Search Results (300)

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Leukemias and lymphomas are hematologic malignancies characterized by complex pathophysiological mechanisms and increasing global incidence. Despite advances in chemotherapy, immunotherapy, and targeted therapies, challenges such as drug resistance and relapse persist, necessitating novel therapeutic strategies. This review explores the cytotoxic potential of venoms derived from snakes, bees, and scorpions against leukemia and lymphoma cells. Numerous venom-derived components, such as L-amino acid oxidases (LAAOs), phospholipases A₂ (PLA₂s), and peptides like melittin, demonstrate selective antitumor activity through mechanisms involving oxidative stress, apoptosis induction, cell cycle arrest, and immunomodulation. These molecules exert their effects via mitochondrial pathways, caspase activation, and inhibition of pro-survival signaling cascades such as NF-κB and PI3K/Akt. Despite promising preclinical results, the clinical translation of these bioactive compounds remains limited due to challenges in standardization, delivery, and safety profiling. This review highlights recent advances in venom research, summarizes key molecular targets, and discusses future directions to harness venom-derived molecules as innovative therapies for hematological cancers. Full article

Scaffold architecture plays a significant role in regulating cellular and microbial interactions in tissue engineering applications. This study evaluates the performance of 3D-printed poly (lactic acid) (PLA) scaffolds with varying porosity levels (20%, 40%, 60%, 80%, and 100%) in mechanical strength, supporting human skin fibroblast (HSF) viability and reducing bacterial colonization of Gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus), and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli). The maximum tensile strength (28 MPa) was achieved in the 100% dense scaffold. Increasing porosity drastically decreased tensile strength, where 80% PLA scaffold possessed 16 MPa strength. At greater levels of porosity (60% and 40%), tensile strengths greatly decrease (8 MPa and 4 MPa), while ductility increases, especially at high porosity levels. HSF viability, assessed using the AlamarBlue assay, showed a time-dependent increase in cell proliferation, with the highest viability observed on scaffolds with 60% and 80% porosity. SEM imaging confirmed strong cell adhesion on the 80% porous scaffold, indicating that intermediate-to-high porosity enhances cell attachment and metabolic activity. In contrast, bacterial adhesion showed species-specific responses to scaffold porosity. S. epidermidis and E. coli exhibited a progressive increase in adherence with porosity, peaking at 100%. P. aeruginosa showed maximum adhesion at 80%, suggesting a porosity “sweet spot” that favors its colonization. S. aureus adhered most strongly to scaffolds with intermediate porosities (40–60%) and significantly less at 100% porosity. The current study provides insights into scaffold design considerations, emphasizing the need for optimized scaffold architecture that balances regenerative potential with infection control in tissue engineering applications. Full article

Microplastics and invasive species, driven by anthropogenic activities, significantly disrupt ecosystems and microbial communities. This study investigated the interactive effects of biodegradable microplastics (polylactic acid, or PLA, and polyhydroxyalkanoates, or PHAs) and the fungal pathogen Rhizoctonia solani on the invasive plant Solidago canadensis. One plant of Solidago canadensis/pot was cultivated in forest soil amended with 1% (w/w) microplastics and/or R. solani. PLA exhibited greater toxicity than PHAs, reducing the plant height, root length, and biomass by 68%, 44%, and 70%, respectively. Microplastics impaired the maximum quantum yield of photosystem II more severely than R. solani. However, S. canadensis demonstrated adaptive antioxidative and extracellular enzymatic mechanisms under combined stresses. A heatmap analysis revealed a positive correlation between PHAs and plant growth traits, while a redundancy analysis explained the 15.96% and 4.19% variability for the first two components (r² = 0.95). A structural equation model indicated the negative effects of morphology and physiology on biomass (β = −1.694 and β = −0.932; p < 0.001), countered by positive antioxidant contributions (β = 1.296; p < 0.001). These findings highlight complex interactions among microplastics, pathogens, and invasive species, offering insights into ecological management strategies under dual environmental pressures. Future studies should assess the long-term field effects and microbial mediation of these interactions. Full article

