Search Results (55)

Cyclotides are exceptionally stable plant peptides whose biological activity is widely attributed to interactions with lipid membranes, yet the molecular mechanisms underlying these interactions remain incompletely resolved. Here, we employ microsecond-scale (1 μs) all-atom molecular dynamics simulations to investigate the membrane association of the cyclotide kalata B1 with phospholipid bilayers of distinct headgroup composition, including POPC, POPE, and POPG. This extended timescale enables full bilayer equilibration and allows observation of slower peptide-induced membrane responses that are not accessible in shorter simulations. Across all systems, kalata B1 rapidly adsorbs to the membrane surface and remains predominantly surface-associated throughout the simulations, while the cyclic cystine knot motif remains structurally intact, confirming the exceptional robustness of the cyclotide fold during membrane engagement. Lipid-dependent differences arise primarily from variations in peptide orientation, conformational flexibility, and interfacial dynamics rather than deep bilayer insertion or pore formation. Zwitterionic POPC membranes favor compact, upright peptide configurations, whereas POPE and POPG bilayers promote enhanced lateral spreading and dynamic reorganization driven by hydrogen bonding and electrostatic interactions, respectively. Leaflet-resolved analyses of lipid contacts, membrane thickness, and area per lipid reveal localized, asymmetric perturbations confined to the peptide-exposed leaflet, with no evidence of sustained bilayer thinning or global destabilization. Together, these results support an interfacial, headgroup-dependent mechanism of cyclotide membrane activity and reconcile previous experimental observations. This work provides molecular-level insight into lipid selectivity and early-stage cyclotide–membrane interactions that may inform future design of cyclotide-based bioactive agents. Full article

The present study investigates the surface integrity and flank wear of uncoated cermet inserts during dry turning of AISI 304 stainless steel. Three-dimensional metrology techniques were employed to assess both surface roughness and cutting-tool flank wear. Cutting speed and feed rate were the process parameters varied in the experiments. Both parameters exhibited a significant influence on the final surface quality. Specifically, increasing the cutting speed resulted in a deterioration of the surface finish under the evaluated conditions. Considering an average flank wear (VBB) of 0.1 mm as the tool life criterion, tool lives of 15 min and 9 min were achieved at cutting speeds of 120 m/min (lowest level) and 150 m/min (highest level), respectively. At lower cutting speeds, abrasive wear and adhesion were the predominant wear mechanisms, whereas chipping and diffusion became more pronounced at the higher cutting speed. The dry turning of AISI 304 stainless steel with uncoated cermet inserts proved viable in terms of sustainability and surface integrity; however, effective chip evacuation remains a critical concern. The use of compressed air or minimum quantity lubrication (MQL) may help mitigate this issue. Full article

A systematic review of the scientific literature focused on the analysis of the main strategies related to the management of Eichhornia crassipes [water hyacinth] in Mexico is presented. The review was classified according to the levels of the biomass valorization pyramid, using specific inclusion and exclusion criteria: (i) eradication; (ii) physical control of the plant; and (iii) exploitation of its biomass. It focused on research conducted in Mexico from 1971 to 2023, which allowed for the analysis of a total of 147 studies. The results indicated that 73.4% of the research in Mexico is oriented towards the exploitation and valorization of water hyacinth biomass through the transformation of the plant into mid-value products, such as chemicals and materials (70.7%), energy (12.2%), food (7.3%) and health and lifestyle products (9.8%); however the sectors considered high-added-value, such as pharmaceuticals, fine chemicals and food, continue to be areas of opportunity. The remaining 26.6% focuses on control and eradication strategies, through the insertion of biological enemies, and physical control, by means of cutting and crushing the plant in situ. This situation underscores the importance of promoting integrated management approaches that incorporate biomass recovery, contributing to environmental sustainability and the responsible use of this invasive resource. Full article

