Search Results (5,344)

Background/Objectives: Ovarian cancer (OC) remains one of the most lethal malignancies of the female reproductive system. Glucose oxidase (GOx) has emerged as a potential therapeutic agent in cancer treatment by inducing tumor starvation through glucose depletion. Nonetheless, its clinical application is constrained due to its systemic toxicity, immunogenicity, poor in vivo stability, and short half-life. These challenges can be addressed through nanotechnology; in particular, biogenic mesoporous silica nanoparticles (MSNs) offer promise as drug delivery systems (DDSs) that enhance therapeutic efficacy while minimizing side effects. Methods: Biogenic MSNs were extracted from the Equisetum myriochaetum plant via acid digestion, functionalized with 3-aminopropiltrietoxysilane (APTES) and glutaraldehyde (GTA), and loaded with GOx. The free and immobilized MSNs were characterized using FTIR, DLS, XRD, SEM/EDX, and BET techniques. A colorimetric approach was employed to quantify the enzymatic activity of both the free and immobilized GOx. The MTT assay was employed to assess the viability of SKOV3 cells. The obtained IC₅₀ concentration of the nanoformulation was administered to SKOV3 cells to analyze the expression of cancer-related genes using RT-qPCR. Results: IC₅₀ values of 60.77 ng/mL and 111.6 µg/mL were ascertained for the free and immobilized GOx, respectively. Moreover, a significant downregulation of the oncogene β-catenin (CTNNB1) was detected after 24 h with the nanoformulation. Conclusions: Our findings indicate that GOx-loaded biogenic MSNs may serve as a potential therapeutic agent for ovarian cancer. This is, to the best of our knowledge, the first report exploring the effect of GOx-loaded biogenic MSNs on SKOV3 cells. Full article

Lesch–Nyhan disease (LND) is associated with a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity due to mutations in the HPRT1 gene. Although the physiopathology of LND-related neurological manifestations remains unknown, a defective neuronal developmental process is the most widely accepted hypothesis. We generated an HPRT-deficient line from the pluripotent human embryonic cell line NT2/D1 by CRISPR-Cas9 and induced its differentiation along neuroectodermal lineages by retinoic acid treatment. As levels of folic acid in the culture media may affect results in LND models, we employed physiological levels of folate. The effect of HPRT deficiency on neural development-related gene expression was evaluated using two methodological approaches: a directed qPCR array of genes related to neuronal differentiation, and global gene expression by RNAseq. HPRT-deficient pluripotent cells presented altered expression of genes related to pluripotency in human embryonic stem cells, such as DPPA3 and CFAP95, along with genes of the homeobox gene family. HPRT-deficient pluripotent cells were able to differentiate along neuro-ectodermal lineages but presented consistent dysregulation of several genes from the homeobox gene family, including EN1 and LMX1A. GO enrichment analysis of up- and downregulated genes in HPRT-deficient cells showed that the most significant biological processes affected are related to development and nervous system development. Full article

More than seventy-five years ago, R. Hanbury Brown and R. Q. Twiss performed the first experiments in quantum optics. At the outset, their results showed great promise for the field of astronomical science, featuring inexpensive hardware, immunity to atmospheric turbulence, and enormous interferometry baselines. This was put to good use for the determination of stellar diameters up to the present time. However, for two-dimensional imaging with faint objects, the integration times are prohibitive. Recently, in a sequence of papers, the present author developed a stochastic search algorithm to remove this roadblock, reducing millions of hours to minutes or seconds. Also, the author’s paper entitled “The Rise of the Brown-Twiss Effect” summarized the search algorithm and emphasized the mathematical proofs of the algorithm. The current algorithm is a sequence of six lines of code. The goal of the present article is to streamline the algorithm in the form of a discrete-time dynamic system and to reduce the size of the state space. The previous algorithm used initial conditions that were randomly assorted pixel intensities. The intensities were mutually statistically independent and uniformly distributed over the range $\left[0,\delta \right)$, where $\delta$ is a (very small) positive constant. The present formulation employs a transformation requiring the uniformly distributed phase of the fast Fourier transform of the cross correlations of the data as initial conditions. We shall see that this strategy results in the simplest discrete-time dynamic system capable for exploring the alternate features and benefits of compartmental nonnegative dynamic systems. Full article

Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined with antiviral drugs like arbidol, especially for diseases such as Coronavirus disease. This study investigates the synergistic mechanisms between arbidol and components from TQG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro). Methods: We identified compounds from TQG via existing data. Multi-ligand molecular docking, pharmacokinetic/toxicity screening, and preliminary simulations were performed to assess potential synergistic compounds with arbidol. UPLC-Q-Exactive Orbitrap-MS verified the presence of these compounds. Extended simulations and in vitro assays, including Luciferase and surface plasmon resonance, validated the findings. Results: Five compounds interacted with arbidol in synergy based on docking and preliminary dynamics simulation results. Only Baicalein (HQA004) could be identified in the herbal remedy by untargeted metabolomics, with ideal pharmacokinetic properties, and as a non-toxic compound. Extended simulations revealed that HQA004 enhanced arbidol’s antiviral activity via a “Far” Addition Mechanism #2, with an optimal 2:1 arbidol:HQA004 ratio. The movements of arbidol (diffusion and intramolecular conformational shifts) in the system were significantly reduced by HQA004, which may be the main reason for the synergism that occurred. In vitro experiments confirmed an increased inhibition of M^pro by the combination. Conclusions: HQA004 demonstrated synergistic potential with arbidol in inhibiting M^pro. The development of combination therapies integrating Western and herbal medicine is supported by these findings for effective antiviral treatments. Full article

Background: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA–mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA–mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA–mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results: The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/TNF and miR-190a-3p/IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors (IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions: Consequently, miR-190a-3p/IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity. Full article

Introduction: Scattering of kernels due to angular dehiscence is a key bottleneck in mechanized harvesting of oilseed rape. Materials and Methods: In this study, a dual-track “genotype–phenotype” screening strategy was established by innovatively integrating high-throughput KASP molecular marker technology and a standardized random collision phenotyping system for the complex quantitative trait of angular resistance. Results: Through the systematic evaluation of 634 oilseed rape hybrid progenies, it was found that the KASP marker S12.68, targeting the cleavage resistance locus (BnSHP1) on chromosome C9, achieved a 73.34% introgression rate (465/634), which was significantly higher than the traditional breeding efficiency (<40%). Phenotypic characterization screened seven excellent resources with cracking resistance index (SRI) > 0.6, of which four reached the high resistance standard (SRI > 0.8), including the core materials NR21/KL01 (SRI = 1.0) and YuYou342/KL01 (SRI = 0.97). Six breeding intermediate materials (44.7–48.7% oil content, mycosphaerella resistance MR grade or above) were created, combining high resistance to chipping and excellent agronomic traits. For the first time, it was found that local germplasm YuYou342 (non-KL01-derived line) was purely susceptible at the S12.68 locus (SRI = 0.86), but its angiosperm vascular bundles density was significantly increased by 37% compared with that of the susceptible material 0911 (p < 0.01); and the material 187308 (SRI = 0.78), although purely susceptible at S12.68, had a 2.8-fold downregulation in expression of the angiosperm-related gene, BnIND1, and a 2.8-fold downregulation of expression of the angiosperm-related gene, BnIND1. expression was significantly downregulated 2.8-fold (q < 0.05), indicating the existence of a novel resistance mechanism independent of the primary effector locus. Conclusions: The results of this research provide an efficient technical platform and breakthrough germplasm resources for oilseed rape crack angle resistance breeding, which is of great practical significance for promoting the whole mechanized production. Full article

Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and thirteen P genotypes have been identified, with G9, G5, G3, and G4 emerging as predominant circulating strains. The limited cross-protective immunity between genotypes compromises vaccine efficacy, necessitating genotype surveillance to guide vaccine development. While conventional molecular assays demonstrate sensitivity, they lack rapid genotyping capacity and face technical limitations. To address this, we developed a novel diagnostic platform integrating reverse transcription recombinase-aided amplification (RT-RAA) with CRISPR–Cas12a. This system employs universal primers for the simultaneous amplification of G4/G5/G9 genotypes in a single reaction, coupled with sequence-specific CRISPR recognition, achieving genotyping within 50 min at 37 °C with 10⁰ copies/μL sensitivity. Clinical validation showed a high concordance with reverse transcription quantitative polymerase chain reaction (RT-qPCR). This advancement provides an efficient tool for rapid viral genotyping, vaccine compatibility evaluation, and optimized epidemic control strategies. Full article

The analytical solutions for groundwater inflow into tunnels are usually developed under the condition of circular tunnels. However, real-world tunnels often have non-circular cross-sections, such as arched, lens-shaped, or egg-shaped profiles. Accurately assessing water inflow for these diverse tunnel shapes remains challenging. To address this gap, this study developed a closed-form analytical solution for water inflow into a deeply buried arched tunnel using the conformal mapping method. When the tunnel circumference degenerates to a circle, the analytical solution degenerates to the widely used Goodman’s equation. The solution also showed excellent agreement with numerical simulations carried out using COMSOL. Based on the analytical solution, the impact of various factors on water inflow Q was further discussed: (1) Q decreases as the boundary distance $D^{\ast }$ increases. And the boundary inclination angle ($\alpha -\pi /2$) significantly affects Q only when the boundary is close to the tunnel ($D^{\ast }<20$); (2) Q increases quickly with the upper arc radius $r_1^{\ast }$, while it shows minimal variation with the change in the lower arc radius $r_2^{\ast }$. The findings provide a theoretical foundation for characterizing water inflow into arched tunnels, thereby supporting improved tunnel planning and grouting system design. Full article