Batteries are used as energy storage devices in various equipment. Today, research is focused on solid-state batteries (SSBs), replacing the liquid electrolyte with a solid separator. The solid separators provide electrolyte stability, no leakage, and provide mechanical strength to the battery. Separators are mostly manufactured by either traditional processes or 3D printing technologies. These processes involve making a slurry of plastic, active and conductive material and usually adding a plasticizer when making thin films or filaments for 3D printing. This study investigates the additive manufacturing of solid-state electrolytes (SSEs) by employing fused deposition modeling (FDM) with recyclable, bio-derived polylactic acid (PLA) filaments. Precise control of macro-porosity is achieved by systematically varying key process parameters, including raster orientation, infill percentage, and interlayer adhesion conditions, thereby enabling the formation of tunable, interconnected pore networks within the polymer matrix. Following 3D printing, these engineered porous frameworks are infiltrated with lithium hexafluorophosphate (LiPF₆), which functions as the active ionic conductor. A tailored thermal sintering protocol is then applied to promote solid-phase fusion of the embedded salt throughout the macro-porous PLA scaffold, resulting in a mechanically robust and ionically conductive composite separator. The electrochemical ionic conductivity and structural integrity of the sintered SSEs are characterized through electrochemical impedance spectroscopy (EIS) and standardized mechanical testing to assess their suitability for integration into advanced solid-state battery architectures. The solid-state separator achieved an average ionic conductivity of 2.529 × 10⁻⁵ S·cm⁻¹. The integrated FDM-sintering process enhances ion exchange at the electrode–electrolyte interface, minimizes material waste, and supports cost-efficient, fully recyclable component fabrication. Full article

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that severely impacts patients’ quality of life. Although current therapies have improved symptom management, they often fail to alter disease progression and are associated with immunosuppressive side effects. This study evaluated the immunomodulatory potential of resolvin D2 (RvD2), a pro-resolving lipid mediator, using a murine model of colitis and the ex vivo treatment of intestinal mucosal biopsies from CD patients, comparing its effects to those of conventional anti-TNFα therapy. To determine the optimal concentration of RvD2 for application in human tissue explant cultures, an initial in vitro assay was conducted using intestinal biopsies from mice with experimentally induced colitis. The explants were treated in vitro with varying concentrations of RvD2, and 0.1 μM emerged as an effective dose. This concentration significantly reduced the transcriptional levels of TNF-α (p = 0.004) and IL-6 (p = 0.026). Intestinal mucosal biopsies from fifteen patients with CD and seven control individuals were analyzed to validate RNA-sequencing data, which revealed dysregulation in the RvD2 biosynthetic and signaling pathways. The real-time PCR confirmed an increased expression of PLA2G7 (p = 0.02) and ALOX15 (p = 0.02), while the immunohistochemical analysis demonstrated the reduced expression of the RvD2 receptor GPR18 (p = 0.04) in intestinal tissues from CD patients. Subsequently, samples from eight patients with active Crohn’s disease, eight patients in remission, and six healthy controls were used for the serum analysis of RvD2 by ELISA, in vitro treatment of intestinal biopsies with RvD2 or anti-TNF, followed by transcriptional analysis, and a multiplex assay of the explant culture supernatants. The serum analysis demonstrated elevated RvD2 levels in CD patients both with active disease (p = 0.02) and in remission (p = 0.002) compared to healthy controls. The ex vivo treatment of intestinal biopsies with RvD2 decreased IL1β (p = 0.04) and TNFα (p = 0.02) transcriptional levels, comparable to anti-TNFα therapy. Additionally, multiplex cytokine profiling confirmed a reduction in pro-inflammatory cytokines, including IL-6 (p = 0.01), IL-21 (p = 0.04), and IL-22 (p = 0.009), in the supernatant of samples treated with RvD2. Altogether, these findings suggest that RvD2 promotes the resolution of inflammation in CD and supports its potential as a promising therapeutic strategy. Full article

