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52 pages, 7563 KiB  
Article
Design and Evaluation of a Inonotus obliquus–AgNP–Maltodextrin Delivery System: Antioxidant, Antimicrobial, Acetylcholinesterase Inhibitory and Cytotoxic Potential
by Ana-Maria Stanoiu, Cornelia Bejenaru, Adina-Elena Segneanu, Gabriela Vlase, Ionela Amalia Bradu, Titus Vlase, George Dan Mogoşanu, Maria Viorica Ciocîlteu, Andrei Biţă, Roxana Kostici, Dumitru-Daniel Herea and Ludovic Everard Bejenaru
Polymers 2025, 17(15), 2163; https://doi.org/10.3390/polym17152163 (registering DOI) - 7 Aug 2025
Abstract
Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and [...] Read more.
Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and bioavailability of its bioactive constituents. Two distinct delivery systems were designed to enhance the functionality of I. obliquus extracts: (i) microencapsulation in maltodextrin (MIO) and (ii) a sequential approach involving preparation of silver nanoparticle-loaded I. obliquus (IO–AgNPs), followed by microencapsulation to yield the hybrid MIO–AgNP system. Comprehensive metabolite profiling using GC–MS and ESI–QTOF–MS revealed 142 bioactive constituents, including terpenoids, flavonoids, phenolic acids, amino acids, coumarins, styrylpyrones, fatty acids, and phytosterols. Structural integrity and successful encapsulation were confirmed by XRD, FTIR, and SEM analyses. Both IO–AgNPs and MIO–AgNPs demonstrated potent antioxidant activity, significant acetylcholinesterase inhibition, and robust antimicrobial effects against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli. Cytotoxicity assays revealed pronounced activity against MCF-7, HCT116, and HeLa cell lines, with MIO–AgNPs exhibiting superior efficacy. The synergistic integration of maltodextrin and AgNPs enhanced compound stability and bioactivity. As the first report on Romanian I. obliquus, this study highlights its therapeutic potential and establishes polymer-based nanoencapsulation as an effective strategy for optimizing its applications in combating microbial resistance and cancer. Full article
(This article belongs to the Section Polymer Applications)
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25 pages, 745 KiB  
Review
Design and Application of Superhydrophobic Magnetic Nanomaterials for Efficient Oil–Water Separation: A Critical Review
by Rabiga M. Kudaibergenova, Elvira A. Baibazarova, Didara T. Balpanova, Gulnar K. Sugurbekova, Aizhan M. Serikbayeva, Marzhan S. Kalmakhanova, Nazgul S. Murzakasymova, Arman A. Kabdushev and Seitzhan A. Orynbayev
Molecules 2025, 30(15), 3313; https://doi.org/10.3390/molecules30153313 (registering DOI) - 7 Aug 2025
Abstract
Superhydrophobic magnetic nanomaterials (SHMNMs) are emerging as multifunctional platforms for efficient oil–water separation due to their combination of extreme water repellency, strong oil affinity, and external magnetic responsiveness. This review presents a comprehensive analysis of recent advances in the design, synthesis, and environmental [...] Read more.
