Search Results (68,534)

The large intelligent surface (LIS) concept represents an architectural advance for enhancing the performance of 6G wireless communication systems. In this work, we address the problem of jointly selecting active panels and associating terminals to outputs of such active panels in a panel-based LIS framework to maximise the minimum signal-to-interference-and-noise ratio (SINR) across all terminals. Due to the nature of the mixed-integer linear programming (MILP) formulation, we propose an alternative approach based on a genetic algorithm (GA) that efficiently explores the solution space through tailored crossover via column swapping and adaptive mutation. We compare the GA’s performance against the CPLEX solver under various configurations and time constraints. The performance results show that the GA provides competitive solutions with reduced computational complexity, showcasing its potential for scalable LIS implementations with complex resource allocation. Full article

SARS-CoV-2 undergoes frequent mutations that drive viral evolution and genomic diversity, influencing transmissibility, immune escape, and disease severity. In this study, we performed whole-genome sequencing on SARS-CoV-2 isolates from patients in New York City and identified several globally rare mutations across multiple viral lineages. The isolates analyzed for rare mutations belonged to three lineages: B.1.1.7 (Alpha), B.1.526 (Iota), and B.1.623. We identified 16 rare mutations (global incidence <1000) in non-structural protein genes, including nsp2, nsp3, nsp4, nsp6, nsp8, nsp13, nsp14, ORF7a, and ORF8. Three of these mutations—located in nsp2, nsp13, and ORF8—have been reported in fewer than 100 individuals worldwide. We also detected five rare mutations in structural proteins (S, M, and N), including two—one in M and one in N—previously reported in fewer than 100 cases globally. We present clinical profiles of three patients, each infected with genetically distinct viral isolates from the three lineages studied. Furthermore, we illustrate a local transmission chain inferred from unique mutation patterns identified in the Omicron genome. These findings underscore the importance of whole-genome sequencing for detecting rare mutations, tracking community spread, and identifying emerging variants with clinical and public health significance. Full article

To enhance the electromagnetic performance of flat-wire permanent magnet synchronous motors, three different groove structures were designed for the rotor, and a multi-objective optimization algorithm combining a genetic algorithm (GA) with the TOPSIS method was proposed. Firstly, an 8-pole 48-slot flat-wire motor model was established, and the cogging torque was analytically calculated to compare the motor’s performance under different groove schemes. Secondly, global multi-objective optimization of the rotor groove dimensions was performed using a combined simulation approach involving Maxwell, Workbench, and Optislang, and the optimal rotor groove size structure was selected using the TOPSIS method. Finally, a comparative analysis of the motor’s performance under both rated-load and no-load conditions was conducted for the pre- and post-optimization designs, followed by verification of the mechanical strength of the optimized rotor structure. The research results demonstrate that the combined optimization approach utilizing the genetic algorithm and the TOPSIS method significantly enhances the torque characteristics of the motor. The computational results indicate that the average torque is increased to 165.32 N·m, with the torque ripple reduced from 28.37% to 13.32% and the cogging torque decreased from 896.88 mN·m to 187.9 mN·m. Moreover, the total distortion rates of the air-gap magnetic flux density and the no-load back EMF are significantly suppressed, confirming the rationality of the proposed motor design. Full article

Background/Objectives: Enterococci, particularly Enterococcus faecalis and Enterococcus faecium, are Gram-positive cocci that can cause severe infections in hospitalized patients. The rise of vancomycin-resistant enterococci (VRE) and vancomycin-variable enterococci (VVE) poses significant challenges in healthcare settings due to their resistance to multiple antibiotics. Methods: We conducted a point prevalence survey (PPS) to assess the prevalence of VRE and VVE colonization in hospitalized patients. Rectal swabs were collected from 160 patients and analyzed using molecular assays (MAs) and culture. Whole-genome sequencing (WGS) and core-genome multilocus sequence typing (cgMLST) were performed to identify the genetic diversity. Results: Of the 160 rectal swabs collected, 54 (33.7%) tested positive for the vanA and/or vanB genes. Culture-based methods identified 47 positive samples (29.3%); of these, 44 isolates were identified as E. faecium and 3 as E. faecalis. Based on the resistance profiles, 35 isolates (74.5%) were classified as VRE, while 12 (25.5%) were classified as VVE. WGS and cgMLST analyses identified seven clusters of E. faecium, with sequence type (ST) 80 being the most prevalent. Various resistance genes and virulence factors were identified, and this study also highlighted intra- and inter-ward transmission of VRE strains. Conclusions: Our findings underscore the potential for virulence and resistance of both the VRE and VVE strains, and they highlight the importance of effective infection control measures to prevent their spread. VVE in particular should be carefully monitored as they often escape detection. Integrating molecular data with clinical information will hopefully enhance our ability to predict and prevent future VRE infections. Full article