An experimental model of acute pulmonary damage was developed based on the intravenous injection of the phospholipase A₂ (PLA₂)-rich venom of Pseudechis papuanus (Papuan black snake) in mice. Venom caused pulmonary edema, with the accumulation of a protein-rich exudate, as observed histologically and by analysis of bronchoalveolar lavage fluid (BALF). In parallel, venom induced an increase in all of the pulmonary mechanical parameters evaluated, without causing major effects in terms of tracheal and bronchial reactivity. These effects were abrogated by incubating the venom with the PLA₂ inhibitor varespladib, indicating that this hydrolytic enzyme is responsible for these alterations. The venom was cytotoxic to endothelial cells in culture, hydrolyzed phospholipids of a pulmonary surfactant, and reduced the activity of angiotensin-converting enzyme in the lungs. The pretreatment of mice with the nitric oxide synthase inhibitor L-NAME reduced the protein concentration in the BALF, whereas no effect was observed when mice were pretreated with inhibitors of cyclooxygenase (COX), tumor necrosis factor-α (TNF-α), bradykinin, or neutrophils. Based on these findings, it is proposed that the rapid pathological effect of this venom in the lungs is mediated by (a) the direct cytotoxicity of venom PLA₂ on cells of the capillary–alveolar barrier, (b) the degradation of surfactant factor by PLA₂, (c) the deleterious action of nitric oxide in pulmonary tissue, and (d) the cytotoxic action of free hemoglobin that accumulates in the lungs as a consequence of venom-induced intravascular hemolysis. Our findings offer clues on the mechanisms of pathophysiological alterations induced by PLA₂s in a variety of pulmonary diseases, including acute respiratory distress syndrome (ARDS). Full article

Low-energy bone fractures refer to injuries that occur from minimal trauma or impact. These fractures are often a result of activities, such as falls from standing height or minor accidents, where the force exerted on the bone is insufficient to cause a break under normal conditions. To design an effective orthotic splint, it is critical to select the appropriate material that mimics the mechanical properties of traditional materials like plaster, which has long been used for immobilization purposes. In this case, Ansys CES Edupack 2025 software was utilized to evaluate and identify materials with mechanical characteristics similar to those of plaster. The software provided a list of six materials that met these criteria, but selecting the most suitable material involved more than just mechanical properties. Three different multicriteria decision-making methods were employed to ensure the best choice: TOPSIS, VIKOR, and COPRAS. These methods were applied to consider various factors, such as strength, flexibility, weight, cost, and ease of manufacturing. The results of the analyses revealed a strong consensus across all three methods. Each approach identified PLA (Polylactic Acid) as the most appropriate material for the orthotic design. Following the material selection process, simulations were conducted to assess the structural performance of the orthotic splint. The results determined that the minimum thickness required for the PLA orthosis was 4 mm, ensuring that it met all necessary criteria for acceptable stresses and deformations during the four primary movements exerted by the wrist. This thickness was sufficient to maintain the orthosis’s functionality without compromising comfort or effectiveness. Moreover, a significant improvement in the design was achieved through topological optimization, where the mass of the preliminary design was reduced by 9.58%, demonstrating an efficient use of material while maintaining structural integrity. Full article

Gibberella root rot (GRR), caused by Fusarium graminearum, is one of the major threats to maize production. However, the mechanism underlying maize’s response to GRR is not fully understood. Multi-omics study incorporating metabolomics reveals insights into maize–pathogen interactions. Using metabolomics and mass spectrometry imaging (MSI), maize inbred lines with GRR resistance (W438) and susceptibility (335M) were deployed to characterize specific metabolites associated with GRR. Analysis of significantly altered metabolites suggested that glycerophospholipid metabolism was highly associated with GRR resistance or susceptibility. Furthermore, the distinct accumulation of lysophosphatidylethanolamine (lysoPE) and lysophosphatidylcholine (lysoPC) from glycerophospholipid metabolism, along with the significant up-regulation of phospholipase (PLA) gene in the susceptible line, suggested that high levels of lysoPC and lysoPE contributed to GRR susceptibility. Meanwhile, genes encoding lysophospholipase (LPLA), the detoxification enzymes of lysoPC, were significantly activated in both genotypes. However, the significantly higher expression of LPLAs in the resistant line corresponded to a significant increase in the content of non-toxic sn-glycero-3-phosphocholine, whereas this increase was not observed in the susceptible line. MSI analysis revealed the involvement of other potential phospholipids in GRR susceptibility. Taken together, maintaining an appropriate concentration of lysophospholipids is crucial for their role in the signaling pathway that triggers GRR resistance without causing damage to maize roots. Full article