Menstruation, a biological phenomenon experienced by more than half of the global population, remains stigmatized and poorly addressed in the context of research and public discourse. One overlooked issue is that of “period pollution,” the waste generated by millions of feminine hygiene pads (menstrual pads) that end up in landfills or the environment. Simultaneously, Japanese knotweed (Reynoutria japonica), a non-native invasive plant which disrupts native species, leads to the disruption of ecological systems. This experimental study assesses the Japanese knotweed plant for its potential to serve as the absorbent core in a sustainable menstrual pad, helping to address both environmental challenges in tandem. As control groups, commercial pads (Natracare and Saathi) were tested for their performance as absorbent materials, as defined by the absorbency ratio (AR) test. All preliminary studies were done using normal saline solutions dyed with red food coloring. Saathi pads demonstrated significantly higher levels of AR compared to Natracare and knotweed pads due to the presence of superabsorbent polymers, making it an unreliable benchmark. Because Japanese knotweed is composed of cellulosic fibers that absorb water through hydrogen bonding to hydroxyl groups and capillary imbibition within porous fiber networks, lignin removal via alkaline processing was employed to enhance absorbency prior to experimental testing. The inner lumen of the knotweed was selected and delignified using a sodium hydroxide bath, later being shaped into an absorbent core akin to the measurements of the commercial pads and inserted into Natracare shells for proof-of-concept testing. Although knotweed-based pads exhibited lower AR values than Natracare, the testing places the knotweed prototype at approximately 40% of the fluid capacity, indicating a strong starting point for a natural fiber. To further evaluate the processing feasibility of Japanese knotweed beyond laboratory-scale pad prototyping, Japanese knotweed biomass was subjected to conventional Kraft pulping, which helps to remove lignin and increase absorbency. The Kraft pulping produced a moderately delignified brown pulp with a Kappa number of 20. Due to limiting factors, the absorbency of the pulp was not tested. However, the pulp’s fiber dimensions were comparable to hardwood pulps that are commonly used in absorbent applications, suggesting feasibility for future development into bleached fluff pulp and sustainable menstrual hygiene products. Full article

To enhance the sustainability of manufacturing, various clean cutting technologies have been developed, yet their sustainability assessment faces challenges in balancing multiple conflicting objectives and stakeholder interests. This paper proposes a game theory-based evaluation framework that treats environmental, technical, economic, and social dimensions as cooperative players. The Nash equilibrium model is employed to dynamically reconcile subjective weights from the analytic hierarchy process and objective weights from the entropy method, thus achieving optimal weight allocation. Experimental studies on Ti-6Al-4V titanium alloy milling compared dry milling, minimum quantity lubrication, and cryogenic minimum quantity lubrication (CMQL) under different parameters. Results demonstrate that the game-theoretic model effectively integrates preferences and achieves Nash equilibrium. CMQL showed superior performance, increasing tool life by approximately 40% and reducing surface roughness by about 25% compared to dry milling. Coated inserts reduced carbon emissions by nearly 30% versus end mills. The Nash equilibrium analysis demonstrates that dry milling with coated inserts attains the highest level of processing sustainability under high-speed conditions due to synergistic environmental and economic advantages, while simultaneously revealing practical trade-offs among competing objectives. This study confirms that the proposed framework enables scientific weight coordination and provides a quantifiable, interpretable decision-making system for sustainable process selection. Full article

Background/Objectives: Ocular drug delivery faces significant challenges due to anatomical and physiological barriers that limit drug bioavailability, particularly with conventional eye drops. Levofloxacin (LEVO), a broad-spectrum antibiotic, is widely used in the treatment of bacterial conjunctivitis, but its therapeutic efficacy is hindered by rapid precorneal clearance and short residence time. Methods: This study introduces a biorelevant 2 mL dissolution model to simulate ocular conditions better and evaluate the release kinetics of LEVO-loaded nanofibrous ophthalmic inserts. Compared to the conventional 40 mL setup, the 2 mL system demonstrated a slower and more sustained drug release profile, with kinetic modeling confirming a more controlled release behavior. Difference and similarity factor analysis further validated the distinct release profiles, highlighting the impact of dissolution volume on release dynamics. Results: Preliminary pharmacokinetic modeling suggested that the nanofiber inserts, particularly when applied twice daily, maintained levofloxacin concentrations above minimum inhibitory and bactericidal levels for extended durations across three bacterial strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), potentially outperforming traditional eye drops. Conclusions: These findings suggest that small-volume dissolution testing may provide a more realistic method for evaluating ophthalmic insert formulations, though in vivo validation is needed. Moreover, the nanofibrous inserts show potential as a sustained-release alternative that warrants further investigation to improve patient compliance and therapeutic outcomes in ocular disease management. Full article

