Search Results (1,807)

In this work, the load spectra acting in the vertical direction on the hub carriers and in the horizontal longitudinal direction on the drawbar of a trailed variable chamber round baler were evaluated. To this end, each hub carrier was instrumented with appropriately calibrated strain gauge bridges. Similarly, the baler was equipped with a dynamometric towing pin, instrumented with strain gauge sensors and calibrated in the laboratory, which replaced the original pin connecting the baler and the tractor during the in-field load acquisitions. In both cases, the calibration tests returned the relationship between applied forces and output signals of the strain gauge bridges. Multiple in-field load acquisitions were carried out under typical maneuvers and operating conditions. The synchronous acquisition of a video via an onboard camera and Global Positioning System (GPS) signal allowed to observe the behaviour of the baler in correspondence of particular trends of the vertical and horizontal loads and to point out the most demanding maneuver in view of the fatigue resistance of the baler. Finally, through the application of a rainflow cycle counting algorithm according to ASTM E1049-85, the load spectrum for each maneuver was derived. Full article

Fungal infections pose a significant yet under-recognised global health burden, affecting over one billion individuals annually and contributing to approximately 2.5 million direct deaths. The World Health Organisation (WHO) has recently reemphasised this issue through the publication of its Fungal Priority Pathogens List (FPPL) and its 2025 report evaluating current antifungal diagnostics and therapeutics. Among the most prevalent fungal pathogens is Trichophyton rubrum, an anthropophilic dermatophyte responsible for up to 70% of superficial fungal infections, including onychomycosis. The emergence of antifungal resistance further complicates management, necessitating the development of novel, effective, and sustainable treatment alternatives. Natural compounds are increasingly being explored for their antifungal potential due to their broad-spectrum activity and lower toxicity. Coconut oil has gained particular attention for its therapeutic properties attributed to medium-chain fatty acids (MCFAs), especially lauric acid. The aim of this study was to understand how innate and modified coconut oils can alter the rheological properties of Pluronic hydrogels while retaining antifungal activity for downstream application in treating fungal infections. Results identified hydrophobic interactions by FTIR and DSC between the hydrocarbon chains of the coconut triglycerides and the hydrophobic core of the Pluronic micelles, leading to gel stabilisation as identified by rheological analysis. Full article

Since the onset of the COVID-19 pandemic, remarkable progress has been made in the development of antiviral therapies for SARS-CoV-2. Several direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir/ritonavir, offer clinical benefits. These agents have significantly contributed to reducing the viral loads and duration of the illness, as well as the disease’s severity and mortality. However, despite these advances, important limitations remain. The continued emergence of resistant SARS-CoV-2 variants highlights the urgent need for adaptable and durable therapeutic strategies. Therefore, this review aims to provide an updated overview of the main antiviral strategies that are used and the discovery of new drugs against SARS-CoV-2, as well as the therapeutic limitations that have shaped clinical management in recent years. The major challenges include resistance associated with viral mutations, limited treatment windows, and unequal access to treatment. Moreover, there is an ongoing need to identify novel compounds with broad-spectrum activity, improved pharmacokinetics, and suitable safety profiles. Combination treatment regimens represent a promising strategy to increase the efficacy of treating COVID-19 while minimizing the potential for resistance. Ideally, these interventions should be safe, affordable, and easy to administer, which would ensure broad global access and equitable treatment and enable control of COVID-19 cases and preparedness for future threats. Full article

Background: Spectrin proteins are critical cytoskeleton components that maintain cellular structure and mediate intracellular transport. Pathogenic variants in SPTBN1, encoding βII-spectrin, have been associated with various neurodevelopmental disorders, including developmental delay, intellectual disability, autism spectrum disorder, and epilepsy. Here we report a Korean infant with infantile epileptic spasms syndrome (IESS) and an SPTBN1 mutation and provide a review of this mutation. Methods: The genomic data of the patient were analyzed by whole exome sequencing. A comprehensive literature review was conducted to identify and analyze all reported SPTBN1 variants, resulting in a dataset of 60 unique mutations associated with neurodevelopmental phenotypes. Case Presentation: A 10-month-old Korean female presented with IESS associated with a de novo heterozygous SPTBN1 mutation (c.785A>T; p.Asp262Val). The patient exhibited global developmental delay, microcephaly, hypotonia, spasticity, and MRI findings of diffuse cerebral atrophy and corpus callosum hypoplasia. Electroencephalography revealed hypsarrhythmia, confirming the diagnosis of IESS. Seizures persisted despite initial treatment with vigabatrin and steroids. Genetic analysis identified a likely pathogenic variant within the calponin homology 2 (CH2) domain of SPTBN1. Conclusions: This is the first report of an association between IESS and an SPTBN1 CH2 domain mutation in a Korean infant. This finding expands the clinical spectrum of SPTBN1-related disorders and suggests domain-specific effects may critically influence phenotypic severity. Further functional studies are warranted to elucidate the pathogenic mechanisms of domain-specific variants. Full article