Superhydrophobic magnetic nanomaterials (SHMNMs) are emerging as multifunctional platforms for efficient oil–water separation due to their combination of extreme water repellency, strong oil affinity, and external magnetic responsiveness. This review presents a comprehensive analysis of recent advances in the design, synthesis, and environmental application of SHMNMs. The theoretical foundations of superhydrophobicity and the physicochemical behavior of magnetic nanoparticles are first outlined, followed by discussion of their synergistic integration. Key fabrication techniques—such as sol–gel synthesis, electrospinning, dip-coating, laser-assisted processing, and the use of biomass-derived precursors—are critically assessed in terms of their ability to tailor surface morphology, chemical functionality, and long-term durability. The review further explores the mechanisms of oil adsorption, magnetic separation, and material reusability under realistic environmental conditions. Special attention is paid to the scalability, mechanical resilience, and environmental compatibility of SHMNMs in the context of water treatment technologies. Current limitations, including reduced efficiency in harsh media, potential environmental risks, and challenges in material regeneration, are discussed. This work provides a structured overview that could support the rational development of next-generation superhydrophobic materials tailored for sustainable and high-performance separation of oil and organic pollutants from water. Full article
(This article belongs to the Special Issue Recent Advances in Superhydrophobic Materials and Their Application)
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20 pages, 1149 KiB  
Article
Assessment of Biomethane Potential from Waste Activated Sludge in Swine Wastewater Treatment and Its Co-Digestion with Swine Slurry, Water Lily, and Lotus
by Sartika Indah Amalia Sudiarto, Hong Lim Choi, Anriansyah Renggaman and Arumuganainar Suresh
AgriEngineering 2025, 7(8), 254; https://doi.org/10.3390/agriengineering7080254 (registering DOI) - 7 Aug 2025
Abstract
Waste activated sludge (WAS), a byproduct of livestock wastewater treatment, poses significant disposal challenges due to its low biodegradability and potential environmental impact. Anaerobic digestion (AD) offers a sustainable approach for methane recovery and sludge stabilization. This study evaluates the biomethane potential (BMP) [...] Read more.
Waste activated sludge (WAS), a byproduct of livestock wastewater treatment, poses significant disposal challenges due to its low biodegradability and potential environmental impact. Anaerobic digestion (AD) offers a sustainable approach for methane recovery and sludge stabilization. This study evaluates the biomethane potential (BMP) of WAS and its co-digestion with swine slurry (SS), water lily (Nymphaea spp.), and lotus (Nelumbo nucifera) shoot biomass to enhance methane yield. Batch BMP assays were conducted at substrate-to-inoculum (S/I) ratios of 1.0 and 0.5, with methane production kinetics analyzed using the modified Gompertz model. Mono-digestion of WAS yielded 259.35–460.88 NmL CH4/g VSadded, while co-digestion with SS, water lily, and lotus increased yields by 14.89%, 10.97%, and 16.89%, respectively, surpassing 500 NmL CH4/g VSadded. All co-digestion combinations exhibited synergistic effects (α > 1), enhancing methane production beyond individual substrate contributions. Lower S/I ratios improved methane yields and biodegradability, highlighting the role of inoculum availability. Co-digestion reduced the lag phase limitations of WAS and plant biomass, improving process efficiency. These findings demonstrate that co-digesting WAS with nutrient-rich co-substrates optimizes biogas production, supporting sustainable sludge management and renewable energy recovery in livestock wastewater treatment systems. Full article
(This article belongs to the Section Sustainable Bioresource and Bioprocess Engineering)
27 pages, 1680 KiB  
Review
Microtubule-Targeting Agents: Advances in Tubulin Binding and Small Molecule Therapy for Gliomas and Neurodegenerative Diseases
by Maya Ezzo and Sandrine Etienne-Manneville
Int. J. Mol. Sci. 2025, 26(15), 7652; https://doi.org/10.3390/ijms26157652 (registering DOI) - 7 Aug 2025
Abstract
Microtubules play a key role in cell division and cell migration. Thus, microtubule-targeting agents (MTAs) are pivotal in cancer therapy due to their ability to disrupt cell division microtubule dynamics. Traditionally divided into stabilizers and destabilizers, MTAs are increasingly being repurposed for central [...] Read more.