With the increasing severity of forest pest problems, breeding insect-resistant varieties has become a crucial task for the sustainable development of forestry. The highly insect-resistant triploid Populus line Pb29, genetically modified with BtCry1Ac, served as the maternal parent in controlled hybridization with three paternal Populus cultivars. Hybrid progenies were obtained through embryo rescue and tissue culture. Results showed that 4 °C storage was favorable for pollen preservation, with 84K poplar exhibiting superior pollen viability and embryo germination rates. All progenies displayed significantly lower seedling height and ground diameter growth than the maternal parent (p < 0.05), with some showing leaf shape and branching variations. Among the three crosses, the 84K-sired progeny exhibited the best growth performance but the highest variability. PCR analysis confirmed stable inheritance of the BtCry1Ac and Kan genes from Pb29, showing tight linkage. Progenies carrying BtCry1Ac exhibited detectable gene transcription and toxic protein accumulation, though expression levels varied due to copy number, insertion sites, and potential co-suppression effects. Ploidy analysis suggested all hybrids were aneuploid, with lower survival rates than the maternal parent. Insect-feeding assays confirmed high resistance in all BtCry1Ac-inheriting progenies, with an average larval mortality rate of 97.03%. Mortality rates and death indices significantly correlated with transcript abundance and toxin protein levels. These results demonstrate that BtCry1Ac insect resistance is stably inherited through hybridization. Transgene expression appears co-modulated by copy number, insertion sites, and ploidy status. Simultaneously, it was found that the aneuploid progeny derived from triploid hybridization exhibited growth disadvantages. This provides an important basis for subsequent poplar improvement breeding. Full article

Considering the absence of a widely utilized EBV vaccine, we have developed an EBV gL-gH344-Ferritin nanoparticle vaccine utilizing ferritin as a carrier. The gL-gH344-Ferritin fusion gene was synthesized and inserted into the pET30a plasmid. The expression of the fusion protein in the recombinant plasmid was verified by Western blot. Then, the gL-gH344-Ferritin subunit nanoparticle vaccine was obtained by purification of the fusion protein. BALB/c mice were immunized using a two-dose protocol. The titers of EBV specific antibodies were determined using enzyme-linked immunosorbent assay at 4, 8, and 12 weeks after the initial immunization. Moreover, the levels of EBV gL-gH344 specific splenocytes secreting interferon (IFN)-γ and interleukin (IL)-6 were determined using an enzyme-linked immunospot assay. The pET30a-gL-gH344-Ferritin prokaryotic expression plasmid was successfully constructed. gL-gH344-Ferritin was efficiently expressed in E. coli. Following immunization with gL-gH344-Ferritin, the mice sera demonstrated elevated titers of EBV specific immunoglobulin G. Moreover, after stimulating with EBV gL-gH344 specific peptides, the splenocytes of the immunized mice showed a marked tendency to secrete large amounts of IFN-γ and IL-6. The gL-gH344-Ferritin nanoparticle vaccine carrying the EBV gL-gH344 fusion protein induced robust and sustained specific humoral and cellular immune responses in mice. Full article

Background/Objectives: Interleukin-1 (IL-1) is a pivotal mediator in the pathological progression of osteoarthritis (OA), playing a central role in disease progression. However, the rapid clearance of IL-1 receptor antagonist (IL-1Ra) from the joints may hinder the efficacy of intra-articular IL-1Ra injections in reducing OA-associated pain or cartilage degradation. Methods: Sustaining sufficient levels of IL-1Ra within the joints via adeno-associated virus (AAV)-mediated gene therapy presents a promising therapeutic strategy for OA. In this study, we constructed an IL-1Ra expression cassette employing intron insertion in the coding sequence (CDS) region to enhance protein expression levels. Furthermore, we incorporated precisely targeted liver-specific microRNA (miRNA) sequences to specifically downregulate transgene expression within hepatic tissues, thereby ensuring more targeted and controlled regulation of gene expression. Results: A rat model of OA was employed to compare the efficacy of AAV5 and AAV9 for IL-1Ra delivery at both high and low doses. It was observed that low-dose, but not high-dose, AAV9-IL-1Ra resulted in a significant reduction in joint swelling, accompanied by a decrease in the diameter of the affected area and the preservation of biomarkers associated with trabecular bone integrity. Conclusions: These results highlight the great potential of AAV9-IL-1Ra in osteoarthritis therapy, with the promise of achieving long-term improvement through a single intra-articular injection. Full article