Background/Objectives: The increased risk of developing tendinopathies in athlete populations has led to investigations of several genes associated with tendon properties, suggesting that some individuals have a greater genetic predisposition for developing tendinopathies. The main purpose of this study was to investigate how the functional polymorphisms within the COL5A1, COL27A1 and TNC genes impact the risk of developing tendinopathies in high-level Croatian athletes. Methods: For this case–control genetic study, we recruited 63 high-level athletes with a diagnosis of tendinopathies and 92 healthy asymptomatic individuals as controls. All individuals were genotyped for three single-nucleotide polymorphisms (SNPs) within the COL5A1, COL27A1 and TNC genes using the pyrosequencing method. Results: TNC rs2104772 TT (p = 0.0089) and the T-T-T haplotype (p = 0.0234), constructed from rs12722, rs946053 and rs2104772, were significantly overrepresented in cases versus controls, implicating a predisposition for tendinopathies. COL27A1 rs946053 GG (p = 0.0118) and the G-A-C haplotype (p = 0.0424), constructed from rs12722, rs946053 and rs2104772, were significantly overrepresented in controls, implicating a protective role. Conclusions: These results further support associations between functional polymorphisms within the COL27A1 and TNC genes and the risk of tendinopathies in high-level athletes. Further research is needed to replicate these results in various populations and larger cohorts. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children and comprises four molecular subtypes—WNT, SHH, Group 3, and Group 4—each with distinct genetic, epigenetic, and metabolic features. Increasing evidence highlights the critical role of metabolic reprogramming and epigenetic alterations in driving tumor progression, therapy resistance, and clinical outcomes. This review aims to explore the interplay between metabolic and epigenetic mechanisms in medulloblastoma, with a focus on their functional roles and therapeutic implications. Methods: A comprehensive literature review was conducted using PubMed and relevant databases, focusing on recent studies examining metabolic pathways and epigenetic regulation in medulloblastoma subtypes. Particular attention was given to experimental findings from in vitro and in vivo models, as well as emerging preclinical therapeutic strategies targeting these pathways. Results: Medulloblastoma exhibits metabolic adaptations such as increased glycolysis, lipid biosynthesis, and altered amino acid metabolism. These changes support rapid cell proliferation and interact with the tumor microenvironment. Concurrently, epigenetic mechanisms—including DNA methylation, histone modification, chromatin remodeling, and non-coding RNA regulation—contribute to tumor aggressiveness and treatment resistance. Notably, metabolic intermediates often serve as cofactors for epigenetic enzymes, creating feedback loops that reinforce oncogenic states. Preclinical studies suggest that targeting metabolic vulnerabilities or epigenetic regulators—and particularly their combination—can suppress tumor growth and overcome resistance mechanisms. Conclusions: The metabolic–epigenetic crosstalk in medulloblastoma represents a promising area for therapeutic innovation. Understanding subtype-specific dependencies and integrating biomarkers for patient stratification could facilitate the development of precision medicine approaches that improve outcomes and reduce long-term treatment-related toxicity in pediatric patients. Full article

Recent studies have demonstrated the clinical potential of nucleic acid therapeutics (NATs). However, their efficient and scalable delivery remains a major challenge for both ex vivo and in vivo gene therapy. Microfluidic platforms have emerged as a powerful tool for overcoming these limitations by enabling precise intracellular delivery and consistent therapeutic carrier fabrication. This review examines microfluidic strategies for gene delivery at the cellular level. These strategies include mechanoporation, electroporation, and sonoporation. We also discuss the synthesis of lipid nanoparticles, polymeric particles, and extracellular vesicles for systemic administration. Unlike conventional approaches, which treat ex vivo and in vivo delivery as separate processes, this review focuses on integrated microfluidic systems that unify these functions. For example, genetic materials can be delivered to cells that secrete therapeutic extracellular vesicles (EVs), or engineered cells can be encapsulated within hydrogels for implantation. These strategies exemplify the convergence of gene delivery and carrier engineering. They create a single workflow that bridges cell-level manipulation and tissue-level targeting. By synthesizing recent technological advances, this review establishes integrated microfluidic platforms as being fundamental to the development of next-generation NAT systems that are scalable, programmable, and clinically translatable. Full article