Microtubules play a key role in cell division and cell migration. Thus, microtubule-targeting agents (MTAs) are pivotal in cancer therapy due to their ability to disrupt cell division microtubule dynamics. Traditionally divided into stabilizers and destabilizers, MTAs are increasingly being repurposed for central nervous system (CNS) applications, including brain malignancies such as gliomas and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Microtubule-stabilizing agents, such as taxanes and epothilones, promote microtubule assembly and have shown efficacy in both tumour suppression and neuronal repair, though their CNS use is hindered by blood–brain barrier (BBB) permeability and neurotoxicity. Destabilizing agents, including colchicine-site and vinca domain binders, offer potent anticancer effects but pose greater risks for neuronal toxicity. This review highlights the mapping of nine distinct tubulin binding pockets—including classical (taxane, vinca, colchicine) and emerging (tumabulin, pironetin) sites—that offer new pharmacological entry points. We summarize the recent advances in structural biology and drug design, enabling MTAs to move beyond anti-mitotic roles, unlocking applications in both cancer and neurodegeneration for next-generation MTAs with enhanced specificity and BBB penetration. We further discuss the therapeutic potential of combination strategies, including MTAs with radiation, histone deacetylase (HDAC) inhibitors, or antibody–drug conjugates, that show synergistic effects in glioblastoma models. Furthermore, innovative delivery systems like nanoparticles and liposomes are enhancing CNS drug delivery. Overall, MTAs continue to evolve as multifunctional tools with expanding applications across oncology and neurology, with future therapies focusing on optimizing efficacy, reducing toxicity, and overcoming therapeutic resistance in brain-related diseases. Full article
(This article belongs to the Special Issue New Drugs Regulating Cytoskeletons in Human Health and Diseases)
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22 pages, 4651 KiB  
Review
Potential Issues and Optimization Solutions for High-Compression-Ratio Utilization in Hybrid-Dedicated Gasoline Engines
by Qiuyu Liu, Baitan Ma, Zhiqiang Zhang, Chunyun Fu and Zhe Kang
Energies 2025, 18(15), 4204; https://doi.org/10.3390/en18154204 (registering DOI) - 7 Aug 2025
Abstract
This systematic review critically examines the benefits and challenges of high-compression-ratio (CR) implementation in hybrid-dedicated engines, recognizing CR increase as a pivotal strategy for enhancing the indicated thermal efficiency to achieve carbon peak and carbon neutrality goals. However, excessively high CRs face critical [...] Read more.
This systematic review critically examines the benefits and challenges of high-compression-ratio (CR) implementation in hybrid-dedicated engines, recognizing CR increase as a pivotal strategy for enhancing the indicated thermal efficiency to achieve carbon peak and carbon neutrality goals. However, excessively high CRs face critical constraints, including intensified knock propensity, increased heat transfer (HTR) losses, reduced combustion stability, augmented dissociation losses, and cold-start misfire risks. The feasibility and necessity of CR enhancement in hybrid systems were comprehensively evaluated based on these factors, with fundamental mechanisms of the detrimental effects elucidated. To address these challenges, optimized countermeasures were synthesized: knock suppression via high-octane fuels, EGR technology, lean combustion, and in-cylinder water injection; heat transfer reduction through thermal barrier coatings and independent CR/expansion-ratio control; misfire risk monitoring using ion current or cylinder pressure sensors. These approaches provide viable pathways to overcome high-CR limitations and optimize engine performance. Nevertheless, current research remains confined to isolated solutions, warranting future focus on integrated optimization mechanisms investigating synergistic interactions of multiple strategies under high-CR conditions. Full article
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16 pages, 2855 KiB  
Article
Cysteine Surface Engineering of Green-Synthesized Gold Nanoparticles for Enhanced Antimicrobial and Antifungal Activity
by Karen M. Soto, Angelica Gódinez-Oviedo, Adriana Romo-Pérez, Sandra Mendoza, José Mauricio López-Romero, Gerardo Torres-Delgado, Jorge Pineda-Piñón, Luis M. Apátiga-Castro, José de Jesús Pérez Bueno and Alejandro Manzano-Ramírez
Int. J. Mol. Sci. 2025, 26(15), 7645; https://doi.org/10.3390/ijms26157645 - 7 Aug 2025
Abstract
Green synthesis of gold nanoparticles (AuNPs) provides a significantly eco-friendly and low-impact counterpart to conventional chemical methods. In the present study, we synthesized gold nanoparticles using Schinus molle (P-AuNPs) aqueous extract as a reducing and stabilizing agent. The obtained nanoparticles were then stabilized [...] Read more.