Almond peel extracts, containing 0.2–0.8% (w/w) phenolic compounds with notable antioxidant and antimicrobial activities, could be used as a natural source of active compounds for the development of active films for food preservation. In this study, almond peel extracts obtained by subcritical water extraction at 160 and 180 °C were incorporated into PLA films (PLA-E160 and PLA-E180). The films were characterized in terms of their microstructure, mechanical, barrier, optical and thermal properties. Furthermore, the release of phenolic compounds and hydroximethylfurfural (HFM) into food simulants with different polarity was evaluated, as well as the film’s potential antioxidant and antimicrobial activities. To validate their effectiveness as active packaging materials, shelf-life studies were conducted on fresh orange juice and sunflower oil packaged using PLA-160 films. The results show that the incorporation of the almond peel extracts led to significant changes in the films’ microstructure and mechanical properties, which became darker, mechanically less resistant, and stretchable (p < 0.05), with slightly lower thermal stability than neat PLA films. The release of phenolic compounds and HFM from extract-enriched films was promoted in the 95% ethanol simulant due to the matrix swelling and relaxation. Food products packaged with PLA-E160 exhibited slower oxidative degradation during storage, as indicated by the higher ascorbic acid content and hue color in orange juice and lower peroxide content in sunflower oil. Nevertheless, both in vivo and in vitro studies showed no antimicrobial effectiveness from the films, likely due to the limited release of active compounds to the surrounding medium. Thus, almond peel extract conferred valuable properties to PLA films, effectively reducing oxidative reactions in food products sensitive to these deterioration processes. Full article

Obtaining active extracts from beet root leaves and stems (BLS) is an alternative for the valorization of this agricultural waste. Subcritical water extraction (SWE) at 150 °C and 170 °C has been used to obtain these extracts, which were incorporated (6% wt.) into polymer matrices to produce antioxidant films of thermoplastic starch (TPS) and polylactic acid (PLA) for the preservation of sunflower oil. A high extraction yield (67–60% solubilized solids) was achieved, and the extracts contained high levels of total phenols (51–73 mg GAE·g⁻¹ extract) and betalains and great radical scavenging capacity (EC₅₀: 30–22 mg mg⁻¹ DPPH). The highest temperature promoted the extract’s phenolic richness and antioxidant capacity. The TPS and PLA films containing extracts exhibited color and UV-light blocking effects. The extracts reduced the oxygen permeability (OP) and water vapor permeability of PLA films while promoting those of the TPS films. The capacity of the films to preserve sunflower oil from oxidation was mainly controlled by the OP values of the films, which were very high in TPS films with low OP values. However, in the PLA films (which were more permeable to oxygen), the antioxidant extracts provided significant protection against sunflower oil oxidation. Full article

Biochar, an eco-friendly soil amendment, holds promise for remediating contaminated soils, yet its impacts on coastal wetland soils under combined microplastic (MP) and heavy metal (HM) pollution remain underexplored. This study examined the efficacy of 2% Spartina alterniflora-derived biochar (BC) in rehabilitating soils co-contaminated with cadmium (Cd) and two MPs—polyethylene (PE) and polylactic acid (PLA)—at 0.2% and 2% (w/w). The results indicated that biochar significantly elevated soil pH (8.35–8.43) and restored electrical conductivity (EC) to near-control levels, while enhancing organic matter content (up to 130% in PLA-contaminated soils), nutrient availability (e.g., phosphorus, potassium), and enzyme activity. Biochar reduced bioavailable Cd by 14–15% through adsorption and ion exchange. Although bacterial richness and diversity slightly declined, biochar reshaped microbial communities, enriching taxa linked to pollutant degradation (e.g., Proteobacteria, Bacteroidota) and upregulated functional genes associated with carbon, nitrogen, and sulfur cycling. Additionally, biochar boosted Suaeda salsa (S. salsa) biomass (e.g., 0.72 g/plant in A1B) and height (e.g., 14.07 cm in E1B) while reducing Cd accumulation (29.45% in shoots) and translocation. Remediation efficiency was most pronounced in soils with 0.2% PLA. These findings bridge critical knowledge gaps in biochar’s role in complexly polluted coastal wetlands and validate its potential for sustainable soil restoration. Full article