Electromagnetic pneumatic microvalves, widely used in knitting machines, typically operate based on a spring-return mechanism. When the coil is energized, the electromagnetic force overcomes the spring force to attract the armature, opening the valve. Upon de-energization, the armature returns to its original position under the restoring force of the spring, closing the valve. However, most existing electromagnetic microvalves adopt a radially asymmetric magnetic yoke design, which generates additional radial forces during operation, leading to armature misalignment or even sticking. Additionally, the inductance effect of the coil causes a significant delay in the armature release response, making it difficult to meet the knitting machine’s requirements for rapid response and high reliability. To address these issues, this paper proposes an improved electromagnetic microvalve design. First, the magnetic yoke structure is modified to be radially symmetric, eliminating unnecessary radial forces and preventing armature sticking during operation. Second, a permanent magnet assist mechanism is introduced at the armature release end to enhance release speed and reduce delays caused by the inductance effect. The effectiveness of the proposed design is validated through electromagnetic numerical simulations, and a multi-objective genetic algorithm is further employed to optimize the geometric dimensions of the electromagnet. The optimization results indicate that, while maintaining the fundamental power supply principle of conventional designs, the new microvalve structure achieves a pull-in time comparable to traditional designs during engagement but significantly reduces the release response time by approximately 80.2%, effectively preventing armature sticking due to radial forces. The findings of this study provide a feasible and efficient technical solution for the design of electromagnetic microvalves in textile machinery applications. Full article

Acacia mearnsii De Wild. has been introduced to over 150 countries for its economic value. However, it easily escapes from plantations and establishes monospecific stands across plains, hills, valleys, and riparian habitats, including protected areas such as national parks and forest reserves. Due to its negative ecological impact, A. mearnsii has been listed among the world’s 100 worst invasive alien species. This species exhibits rapid stem growth in its sapling stage and reaches reproductive maturity early. It produces a large quantity of long-lived seeds, establishing a substantial seed bank. A. mearnsii can grow in different environmental conditions and tolerates various adverse conditions, such as low temperatures and drought. Its invasive populations are unlikely to be seriously damaged by herbivores and pathogens. Additionally, A. mearnsii exhibits allelopathic activity, though its ecological significance remains unclear. These characteristics of A. mearnsii may contribute to its expansion in introduced ranges. The presence of A. mearnsii affects abiotic processes in ecosystems by reducing water availability, increasing the risk of soil erosion and flooding, altering soil chemical composition, and obstructing solar light irradiation. The invasion negatively affects biotic processes as well, reducing the diversity and abundance of native plants and arthropods, including protective species. Eradicating invasive populations of A. mearnsii requires an integrated, long-term management approach based on an understanding of its invasive mechanisms. Early detection of invasive populations and the promotion of public awareness about their impact are also important. More attention must be given to its invasive traits because it easily escapes from cultivation. Full article

Automated quality control plays a critical role in modern industries, particularly in environments that handle large volumes of packaged products requiring fast, accurate, and consistent inspections. This work presents an anomaly detection system for candle jars commonly used in industrial and commercial applications, where obtaining labeled defective samples is challenging. Two anomaly detection strategies are explored: (1) a baseline model using convolutional neural networks (CNNs) as an end-to-end classifier and (2) a hybrid approach where features extracted by CNNs are fed into One-Class classification (OCC) algorithms, including One-Class SVM (OCSVM), One-Class Isolation Forest (OCIF), One-Class Local Outlier Factor (OCLOF), One-Class Elliptic Envelope (OCEE), One-Class Autoencoder (OCAutoencoder), and Support Vector Data Description (SVDD). Both strategies are trained primarily on non-defective samples, with only a limited number of anomalous examples used for evaluation. Experimental results show that both the pure CNN model and the hybrid methods achieve excellent classification performance. The end-to-end CNN reached 100% accuracy, precision, recall, F1-score, and AUC. The best-performing hybrid model CNN-based feature extraction followed by OCIF also achieved 100% across all evaluation metrics, confirming the effectiveness and robustness of the proposed approach. Other OCC algorithms consistently delivered strong results, with all metrics above 95%, indicating solid generalization from predominantly normal data. This approach demonstrates strong potential for quality inspection tasks in scenarios with scarce defective data. Its ability to generalize effectively from mostly normal samples makes it a practical and valuable solution for real-world industrial inspection systems. Future work will focus on optimizing real-time inference and exploring advanced feature extraction techniques to further enhance detection performance. Full article