Axial truncal dystonia can present as either flexion or extension, often with a tendency toward lateral movement. Flexion dystonia is more common and may represent a clinical spectrum associated with parkinsonism. In contrast, extensor trunk dystonia is less frequent and exhibits a diverse range of causes. In this paper, we reviewed the literature on axial extensor trunk dystonia. We identified 11 studies involving 49 patients, of which only 10 had idiopathic trunk dystonia. Treatment with botulinum neurotoxin A (BoNT/A) emerged as the most effective therapy; however, many studies did not provide detailed descriptions of the treatment (4/11) and follow-up periods were not specified or short term (up to one–two years). We present four new, well-documented patients with the idiopathic form of extensor trunk dystonia who were treated with BoNT/A with moderate to significant effect according to Global Clinical Impression scale (GCI) and Burke-Fahn-Marsden (BFM) dystonia scale. These cases include long-term follow-up for three patients, all without any adverse events. While the diagnostic process and treatment can be challenging, we recommend using BoNT/A with adjusted doses tailored to the appropriate muscle groups as a first-line treatment. Full article

Radio frequency (RF)-based wireless systems are broadly used in communication systems such as mobile networks, satellite links, and monitoring applications. These systems offer outstanding advantages over wired systems, particularly in terms of ease of installation. However, researchers are looking for safer alternatives as a result of worries about possible health problems connected to high-frequency radiofrequency transmission. Using the visible light spectrum is one promising approach; three cutting-edge technologies are emerging in this regard: Optical Camera Communication (OCC), Light Fidelity (Li-Fi), and Visible Light Communication (VLC). In this paper, we propose a Multiple-Input Multiple-Output (MIMO) modulation technology for Internet of Things (IoT) applications, utilizing an LED array and time-domain on-off keying (OOK). The proposed system is compatible with both rolling shutter and global shutter cameras, including commercially available models such as CCTV, webcams, and smart cameras, commonly deployed in buildings and industrial environments. Despite the compact size of the LED array, we demonstrate that, by optimizing parameters such as exposure time, camera focal length, and channel coding, our system can achieve up to 20 communication links over a 20 m distance with low bit error rate. Full article

The global antimicrobial resistance crisis demands innovative strategies to combat bacterial infections, including those caused by drug-sensitive pathogens that evade treatment through biofilm formation or metabolic adaptations. Here, we demonstrate that Squama Manitis extract (SME)—a traditional Chinese medicine component—exhibits broad-spectrum bactericidal activity against clinically significant pathogens, including both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) species (MIC = 31.25 mg/mL), achieving significant reduction in bacterial viability within 24 h. Through integrated multi-omics analysis combining scanning electron microscopy and RNA sequencing, we reveal SME’s unprecedented tripartite mechanism of action: (1) direct membrane disruption causing cell envelope collapse, (2) metabolic paralysis through coordinated suppression of TCA cycle and fatty acid degradation pathways, and (3) inhibition of DNA repair systems (SOS response and recombination downregulation). Despite its potent activity, SME shows low cytotoxicity toward mammalian cells (>90% viability) and can penetrate Gram-negative outer membranes. These features highlight SME’s potential to address drug-resistant infections through synthetic lethality across stress response, energy metabolism, and DNA integrity pathways. While advocating for synthetic alternatives to endangered animal products, this study establishes SME as a polypharmacological template for resistance-resilient antimicrobial design, demonstrating how traditional knowledge and modern systems biology can converge to guide sustainable anti-infective development. Full article

Objective: Retained primitive reflexes are associated with delayed motor and behavioral development in children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This study examined the effects of a 12-week structured exercise intervention on reflex integration, motor coordination, and socio-behavioral outcomes in these populations. Method: Fifteen children with ASD (13 boys, 2 girls) and twelve with ADHD (8 boys, 4 girls), aged 6–12 years, participated in rhythmic, balance, and coordination-based exercises. Primitive reflexes, including the asymmetrical tonic neck reflex (ATNR), were assessed using standardized protocols, and fine motor coordination was evaluated using the Finger and Thumb Opposition Test (FOT). Behavioral outcomes were measured using the Social Responsiveness Scale-2 (SRS-2) for the ASD group and the Conners 3 for the ADHD group. Results: The ASD group showed significant reductions in left-standing ATNR retention scores (p = 0.012) and improvements in right-hand FOT scores (p = 0.023). In the ADHD group, significant improvements were also observed in right-hand FOT scores (p = 0.007). Furthermore, Conners 3 Total and Global Index scores significantly decreased in the ADHD group (p = 0.016 and 0.020, respectively). Reflex retention patterns appeared broader and more bilateral in ASD than in ADHD, suggesting distinct motor developmental profiles. Conclusions: Short-term rhythmic, balance, and whole-body coordination exercise interventions may support behavioral and motor development in children with ASD and ADHD. Tailored programs emphasizing reflex integration hold promise for clinical and educational applications. Full article

