface. This paper introduces a standards-aligned cybersecurity risk mitigation model specifically designed for digital substations and mapped to representative attack scenarios. The model integrates preventive, detective, and application-level controls derived from NIST SP 800-82r3, IEC 62443, and ISO/IEC 27019, and is validated in a laboratory process-bus environment. A baseline risk assessment identified four high-risk scenarios in the studied digital substation architecture. For validation, a selected subset of controls was experimentally evaluated against two representative attack vectors, namely false data injection (FDI) on GOOSE messages and denial-of-service (DoS) against PTP synchronization. For the remaining scenarios, the post-mitigation effects were reassessed analytically based on control coverage, architectural exposure, and standards-aligned cybersecurity reasoning. The experimental validation demonstrated that both empirically tested high-risk scenarios (FDI on GOOSE and DoS on PTP) were effectively mitigated, reducing their residual risk to moderate and low levels, respectively. For the remaining two scenarios, a post-mitigation analytical reassessment based on control coverage and architectural exposure suggested a consistent risk reduction trend, although without direct experimental confirmation. Under this combined empirical–analytical assessment, the number of high-risk scenarios decreased from four to one, corresponding to a 50% experimentally validated reduction in high-risk exposure, complemented by an analytical reassessment of the remaining scenarios. These results provide quantitative evidence about the effectiveness of the model, even with partial implementation. The scientific contribution of this study lies in integrating multistandard cybersecurity requirements into an operational mitigation model tailored to IEC 61850 substations, combined with experimental risk quantification in a realistic process-bus testbed. The proposed model offers practical guidance for utilities and establishes a scalable foundation for advancing cybersecurity in critical power infrastructure. Full article

Background/Objectives: SHP2 (PTPN11) is a key regulator of RAS/MAPK signaling and a well-validated target in cancer and developmental disorders. Designing ligands for its catalytic site is challenging due to the pocket’s intrinsic flexibility and the presence of conserved structural water molecules critical for ligand recognition, which limits traditional discovery approaches. This study aimed to systematically identify and prioritize novel SHP2-binding candidates using a computational strategy that accounts for these challenges. Methods: An integrative computational workflow was applied, combining water-aware docking, large-scale virtual screening of 714,409 compounds, MM/GBSA binding free-energy analysis, AI-driven chemical space modeling using ChemBERTa, and microsecond-scale molecular dynamics (MD) simulations. The high-resolution catalytic PTP domain of SHP2 structure was analyzed to identify conserved water molecules (W711, W716, W726, W776) essential for reproducing the crystallographic binding mode of the reference ligand 3LU. Candidates were prioritized based on docking scores, physicochemical criteria, structural inspection, MM/GBSA energetic profiles, and occupancy of distinct chemical space regions. Results: Seven compounds were selected. SwissADME analysis confirmed favorable drug-likeness and GI absorption, with no BBB permeation. ChemBERTa embeddings revealed substantial structural novelty relative to known SHP2 inhibitors. 1 μs molecular dynamics simulations suggested stable binding of compound 4 (2-(3-methyl-2,6-dioxopurin-7-yl)acetate) and persistent interactions with the conserved water network. MM/GBSA evaluation subsequently highlighted its energetically coherent profile. Conclusions: The workflow prioritizes compound 4 as a promising and structurally innovative SHP2-binding candidate. This integrative strategy provides a generalizable approach for targeting proteins with flexible pockets, critical water networks, and limited scaffold diversity, offering a roadmap for challenging computational ligand-prioritization projects. Full article