Increasing environmental concerns and the need for sustainable materials have driven a focus towards the utilization of recycled polylactic acid (PLA) in additive manufacturing as PLA offers advantages over other thermoplastics, including biodegradability, ease of processing, and a lower environmental impact during production. This study explores the optimization of the mechanical properties of recycled PLA parts through a combination of experimental and machine learning approaches. A series of experiments were conducted to investigate the impact of various processing parameters, such as layer thickness and infill density, as well as annealing conditions, on the mechanical properties of recycled PLA parts. Machine learning algorithms have proven the possibility to predict tensile behavior with an average error of 6.059%. The results demonstrate that specific combinations of processing parameters and post-treatment annealing differently improve the mechanical properties (with 7.31% in ultimate tensile strength (UTS), 0.28% in Young’s modulus, and 3.68% in elongation) and crystallinity (with 22.33%) of recycled PLA according to XRD analysis, making it a viable alternative to virgin PLA in various applications such as sustainable packaging solutions, including biodegradable containers, clamshell packaging, and protective inserts. The optimized recycled PLA parts exhibited mechanical properties and crystallinity levels comparable to those of their virgin counterparts, highlighting their potential for reducing environmental impact and saving costs. For both as-built and annealed samples, the optimal settings for achieving high composite desirability involved a 0.2 mm layer thickness, with 75% infill for the as-built samples and 100% infill for the annealed samples. This study provides a comprehensive framework for optimizing recycled PLA in additive manufacturing, contributing to the advancement of sustainable material engineering and the circular economy. Full article

Background/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery. Methods: Indomethacin-loaded mixed micelles (IDM-MMs) were prepared from Soluplus^® and Poloxamer F127 by means of a thin-film hydration method. The MMs-loaded DMNs were fabricated using a two-step molding method and evaluated for storage stability, insertion ability, in vitro release, in vitro transdermal penetration, and in vivo PK/PD studies. Results: The obtained MMs were stable at 4 °C and 30 °C for 60 days. The in vitro IDM transdermal penetration was remarkably improved by the MMs-loaded DMNs compared to a commercial patch. A pharmacokinetic study demonstrated that the MMs-loaded DMNs had a relative bioavailability of 4.1 in comparison with the commercial patch. Furthermore, the MMs-loaded DMNs showed a significantly shorter lag time than the commercial patch, as well as a more stable plasma concentration than the DMNs without MMs. The therapeutic efficacy of the IDM DMNs was examined in Complete Freund’s Adjuvant-induced arthritis mice. The IDM DMN treatment effectively reduced arthritis severity, resulting in decreased paw swelling, arthritis index, spleen hyperplasia, and serum IL-1β and TNF-α levels. Conclusions: Our findings demonstrated that the novel MMs-loaded DMNs were an effective strategy for sustained IDM release, providing an alternate route of anti-inflammatory drug delivery. Full article

Honokiol, a biphenyl lignan extracted from bark extracts belonging to Magnolia plant species, is a pleiotropic compound which exhibits a widespread range of antioxidant, antibacterial, antidiabetic, anti-inflammatory, antiaggregant, analgesic, antitumor, antiviral and neuroprotective activities. Honokiol, being highly hydrophobic, is soluble in common organic solvents but insoluble in water. Therefore, its biological effects could depend on its bioactive mechanism. Although honokiol has many impressive bioactive properties, its effects are unknown at the level of the biological membrane. Understanding honokiol’s bioactive mechanism could unlock innovative perspectives for its therapeutic development or for therapeutic development of molecules similar to it. I have studied the behaviour of the honokiol molecule in the presence of a plasma-like membrane and established the detailed relation of honokiol with membrane components using all-atom molecular dynamics. The results obtained in this work sustain that honokiol has a tendency to insert inside the membrane; locates near and below the cholesterol oxygen atom, amid the hydrocarbon membrane palisade; increases slightly hydrocarbon fluidity; does not interact specifically with any membrane lipid; and, significantly, forms aggregates. Significantly, aggregation does not impede honokiol from going inside the membrane. Some of the biological characteristics of honokiol could be accredited to its aptitude to alter membrane biophysical properties, but the establishment of aggregate forms in solution might hamper its clinical use. Full article