The development of sustainable and functional nanocomposites has attracted considerable attention in recent years due to their broad spectrum of potential applications, including wood preservation. Also, a global goal is to reuse the large volumes of waste for environmental issues. In this context, the aim of the study was to obtain soda lignin particles, to graft ZnO nanoparticles onto their surface and to apply these hybrids, embedded into a biodegradable polymer matrix, as protection/preservation coating for oak wood. The organic–inorganic hybrids were characterized in terms of compositional, structural, thermal, and morphological properties that confirm the efficacy of soda lignin extraction and ZnO grafting by physical adsorption onto the decorating support and by weak interactions and coordination bonding between the components. The developed solution based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and lignin-ZnO was applied to oak wood specimens by brushing, and the improvement in hydrophobicity (evaluated by water absorption that decreased by 48.8% more than wood, humidity tests where the treated sample had a humidity of 4.734% in comparison with 34.911% for control, and contact angle of 97.8° vs. 80.5° for untreated wood) and UV and fungal attack protection, while maintaining the color and aspect of specimens, was sustained. L.ZnO are well dispersed into the polymer matrix, ensuring a smooth and less porous wood surface. According to the results, the obtained wood coating using both a biodegradable polymeric matrix and a waste-based preservative can be applied for protection against weathering degradation factors, with limited water uptake and swelling of the wood, UV shielding, reduced wood discoloration and photo-degradation, effective protection against fungi, and esthetic quality. Full article

RNA viruses pose significant threats to global health, causing diseases such as COVID-19, HIV/AIDS, influenza, and dengue. These viruses are characterized by high mutation rates, rapid evolution, and the ability to evade traditional antiviral therapies, making effective treatment and prevention particularly challenging. In recent years, CRISPR/Cas13 has emerged as a promising antiviral tool due to its ability to specifically target and degrade viral RNA. Unlike conventional antiviral strategies, Cas13 functions at the RNA level, providing a broad-spectrum and programmable approach to combating RNA viruses. Its flexibility allows for rapid adaptation of guide RNAs to counteract emerging viral variants, making it particularly suitable for highly diverse viruses such as SARS-CoV-2 and HIV. This review discusses up-to-date applications of Cas13 in targeting a wide range of RNA viruses, including SARS-CoV-2, HIV, dengue, influenza, and other RNA viruses, focusing on its therapeutic potential. Preclinical studies have demonstrated Cas13’s efficacy in degrading viral RNA and inhibiting replication, with applications spanning prophylactic interventions to post-infection treatments. However, challenges such as collateral cleavage, inefficient delivery, potential immunogenicity, and the development of an appropriate ethical framework must be addressed before clinical translation. Future research should focus on optimizing crRNA design, improving delivery systems, and conducting rigorous preclinical evaluations to enhance specificity, safety, and therapeutic efficacy. With continued advancements, Cas13 holds great promise as a revolutionary antiviral strategy, offering novel solutions to combat some of the world’s most persistent viral threats. Full article

Sporadic colorectal cancer (CRC), the third leading cause of cancer-related death globally, arises through a continuum from normal tissue to adenomas, progressing from low-grade (LGD) to high-grade dysplasia (HGD); yet, the early epigenetic drivers of this transition remain unclear. To investigate these events, we profiled LGD and HGD adenomas using EM-seq, and identified a consensus differential methylation signature (DMS) of 626 regions through two independent bioinformatics pipelines. This signature effectively distinguished LGD from HGD in both tissue and plasma-derived cell-free DNA (cfDNA), highlighting specific methylation patterns. Functional annotation indicated enrichment for regulatory elements associated with transcription factor activity and cell signaling. Applying the DMS to the TCGA CRC dataset revealed three tumor subtypes with increasing hypermethylation and one normal cluster. The most hypermethylated subtype exhibited poor survival, high mutation burden, and disrupted transcriptional networks. While overlapping with classical CpG Island Methylator Phenotype (CIMP) categories, the DMS captured a broader spectrum of methylation alterations. These findings suggest that the DMS captures functionally relevant, antecedent epigenetic alterations in CRC progression, enabling the robust stratification of dysplasia severity and tumor subtypes. This signature holds promise for enhancing preclinical detection and molecular classification, and warrants further evaluation in larger prospective cohorts. Full article