Green synthesis of gold nanoparticles (AuNPs) provides a significantly eco-friendly and low-impact counterpart to conventional chemical methods. In the present study, we synthesized gold nanoparticles using Schinus molle (P-AuNPs) aqueous extract as a reducing and stabilizing agent. The obtained nanoparticles were then stabilized by another biocompatible agent, the chiral amino acids L-cysteine (L-Cys-AuNPs) and D-cysteine (D-Cys-AuNPs), to estimate the potential of the surface modification for enhancing AuNPs surface chemistry and antimicrobial action. The synthesized gold nanoparticles were confirmed by UV-Vis spectroscopy, FTIR, XRD, and circular dichroism to validate their formation, crystalline structure, surface properties, and chirality. Physicochemical characterization confirmed the formation of crystalline AuNPs with size and morphology modulated by chiral functionalization. TEM and DLS analyses showed that L-cysteine-functionalized AuNPs were smaller and more uniform, while FTIR and circular dichroism spectroscopy confirmed surface binding and the induction of optical activity, respectively. L-Cys-AuNPs exhibited the highest antimicrobial efficacy against a broad spectrum of microorganisms, including Escherichia coli, Salmonella enterica, Listeria monocytogenes, Staphylococcus aureus, Staphylococcus epidermidis, and, notably, Candida albicans. L-Cys-AuNPs showed the lowest MIC and MBC values, highlighting the synergistic effect of chirality on biological performance. These findings suggest that L-cysteine surface engineering significantly enhances the therapeutic potential of AuNPs, particularly in combating drug-resistant fungal pathogens such as C. albicans. This research paves the way for the development of next-generation antimicrobial agents, reinforcing the relevance of green nanotechnology in the field of materials science and nanotechnology. Full article
(This article belongs to the Special Issue Antimicrobial Nanomaterials: Approaches, Strategies and Applications)
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20 pages, 3766 KiB  
Review
Challenges, Unmet Needs, and Future Directions for Nanocrystals in Dermal Drug Delivery
by Muzn Alkhaldi and Cornelia M. Keck
Molecules 2025, 30(15), 3308; https://doi.org/10.3390/molecules30153308 - 7 Aug 2025
Abstract
Nanocrystals, defined as crystalline particles with dimensions in the nanometer range (<1000 nm), exhibit unique properties that enhance the efficacy of poorly soluble active compounds. This review explores the fundamental aspects of nanocrystals, including their characteristics and various preparation methods, while addressing critical [...] Read more.
Nanocrystals, defined as crystalline particles with dimensions in the nanometer range (<1000 nm), exhibit unique properties that enhance the efficacy of poorly soluble active compounds. This review explores the fundamental aspects of nanocrystals, including their characteristics and various preparation methods, while addressing critical factors that influence their stability and incorporation into final products. A key focus of the review is the advantages offered by nanocrystals in dermal applications. It also highlights their ability to enhance passive diffusion into the skin and facilitate penetration via particle-assisted dermal penetration. Additionally, the review discusses their capacity to penetrate into hair follicles, enabling targeted drug delivery, and their synergistic potential when combined with microneedles, which further enhance the dermal absorption of active compounds. The review also addresses several commercial products that successfully employ nanocrystal technology, showcasing its practical applications. Summary: Nanocrystals with their special properties are an emerging trend for dermal applications, particularly the development of plantCrystals—natural nanocrystals sourced from plant materials—which represent a promising path for future research and formulation strategies. These advancements could lead to more sustainable and effective dermal products. Full article
(This article belongs to the Section Natural Products Chemistry)
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14 pages, 2763 KiB  
Review
Molecular Crosstalk Between RUNX2 and HIF-1α in Osteosarcoma: Implications for Angiogenesis, Metastasis, and Therapy Resistance
by Anuja Gajanan Magar, Vivek Kumar Morya and Kyu-Cheol Noh
Int. J. Mol. Sci. 2025, 26(15), 7642; https://doi.org/10.3390/ijms26157642 - 7 Aug 2025
Abstract
Runt-related transcription factor-2 (RUNX2) is an integral player in osteogenesis and is highly expressed in osteosarcoma. Emerging evidence suggests that aberrant RUNX2 expression is a key factor in osteosarcoma oncogenesis. Patients with advanced stages of osteosarcoma overexpressing RUNX2 are more likely to have [...] Read more.