Background: Exercise is associated with several cardiac adaptations that can enhance one’s cardiac output and allow one to sustain a higher level of oxygen demand for prolonged periods. However, adverse cardiac remodelling, such as myocardial fibrosis, has been identified in athletes engaging in long-term endurance exercise. Cardiac magnetic resonance (CMR) imaging is considered the noninvasive gold standard for its detection and quantification. This review seeks to highlight factors that contribute to the development of myocardial fibrosis in athletes and provide insights into the assessment and interpretation of myocardial fibrosis in athletes. Methods: A literature search was performed using the PubMed/Medline database and Google Scholar for publications that assessed myocardial fibrosis in athletes using CMR. Results: A total of 21 studies involving 1642 endurance athletes were included in the analysis, and myocardial fibrosis was found in 378 of 1595 athletes. A higher prevalence was seen in athletes with cardiac remodelling compared to control subjects (23.7 vs. 3.3%, p < 0.001). Similarly, we found that young endurance athletes had a significantly higher prevalence than veteran athletes (27.7 vs. 19.9%, p < 0.001), while male and female athletes were similar (19.7 vs. 16.4%, p = 0.207). Major myocardial fibrosis (nonischaemic and ischaemic patterns) was predominately observed in veteran athletes, particularly in males and infrequently in young athletes. The right ventricular insertion point was the most common fibrosis location, occurring in the majority of female (96%) and young athletes (84%). Myocardial native T1 values were significantly lower in athletes at 1.5 T (p < 0.001) and 3 T (p = 0.004), although they had similar extracellular volume values to those of control groups. Conclusions: The development of myocardial fibrosis in athletes appears to be a multifactorial process, with genetics, hormones, the exercise dose, and an adverse cardiovascular risk profile playing key roles. Major myocardial fibrosis is not a benign finding and warrants a comprehensive evaluation and follow-up regarding potential cardiac disease. Full article

Endothelial nitric oxide (NO) production is crucial in maintaining vascular homeostasis. However, in the context of ischemia–reperfusion (I/R) injury, uncoupled endothelial nitric oxide synthase (eNOS) can exacerbate reactive oxygen species (ROS) generation. Supplementation with S-nitroso human serum albumin (S-NO-HSA) offers a potential solution by mitigating eNOS uncoupling, thereby enhancing NO bioavailability. In a study conducted at the University of Verona, male rats underwent thoracotomy followed by 30 min left anterior descendant coronary (LAD) occlusion and subsequent reperfusion. Hemodynamic parameters were meticulously assessed using a conductance catheter inserted via the carotid artery. The rats were stratified into two main groups based on reperfusion duration and the timing of drug infusion, with the effects of S-NO-HSA evaluated after 2 or 24 h. Remarkably, intravenous administration of S-NO-HSA, initiated before or during ischemia, exhibited notable benefits. It significantly improved left ventricular function, safeguarded energetic substrates such as phosphocreatine and ATP, and sustained glutathione levels akin to basal conditions, indicative of diminished oxidative stress. The data from this study strongly suggest a protective role for S-NO-HSA in mitigating I/R injury induced by LAD artery occlusion, a phenomenon observed at both 2 and 24 h post-reperfusion. These findings underscore the promising therapeutic potential of NO supplementation in alleviating myocardial damage subsequent to ischemic insult. Full article

This paper focuses on traceability as a means to ensure sustainability during food development by using augmented reality and addressing the needs of farmers/producers, development and retail companies, and consumers. After reviewing related work, the needs are outlined for an application with a highly visual interface that lets all involved parties insert, explore, and view data about food products, starting from their origin and dietary/heritage value until their placement in a market. In this direction, the research questions examined the usability of such an application along with its validity concerning whether customers would choose healthy food products based on certain criteria, ensuring sustainability at all levels. Data are selected from predefined lists where possible and propagated without disruption from farmers to markets to avoid errors. The analysis led to the AR application, FoodTrace, whose design and prototype implementation are also presented. The evaluation was encouraging as the research goals were largely met regarding both usability and content value and will help further develop the application. Full article