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. Cefmetazole (CMZ) and flomoxef (FMOX) are parenteral antibiotics that are widely used in Japan and have emerged as potential carbapenem alternatives. Repositioning these agents effectively addresses the clinical need for carbapenem-sparing strategies and outpatient ESBL-E management. This review aims to reposition CMZ and FMOX for real-world clinical practice by synthesizing basic research, clinical studies, and pharmacokinetics/pharmacodynamics (PKs/PDs) analyses, which suggest that these agents may be effective in treating ESBL-E infections—particularly urinary tract infections, as evidenced by their minimum inhibitory concentration (MIC) values. The clinical outcomes of these interventions have been comparable to those of carbapenems, which support their role in antimicrobial stewardship. Their PK/PD characteristics emphasize the importance of dose optimization to ensure therapeutic efficacy, whereas recent insights into resistance mechanisms provide a foundation for appropriate use. As novel antibiotic development takes substantial time, revisiting existing options is increasingly important. Notably, the Infectious Diseases Society of America’s 2024 guidance on antimicrobial resistance has omitted CMZ and FMOX, owing to which clinicians have limited guidance on their use, particularly in regions like Japan where these antibiotics are widely employed. By addressing this knowledge gap, the present review offers a comprehensive evaluation of these drugs and highlights their potential as intravenous agents in ESBL-E management. Furthermore, it highlights the ongoing challenge of ensuring effective oral step-down therapy in an outpatient setting to reinforce the global relevance of CMZ and FMOX in a broader treatment framework, underscoring their potential for outpatient administration where clinically appropriate. Full article

In this study, we study the trapping of linear water waves by infinite arrays of three-dimensional fixed periodic structures in a three-layer fluid. Each layer has an independent uniform velocity field with respect to the fixed ground in addition to the internal modes along the interfaces between layers. Dynamical stability between velocity shear and gravitational pull constrains the layer velocities to a neighbourhood of the diagonal $U_1=U_2=U_3$ in velocity space. A non-linear spectral problem results from the variational formulation. This problem can be linearized, resulting in a geometric condition (from energy minimization) that ensures the existence of trapped modes within the limits set by stability. These modes are solutions living the discrete spectrum that do not radiate energy to infinity. Symmetries reduce the global problem to solutions in the first octant of the three-dimensional velocity space. Examples are shown of configurations of obstacles which satisfy the stability and geometric conditions, depending on the values of the layer velocities. The robustness of the result of the vertical column from previous studies is confirmed in the new configurations. This allows for comparison principles (Cavalieri’s principle, etc.) to be used in determining whether trapped modes are generated. Full article

Alphaviruses engage a diverse array of attachment factors and receptors during viral entry, resulting in a broad host range and disease spectrum, and thus presenting them as a major global public health concern. The development of effective antivirals against these arboviruses relies on a comprehensive understanding of the molecular interplay between these viruses and host cell factors, as well as the wide range of immune responses that ensue following viral infection. In this review, we present the current understanding of the complex landscape of alphavirus interaction with attachment factors and entry receptors, some of which are characterized structurally, while others are characterized biochemically. Additionally, we provide an overview of the molecular bases of epitope recognition by neutralizing and non-neutralizing antibodies against alphaviruses, and how icosahedral symmetry influences these interactions, such as occupancy and neutralization potency. We further discuss the structural bases of epitope recognition of a few pan-alphavirus antibodies, their potential therapeutic implications, and offer future perspectives on the development of effective therapeutics against clinically relevant alphaviruses. Full article

Ancient grains, including wild rice, millet, fonio, teff, quinoa, amaranth, and sorghum, are re-emerging as vital components of modern diets due to their dense nutritional profiles and diverse health-promoting bioactive compounds. Rich in high-quality proteins, dietary fiber, essential micronutrients, and a broad spectrum of bioactive compounds such as phenolic acids, flavonoids, carotenoids, phytosterols, and betalains, these grains exhibit antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and immunomodulatory properties. Their health-promoting effects are underpinned by multiple interconnected mechanisms, including the reduction in oxidative stress, modulation of inflammatory pathways, regulation of glucose and lipid metabolism, support for mitochondrial function, and enhancement of gut microbiota composition. This review provides a comprehensive synthesis of the essential nutrients, phytochemicals, and functional properties of ancient grains, with particular emphasis on the nutritional and molecular mechanisms through which they contribute to the prevention and management of chronic diseases such as cardiovascular disease, type 2 diabetes, obesity, and metabolic syndrome. Additionally, it highlights the growing application of ancient grains in functional foods and nutrition-sensitive dietary strategies, alongside the technological, agronomic, and consumer-related challenges limiting their broader adoption. Future research priorities include well-designed human clinical trials, standardization of compositional data, innovations in processing for nutrient retention, and sustainable cultivation to fully harness the health, environmental, and cultural benefits of ancient grains within global food systems. Full article