Runt-related transcription factor-2 (RUNX2) is an integral player in osteogenesis and is highly expressed in osteosarcoma. Emerging evidence suggests that aberrant RUNX2 expression is a key factor in osteosarcoma oncogenesis. Patients with advanced stages of osteosarcoma overexpressing RUNX2 are more likely to have high tumour grades, metastasis, and lower overall or progression-free survival rates. Thus, RUNX2 is considered a potential candidate for targeted therapy of osteosarcoma. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor involved in the regulation of cellular reprogramming in response to hypoxia. Overexpression of HIF-1α decreases overall survival, disease-free survival, and chemotherapy response and promotes tumour stage and metastasis. Hence, our review focused on highlighting the intricate network between RUNX2 and HIF-1α, which support each other or may work synergistically to develop resistance to therapy and osteosarcoma progression. An in-depth understanding of these two important tumour progression markers is required. Therefore, this review focuses on the role of RUNX2 and HIF-1α in the alteration of the tumour microenvironment, which further promotes angiogenesis, metastasis, and resistance to therapy in osteosarcoma. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology, 3rd Edition)
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16 pages, 2159 KiB  
Article
A Comparison of eDNA Metabarcoding and Microscopy Techniques to Analyze Algal Diversity in Lake Titicaca, Peru
by Maribel Baylón and Jorge L. Ramirez
Diversity 2025, 17(8), 560; https://doi.org/10.3390/d17080560 - 7 Aug 2025
Abstract
The monitoring of algal communities has traditionally relied on optical microscopy. However, this technique is time-consuming and requires significant expertise to accurately identify species. In recent years, molecular techniques such as environmental DNA (eDNA) metabarcoding have facilitated the identification of algal communities. This [...] Read more.
The monitoring of algal communities has traditionally relied on optical microscopy. However, this technique is time-consuming and requires significant expertise to accurately identify species. In recent years, molecular techniques such as environmental DNA (eDNA) metabarcoding have facilitated the identification of algal communities. This study aims to compare both approaches for assessing planktonic microalgal communities in three areas of Lake Titicaca, using inverted light microscopy and eDNA metabarcoding. We found that the taxonomic composition obtained using the two methods differs significantly for Bacillariophyta, Chlorophyta, Charophyta, and Cyanobacteria, although genus- and order-level richness was similar across both approaches. A pronounced shift in species composition between techniques was revealed, with few shared genera and a high proportion of unassigned sequences (>50%) for Bacillariophyta. While microscopy provided more accurate estimates of microalgal density, metabarcoding revealed greater diversity, particularly among nanoplanktonic microalgae from the phyla Cryptophyta, Ochrophyta, Haptophyta, and Rhodophyta. To improve the accuracy and complementarity of these methodologies, it is essential to expand regional reference databases and work toward standardizing both approaches, allowing them to be used synergistically rather than independently. Full article
(This article belongs to the Special Issue Diversity and Ecology of Freshwater Plankton)
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14 pages, 6774 KiB  
Article
Antimicrobial Activities of Propolis Nanoparticles in Combination with Ampicillin Sodium Against Methicillin-Resistant Staphylococcus aureus
by Kaiyue Feng, He Sang, Han Jin, Peng Song, Wei Xu, Hongzhuan Xuan and Fei Wang
Microorganisms 2025, 13(8), 1844; https://doi.org/10.3390/microorganisms13081844 - 7 Aug 2025
Abstract
Combining antibiotics with propolis is an effective method to combat bacterial drug resistance. Nanoparticles are of interest in the antimicrobial field because of their higher drug stability, solubility, penetration power, and treatment efficacy. In this study, propolis nanoparticles (PNPs) were synthesized, and their [...] Read more.