Background: Terahertz (THz) waves exhibit both photon-like and electron-like properties, showing emerging potential in biomedical applications. Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin tumors. Studies have reported that THz waves can induce apoptosis in cancer cells or ablate tumor tissues. Our previous studies also confirmed that 0.1 THz radiation could significantly promote apoptosis in cutaneous melanoma cells, while it had no apparent effect on fibroblast viability, proliferation, migration, and apoptosis. However, the effects of 0.1 THz radiation on CSCC cells have not yet been explored. Furthermore, there remains a lack of investigation into the structural and functional effects on fibroblasts. Therefore, it is necessary to conduct a systematic study to evaluate the influence of 0.1 THz radiation on both CSCC cells and fibroblasts in order to better understand its potential therapeutic applications in the treatment of skin cancer. Purpose: This study aims to explore the biological effects of 0.1 THz radiation on SCC-7 cells and to uncover the molecular mechanisms underlying THz-induced apoptosis, as well as its potential effect on L-929 cells. Methods: Cell viability was evaluated through the CCK-8 assay, while cell cycle distribution was analyzed with the DNA content detection kit. Wound healing assays were performed to assess cell migration, and Annexin V-FITC staining was used to detect apoptosis. Caspase-3 activity was measured using the caspase-3 activity assay kit. Cell morphology was observed using the Atomic Force Microscope (AFM) and the Transmission Electron Microscopy (TEM). Alterations in membrane potential were detected with the M09 membrane potential probe kit, and intracellular Ca²⁺ levels were quantified using the Fluo-8 AM fluorescent probe. Mitochondrial permeability transition pore (mPTP) opening was assessed with the MPTP detection kit, mitochondrial membrane potential changes were measured using the JC-1 probe kit, and cellular ATP levels were measured with the enhanced ATP assay kit. Subsequently, proteomic analysis was performed. Intracellular reactive oxygen species (ROS) levels were quantified with the ROS detection kit, and cytochrome c (Cyt c) release was quantified using the mouse Cyt c ELISA kit. Apoptosis-inducing factor (AIF) expression was analyzed at both mRNA and protein levels by quantitative real-time PCR (qPCR) and Western blot. AIF expression in CSCC tissues was further evaluated based on the GSE42677 and GSE45164 databases. Finally, cyclosporin A (CsA) was used to inhibit mPTP, and in combination with the iMAC inhibitor, the Aifm1 expression and Cyt c release were examined. Results: Our results showed that THz waves significantly disrupted the membrane integrity of SCC-7 cells and induced mitochondrial structural and functional damage. This resulted in a significant increase in ROS levels and the activation of mPTP and the mitochondrial apoptosis channel (MAC). THz radiation promoted the release of Cyt c and AIF from mitochondria, triggering a noncanonical caspase-3-dependent apoptosis pathway. Notably, L-929 cells did not show significant phenotypic or apoptotic changes under the same irradiation conditions. Bioinformatics analysis of the Gene Expression Omnibus (GEO) database revealed that AIF expression was significantly altered in CSCC tissues compared to normal skin tissues. Conclusions: These findings indicated that 0.1 THz radiation effectively induced apoptosis in SCC-7 cells by triggering mitochondrial dysfunction and ROS generation, which led to the release of AIF. Furthermore, the dysregulation of AIF in CSCC tissues suggested its potential as a promising biomarker. These results provided important molecular insights into the therapeutic potential of THz radiation, particularly for the treatment of cutaneous squamous cell carcinoma. Full article

Precise time synchronization is foundational for future intelligent transportation systems (ITS), where safety-critical functions like cooperative Vehicle-to-Everything (V2X) communication and multi-sensor fusion demand a leap from sub-microsecond- to nanosecond-level precision. Standard protocols like the Precision Time Protocol (PTP) are limited by inherent errors (e.g., timestamping inaccuracies and clock drift) that are typically only solvable with expensive hardware upgrades. This paper proposes a cost-effective, software-based solution. We introduce a novel method that leverages deep reinforcement learning (DRL) to actively predict and compensate for these synchronization errors in real time. An experimental environment is constructed to rigorously evaluate the performance of the proposed method. The results demonstrate that our approach achieves a significant leap in synchronization accuracy, showcasing its potential to meet the stringent timing demands of future intelligent transportation. Full article

With global cancer cases projected to reach 35 million by 2050 and drug resistance to existing chemotherapeutic drugs remaining a significant threat in cancer therapy, accounting for up to 90% of chemotherapy failures, the search for novel anticancer compounds continues to be increasingly important. This systematic review (2021–2025) examined the role of thiazoles and 4-thiazolidinones/thiazolidinediones as popular scaffolds in existing anticancer drug design. While researchers continue to focus on well-established molecular targets, such as EGFR, VEGFR-2, and tubulin, there is a notable difference regarding other preferred choices for thiazoles and 4-thiazolidinones/thiazolidinediones. Among analyzed mechanisms of anticancer activity notably favored for thiazoles was the inhibition of serine/threonine protein kinases (CDK-2, BRAF^V600E), while for 4-thiazolidinones/thiazolidinediones more studied were ROS generation and PPARγ activation. Furthermore, less-researched mechanisms of anticancer activity with no FDA-approved drugs such as PTP1B, SIRT2, PKM2, eIF4E, CA XI and XII inhibition for thiazole derivatives and pan-PIM kinase and BAG3 protein inhibition for 4-thiazolidinones/thiazolidinediones were evaluated as well. Notable was the popularity of the multi-targeting approach for modern drug design, with ~30% reporting two or more targets for their compounds. Despite these advancements, the review identified critical gaps in ADMET evaluations, safety analyzing against normal human cells and the lack of mechanistic studies connecting the targeted protein and the compounds anticancer effects. Full article