Contact unmodified antisense DNA biotechnology (CUADb), developed in 2008, employs short antisense DNA oligonucleotides (oligos) as a novel approach to insect pest control. These oligonucleotide-based insecticides target pest mature rRNAs and/or pre-rRNAs and have demonstrated high insecticidal efficacy, particularly against sap-feeding insect pests, which are key vectors of plant DNA viruses and among the most economically damaging herbivorous insects. To further explore the potential of CUADb, this study evaluated the insecticidal efficacy of short 11-mer antisense DNA oligos against Coccus hesperidum, in comparison with long 56-mer single-stranded and double-stranded DNA sequences. The short oligos exhibited higher insecticidal activity. By day 9, the highest mortality rate (97.66 ± 4.04%) was recorded in the Coccus-11 group, while the most effective long sequence was the double-stranded DNA in the dsCoccus-56 group (77.09 ± 6.24%). This study also describes the architecture of the DNA containment (DNAc) mechanism, highlighting the intricate interactions between rRNAs and various types of DNA oligos. During DNAc, the Coccus-11 treatment induced enhanced ribosome biogenesis and ATP production through a metabolic shift from carbohydrates to lipid-based energy synthesis. However, this ultimately led to a ‘kinase disaster’ due to widespread kinase downregulation resulting from insufficient ATP levels. All DNA oligos with high or moderate complementarity to target rRNA initiated hypercompensation, but subsequent substantial rRNA degradation and insect mortality occurred only when the oligo sequence perfectly matched the rRNA. Both short and long oligonucleotide insecticide treatments led to a 3.75–4.25-fold decrease in rRNA levels following hypercompensation, which was likely mediated by a DNA-guided rRNase, such as RNase H1, while crucial enzymes of RNAi (DICER1, Argonaute 2, and DROSHA) were downregulated, indicating fundamental difference in molecular mechanisms of DNAc and RNAi. Consistently, significant upregulation of RNase H1 was detected in the Coccus-11 treatment group. In contrast, treatment with random DNA oligos resulted in only a 2–3-fold rRNA decrease, consistent with the normal rRNA half-life maintained by general ribonucleases. These findings reveal a fundamental new mechanism of rRNA regulation via complementary binding between exogenous unmodified antisense DNA and cellular rRNA. From a practical perspective, this minimalist approach, applying short antisense DNA dissolved in water, offers an effective, eco-friendly and innovative solution for managing sternorrhynchans and other insect pests. The results introduce a promising new concept in crop protection: DNA-programmable insect pest control. Full article

The compound effects of extreme climate change and intensive urban development have led to more frequent urban inundation, highlighting the urgent need for the fine-scale evaluation of stormwater drainage system performance in high-density urban built-up areas. A typical basin, located in Shenzhen, was selected, and a pipe–river coupled SWMM was developed and calibrated via a genetic algorithm to simulate the storm drainage system. Design storm scenario analyses revealed that regional inundation occurred in the central area of the basin and the enclosed culvert sections of the midstream river, even under a 0.5-year recurrence period, while the downstream open river channels maintained a substantial drainage capacity under a 200-year rainfall event. To systematically identify bottleneck zones, two novel metrics, namely, the node cumulative inundation volume and the conduit cumulative inundation length, were proposed to quantify the local inundation severity and spatial interactions across the drainage network. Two critical bottleneck zones were selected, and strategic improvement via the cross-sectional expansion of pipes and river culverts significantly enhanced the drainage efficiency. This study provides a practical case study and transferable technical framework for integrating hydraulic modeling, spatial analytics, and targeted infrastructure upgrades to enhance the resilience of drainage systems in high-density urban environments, offering an actionable framework for sustainable urban stormwater drainage system management. Full article

Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal genetic disease caused by a silent mutation in the LMNA gene, leading to the production of progerin, a defective prelamin A variant. Progerin accumulation disrupts nuclear integrity, alters chromatin organization, and drives systemic cellular dysfunction. While autophagy and inflammation are key dysregulated pathways in HGPS, the role of microRNAs (miRNAs) in these processes remains poorly understood. Methods: We performed an extensive literature review to identify miRNAs involved in autophagy and inflammation. Through stem-loop RT-qPCR in aging HGPS and control fibroblast strains, we identified significant miRNAs and focused on the most prominent one, miR-181a-5p, for in-depth analysis. We validated our in vitro findings with miRNA expression studies in skin biopsies from an HGPS mouse model and conducted functional assays in human fibroblasts, including immunofluorescence staining, β-Galactosidase assay, qPCR, and Western blot analysis. Transfection studies were performed using an miR-181a-5p mimic and its inhibitor. Results: We identified miR-181a-5p as a critical regulator of premature senescence in HGPS. miR-181a-5p was significantly upregulated in HGPS fibroblasts and an HGPS mouse model, correlating with Sirtuin 1 (SIRT1) suppression and induction of senescence. Additionally, we demonstrated that TGFβ1 induced miR-181a-5p expression, linking inflammation to miRNA-mediated senescence. Inhibiting miR-181a-5p restored SIRT1 levels, increased proliferation, and alleviated senescence in HGPS fibroblasts, supporting its functional relevance in disease progression. Conclusions: These findings highlight the important role of miR-181a-5p in premature aging and suggest its potential as a therapeutic target for modulating senescence in progeroid syndromes. Full article

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article