Background/Objectives: Concurrent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A and B viruses (IAV/IBV), and respiratory syncytial virus (RSV) necessitate rapid and precise differential laboratory diagnostic methods. This study aimed to evaluate the multiplex molecular diagnostic performance of the geneLEAD VIII system (Precision System Science Co., Ltd., Matsudo, Japan), a fully automated sample-to-result precision instrument, in conjunction with the VIASURE SARS-CoV-2, Flu & RSV Real Time PCR Detection Kit (CerTest Biotec, S.L., Zaragoza, Spain). Methods: The specific detection capabilities of SARS-CoV-2, IAV/IBV, and RSV genes were evaluated using virus-spiked saliva and nasal swab samples. Using saliva samples, the viral titer detection limits of geneLEAD/VIASURE and manual referent singleplex RT-qPCR assays were compared. The performance of geneLEAD/VIASURE in analyzing single- and multiple-infection models was scrutinized. The concordance between the geneLEAD/VIASURE and the manual assays was assessed. Results: The geneLEAD/VIASURE successfully detected all the virus genes in the saliva and nasal swab samples despite some differences in the Ct values. The viral titer detection limits in the saliva samples for SARS-CoV-2, IAV, IBV, and RSV using geneLEAD/VIASURE were 10⁰, ≤10⁻², 10⁰, and 10² TCID₅₀/mL, respectively, compared to ≤10⁻¹, ≤10⁰, ≤10⁰, and ≤10⁴ TCID₅₀/mL, respectively, in the manual assays. geneLEAD/VIASURE yielded similar Ct values in the single- and multiple-infection models, with some exceptions noted in the triple-infection models when low titers of RSV were spiked with high titers of the other viruses. The concordance between geneLEAD/VIASURE and the manual assays was high, with Pearson’s R² values of 0.90, 0.85, 0.92, and 0.95 for SARS-CoV-2, IAV, IBV, and RSV, respectively. Conclusions: geneLEAD/VIASURE is a reliable diagnostic tool for detecting SARS-CoV-2, IAV/IBV, and RSV in single- and multiple-infection scenarios. Full article

The endothelial glycocalyx (GCX) plays a crucial role in vascular health and integrity and influences many biochemical activities through mechanotransduction, in which heparan sulfate (HS) plays a major role. Endothelin-1 (ET-1) is a potent vasoregulator that binds to the endothelin B receptor (ETB) on endothelial cells (ECs), stimulating vasodilation, and to the endothelin A receptor on smooth muscle cells, stimulating vasoconstriction. While the shear stress (SS) dependence of ET-1 and HS is well documented, there is limited research documenting the SS dependence of the ETB. Understanding the SS dependence of the ETB is crucial for clarifying the role of hemodynamic forces in the endothelin system. We hypothesize that GCX HS regulates the expression of the ETB on the EC surface in an SS-dependent manner. Human lung microvascular ECs were exposed to SS in a parallel-plate flow chamber for 12 h. Damage to the GCX was simulated by treatment with 15 mU/mL heparinase-III during SS exposure. Immunostaining and qPCR were used to evaluate changes in ET-1, ETB, and HS expression. Results indicate that ETB expression is SS sensitive, with at least a 1.3-fold increase in ETB protein expression and a 0.6 to 0.4-fold-change decrease in ETB mRNA expression under SS. This discrepancy suggests post-translational regulation. In some cases, enzymatic degradation of HS attenuated the SS-induced increase in ETB protein, reducing the fold-change difference to 1.1 relative to static controls. This implies that ETB expression may be partially dependent on HS-mediated mechanotransduction, though inconclusively. Furthermore, ET-1 mRNA levels were elevated two-fold under SS without a corresponding rise in ET-1 protein expression or significant impact from HS degradation, implying that post-translational regulation of ET-1 occurs independently of HS. Full article

A real-time structural health monitoring (SHM) system of an airplane composite wing with adjustable damage is reported, where testing under realistic flight conditions is carried out in the controllable and repeatable environment of an industrial wind tunnel. An FBG-based sensing array monitors a debonded region, whose compromised structural strength is regained by a set of lockable fasteners. Damage tunability is achieved by loosening some of or all these fasteners. Real-time analysis of the data collected involves Principal Component Analysis, followed by Hotelling’s T-squared and Q measures. With previously set criteria, real-time data collection and processing software can declare the structural health status as normal or abnormal. During testing, the system using the Q measure successfully identified the initiation of the damage and its extent, while the T-squared one returned limited outcomes. Full article