Background/Objectives: The clinical management of bladder cancer is severely impeded by high recurrence rates and the rapid emergence of chemoresistance, necessitating the discovery of novel therapeutic agents with distinct mechanisms of action. Dehydrodiisoeugenol (DHE), a bioactive neolignan, exhibits potent anti-tumor efficacy, yet its direct molecular targets and mode of action remain elusive. Methods: To deconvolute the mechanism of DHE, we integrated a phenotypic screening approach using 2D cell lines and 3D patient-derived organoids with a chemoproteomics-based activity-based protein profiling (ABPP) strategy. We synthesized a functionalized photoaffinity probe to capture the specific interactome of DHE under physiological conditions and validated targets via cellular thermal shift assays (CETSA), quantitative mass spectrometry, and 100 ns molecular dynamics (MD) simulations. Results: DHE exhibited potent dose-dependent cytotoxicity in bladder cancer cells, with IC50 values of 39.23 μM in T24 and 34.58 μM in 5637 cells. In 3D patient-derived organoids, DHE significantly reduced viability (p < 0.0001). Using a dual-filtering ABPP strategy, we identified 65 high-confidence candidate targets, prioritizing PTPN1 (PTP1B) as the primary functional interactor. Comparative molecular docking and 100 ns MD analyses showed that multiple stereoisomers of DHE could adopt plausible PTPN1-binding modes. Mechanistically, organoid proteomics indicated that DHE engagement with PTPN1 disrupts ER membrane homeostasis, thereby modulating the PI3K-Akt signaling axes. Conclusions: These findings establish PTPN1 as a critical druggable vulnerability in bladder cancer and define the molecular basis for the therapeutic potential of DHE. This study highlights the power of combining chemoproteomics with physiological 3D models to accelerate the translation of natural products into precision cancer therapies. Full article

Accurate time synchronization is essential in distributed electrical signal monitoring, where phase coherence and event correlation depend on precise timing agreement between acquisition nodes. Conventional approaches often rely on a single synchronization source, typically internet-based Network Time Protocol (NTP) or GPS-disciplined clocks, which is impractical in isolated, offline, or cost-sensitive scenarios. This paper introduces an autonomous offline synchronization architecture for multi-node monitoring systems built on Raspberry Pi 5 (RPI5) platforms connected to a private Ethernet network. Instead of depending on one timing method, the system integrates several complementary mechanisms: battery-backed RTC persistence via the J5 interface, deterministic orchestration through systemd services, automated boot time recovery, chrony-managed NTP discipline, and Precision Time Protocol (PTP) hardware timestamping using PTP Hardware Clock (PHC). Synchronization performance is validated through continuous multi-day measurements of long-term stability, inter-node phase coherence, and short-term jitter. Controlled power-loss scenarios are also included to verify recovery behavior. The system maintains sub-microsecond alignment between nodes using only commodity hardware and no external time source. To further confirm inter-node timestamp alignment at the signal level, both hardware-based reference signal injection and software-based synchronized signal emulation are employed, providing ground-truth validation alongside scalable and reproducible evaluation. The results show that low-cost embedded hardware can support reliable, long-duration synchronization in fully offline installations. Full article

A novel hydraulic circuit, the Modular Hydraulic Servo Booster (MHSB) is applied to redundant hydraulic manipulators. The MHSB uses multiple pumps and valves to drive multiple actuators to significantly improve energy efficiency compared with conventional servo-valve systems. Our previous work has proposed a control strategy that incorporates energy-optimal trajectory planning and operation mode switching using a graph search algorithm to perform point-to-point (PTP) tasks for manipulators. This paper extends our previous study by constructing an optimal-posture table that incorporates manipulability. By using this table to evaluate the cost in graph search, we achieve real-time optimal trajectory planning and operation mode switching for redundant manipulators. Numerical simulation from different PTP tasks on a three-link manipulator (1-m length, 10-kg weight) validate the proposed method. Full article

Alcoholic liver disease (ALD), secondary to chronic alcohol abuse, encompasses a spectrum of liver disorders that progress from steatosis and hepatitis to fibrosis, cirrhosis, and acute-on-chronic liver failure. It poses a considerable global health burden due to its elevated rates of associated morbidity and mortality. The rising prevalence of ALD, coupled with the lack of approved pharmacotherapies, presents considerable unmet clinical needs. In this study, long-chain acyl-CoA synthetase 4 (ACSL4) was identified as a pathogenic driver in the context of chronic alcohol consumption. Hepatocyte Acsl4 ablation mitigated key pathological manifestations in Gao-Binge model mice, as evidenced by reduced inflammatory cell infiltration and attenuated lipid accumulation. Mechanistically, ACSL4 inhibition augmented cellular antioxidant defence through elevating gamma-glutamylcysteine (γ-GC) levels. In addition, γ-GC bound to and suppressed the expression of protein tyrosine phosphatase type IVA member 1 (PTP4A1). Both genetic silencing and pharmacological inhibition of PTP4A1 attenuated the activation of the downstream MAPK-NF-κB inflammatory cascade. Dronedarone, identified as a novel compound targeting ACSL4, demonstrated efficacy in ameliorating the progression of ALD. Overall, these findings elucidate a novel mechanism wherein ACSL4 modulates antioxidant responses via a small bioactive peptide, highlighting ACSL4 as a potential therapeutic target for ALD. Full article