Background/Objectives. Central nervous system (CNS)-related diseases such as Alzheimer’s and Parkinson’s, Attention Deficit Hyperactive Disorder (ADHD), stroke, epilepsy, and migraines are leading causes of morbidity and disability worldwide. New solutions for drug delivery are increasingly needed. In this context, three-dimensional (3D) printing technology has introduced innovative alternatives to produce more efficient medicines with diverse features, patterns, and consistencies, particularly oral medications. Even though research in this area is growing rapidly, no study has thoroughly analyzed 3D printing oral drug delivery progress for the CNS. To fill this gap this study pursues to determine a technological landscape in this field. Methods. For this aim, a Competitive Technology Intelligence (CTI) methodology was applied, examining 747 publications from 1 January 2019 to 20 May 2024 published in the Scopus database. Results. The main advances identified comprise six categories: 3D printing techniques, characteristics and applications, materials, design factors, user acceptance, and quality processes. FDM was identified as the main technique for pharmaceutical use. The main applications include pills, polypills, caplets, gel caps, multitablets, orodispersible films, and tablets, featuring external patterns and internal structures with one or more active substances. Insights show that the most utilized materials are thermoplastic polymers like PLA, PVA, PCL, ABS, and HIPS. A novel design factor involves release patterns using compartments of varying thicknesses and volumes in the core. Additionally, advances in specialized software have enabled the creation of highly complex designs. In the user acceptance category, oral drugs dosages are tailored to the specific needs and preferences of neurological patients. Finally, for the quality aspect, the precision in Active Pharmaceutical Ingredient (API) dosage and controlled-release mechanisms are critical, given the narrow margin between therapeutic doses and toxicity for CNS diseases. Conclusions. Revealing these advancements in 3D printing for oral drug delivery allows researchers, academics, and decision-makers to identify opportunities and allocate resources efficiently, promising enhanced oral medicaments for the health and well-being of individuals suffering from CNS disorders. Full article

To address the limitations of poly (lactic acid) (PLA), it was blended with poly (methyl methacrylate) (PMMA) as a toughening component, using MgO nanoparticles (NPs, 0.075–0.15 wt%) as a catalyst. SEM pictures confirmed the good miscibility of the blends. Mechanical tests showed a slight decrease in elastic modulus and tensile strength for the PLA/PMMA125 sample containing 0.125% MgO. Yet, elongation at break rose by over 60% and impact strength increased by over 400% compared to pure PLA. Also, MgO facilitated the shifting of the glass transition temperature (T_g) of both polymers in DSC curves. Additionally, the absence of cold crystallization in PLA, coupled with reductions in its melting temperature (T_m) and crystallinity, were identified as critical factors contributing to improved miscibility within the reactive blend. Melt flow index (MFI) evaluation indicated a decrease in viscosity, while water contact angle measurements revealed an increase in polar groups on the surfaces of the MgO-containing samples. X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses confirmed the effective distribution and dispersion of NPs throughout the blend, along with a significant decrease in crystallinity. Moreover, DFT calculations were performed to better understand the role of MgO in the reaction. The findings offered key insights into the reaction mechanism, confirming that MgO plays a crucial role in facilitating the transesterification between PLA and PMMA. These findings underscore the enhanced performance of exchange reactions between the active groups of both polymers in the presence of MgO, leading to the formation of PLA-PMMA copolymers with superior miscibility and mechanical properties. Finally, a cell culture assay confirmed the blend’s non-toxicity, showing its versatile potential. Full article

Conventional techniques for incorporating active ingredients into polymeric matrices are accompanied by certain disadvantages, primarily attributable to the inherent characteristics of the active ingredient itself, including its sensitivity to temperature. A potential solution to these challenges lies in the utilization of supercritical carbon dioxide (scCO₂) for the formation of polymeric foam and the incorporation of active ingredients, in conjunction with the encapsulation of inclusion complexes (ICs), to ensure physical stability and augmented bioactivity. The objective of this study was to assess the impact of IC impregnation and subsequent foam formation on PLA films and PLA/PBAT blends that had been previously impregnated. The study’s methodology encompassed the formation and characterization of ICs with caffeic acid (CA) and β-cyclodextrin (β-CD), along with the thermal, structural, and morphological properties of the resulting materials. Higher incorporation of impregnated IC into the PLA(42)/PBAT(58) blend was observed at 12 MPa pressure and a depressurization rate of 1 MPa/min. The presence of IC, in addition to a lower rate of expansion, contributed to the formation of homogeneous cells with a size range of 4–44 um. On the other hand, the incorporation of IC caused a decrease in the crystallinity of the PLA fraction due to the interaction of the complex with the polymer. This study makes a significant contribution to the advancement of knowledge on the incorporation of compounds encapsulated in β-CD by scCO₂, as well as to the development of active materials with potential applications in food packaging. Full article