In recent years, distributed energy power supply systems have been widely used in remote areas and extreme environments. However, the intermittent and uncertain output power may cause power grid fluctuations, leading to higher harmonics in electromechanical equipment, especially motors. For permanent magnet synchronous motor (PMSM) systems, an electromagnetic (EM) vibration can cause problems such as energy loss and mechanical wear. Therefore, it is necessary to design control algorithms that can effectively suppress EM vibration. To this end, a vibration suppression algorithm for fractional-slot permanent magnet synchronous motors based on a d-axis current injection is proposed in this paper. Firstly, this paper analyzes the radial electromagnetic force of the fractional-slot PMSM to identify the main source of EM vibration in fractional-slot PMSMs. Based on this, the intrinsic relationship between the EM vibration of fractional-slot PMSMs and the d-axis and q-axis currents is explored, and a method for calculating the d-axis current to suppress the vibration is proposed. Experimental verification shows that the proposed algorithm can effectively suppress EM vibration. Full article

The fast expansion of cloud computing has raised carbon emissions and energy usage in cloud data centers, so creative solutions for sustainable resource management are more necessary. This work presents a new algorithm—Carbon-Aware, Energy-Efficient, and SLA-Compliant Virtual Machine Placement using Deep Q-Networks (DQNs) and Agglomerative Clustering (CARBON-DQN)—that intelligibly balances environmental sustainability, service level agreement (SLA), and energy efficiency. The method combines a deep reinforcement learning model that learns optimum placement methods over time, carbon-aware data center profiling, and the hierarchical clustering of virtual machines (VMs) depending on resource constraints. Extensive simulations show that CARBON-DQN beats conventional and state-of-the-art algorithms like GRVMP, NSGA-II, RLVMP, GMPR, and MORLVMP very dramatically. Among many virtual machine configurations—including micro, small, high-CPU, and extra-large instances—it delivers the lowest carbon emissions, lowered SLA violations, and lowest energy usage. Driven by real-time input, the adaptive decision-making capacity of the algorithm allows it to dynamically react to changing data center circumstances and workloads. These findings highlight how well CARBON-DQN is a sustainable and intelligent virtual machine deployment system for cloud systems. To improve scalability, environmental effect, and practical applicability even further, future work will investigate the integration of renewable energy forecasts, dynamic pricing models, and deployment across multi-cloud and edge computing environments. Full article

With the increasing penetration of distributed generation and the diversification of electrical equipment, distribution networks face issues like three-phase unbalance and harmonic currents, while the voltage stability and inertia of the grid-connected system also decrease. A certain amount of energy storage is needed in a Distribution Static Synchronous Compensator (DSTATCOM) to manage power quality and actively support voltage and inertia in the network. This paper first addresses the limitations of traditional $dq0$ compensation algorithms in effectively filtering out negative-sequence twice-frequency components. An improved $dq0$ compensation algorithm is proposed to reduce errors in detecting positive-sequence fundamental current under unbalanced three-phase conditions. Second, considering the impedance ratio characteristics of the distribution network, while reactive power voltage regulation is common, active power regulation is more effective in high-resistance distribution networks. A grid-forming model-based active and reactive power coordinated voltage regulation method is proposed. This method uses synchronous control to establish a virtual three-phase voltage internal electromotive force, forming a comprehensive compensation strategy that combines power quality improvement and active voltage support, exploring the potential of energy storage DSTATCOM applications in distribution networks. Finally, simulation and experimental results demonstrate the effectiveness of the proposed control method. Full article

Emergencies can occur unexpectedly and require immediate action, especially in aviation, where time pressure and uncertainty are high. This study focused on improving emergency evacuation in airport and aircraft scenarios using real-time decision-making support. A system based on the Asynchronous Advantage Actor–Critic (A3C) algorithm, an advanced deep reinforcement learning method, was developed to generate faster and more efficient evacuation routes compared to traditional models. The A3C model was tested in various scenarios, including different environmental conditions and numbers of agents, and its performance was compared with the Deep Q-Network (DQN) algorithm. The results showed that A3C achieved evacuations 43.86% faster on average and converged in fewer episodes (100 vs. 250 for DQN). In dynamic environments with moving threats, A3C also outperformed DQN in maintaining agent safety and adapting routes in real time. As the number of agents increased, A3C maintained high levels of efficiency and robustness. These findings demonstrate A3C’s strong potential to enhance evacuation planning through improved speed, adaptability, and scalability. The study concludes by highlighting the practical benefits of applying such models in real-world emergency response systems, including significantly faster evacuation times, real-time adaptability to evolving threats, and enhanced scalability for managing large crowds in high-density environments including airport terminals. The A3C-based model offers a cost-effective alternative to full-scale evacuation drills by enabling virtual scenario testing, supports proactive safety planning through predictive modeling, and contributes to the development of intelligent decision-support tools that improve coordination and reduce response time during emergencies. Full article