Combining antibiotics with propolis is an effective method to combat bacterial drug resistance. Nanoparticles are of interest in the antimicrobial field because of their higher drug stability, solubility, penetration power, and treatment efficacy. In this study, propolis nanoparticles (PNPs) were synthesized, and their antibacterial and anti-biofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) in combination with ampicillin sodium (AS) were analyzed. The PNPs had an average particle diameter of 118.0 nm, a polydispersity index of 0.129, and a zeta potential of −28.2 mV. The fractional inhibitory concentration indices of PNPs and AS against tested MRSA strains highlighted this synergy, ranging between 0.375 and 0.5. Crystal violet staining showed that combined PNPs and AS significantly inhibited biofilm formation and reduced existing biofilm biomass. We then discovered that PNPs inhibited bacterial adhesion, extracellular polysaccharide synthesis, and mecR1, mecA, blaZ, and icaADBC gene expression. These results indicated that PNPs exerted a synergistic antibacterial effect with AS by inhibiting mecR1, mecA, and blaZ gene expressions to reduce the drug resistance of MRSA. Meanwhile, PNPs weakened bacterial adhesion and aggregation by suppressing icaADBC gene expression, allowing antibiotics to penetrate the biofilm, and exhibiting significant synergistic anti-biofilm activity. In summary, PNPs are promising candidates for combating MRSA-related diseases. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance, Second Edition)
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24 pages, 5480 KiB  
Article
Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas
by Jagoda Szkudlarek, Ludwika Piwowarczyk, Violetta Krajka-Kuźniak, Aleksandra Majchrzak-Celińska, Szymon Tomczak, Mikołaj Baranowski, Rafał Pietrzyk, Aneta Woźniak-Braszak and Anna Jelińska
Pharmaceutics 2025, 17(8), 1026; https://doi.org/10.3390/pharmaceutics17081026 - 7 Aug 2025
Abstract
Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their [...] Read more.
Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their low bioavailability requires nanotechnology solutions, such as liposomes. Methods: In this study, we propose the co-encapsulation of acteoside (ACT) with other natural compounds, cannabidiol (CBD) or naringenin (NG), in a cationic liposomal nanoformulation consisting of DOTAP and POPC lipids, which were prepared using the dry lipid film method. The liposomes were characterized by their physicochemical properties, including particle size, zeta potential, and polydispersity index (PDI), with additional analyses performed using 1H Nuclear Magnetic Resonance (NMR). Furthermore, biological experiments were performed with U-87 MG astrocytoma and U-138 MG GBM cell lines and non-cancerous MRC-5 lung fibroblasts using the MTT assay and evaluating the expression of Bax and Bcl-xL to evaluate their potential as anticancer agents. Conclusions: The IC50 values for the nanoformulations in U-138 MG cells at 48 h were 6 µM for ACT + CBD and 5 µM for ACT + NG. ACT and CBD or NG demonstrated a potential synergistic effect against GBM in a liposomal formulation. Notably, treatment with ACT + CBD (5 µM) and ACT + NG (5 µM) liposomal formulations significantly upregulated Bax protein level in U-138 cells at both 24 and 48 h. In parallel, ACT + CBD (5 µM) also modulated Bcl-xL protein level in both U-138 MG and U-87 MG cell lines at the same time points. The obtained nanoformulations were homogeneous and stable for 21 days, evidenced by a narrow particle size distribution, a low polydispersity index (PDI) < 0.3, and a positive zeta potential. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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21 pages, 885 KiB  
Article
Synergistic Effect of Community Environment on Cognitive Function in Elderly People
by Tao Shen, Ying Li and Man Zhang
Buildings 2025, 15(15), 2792; https://doi.org/10.3390/buildings15152792 - 7 Aug 2025
Abstract
With rapid global aging, the community environment has become a critical factor influencing cognitive health in older adults. However, most existing studies focus on single environmental attributes and rely on linear analytical methods, which fail to capture the complex and synergistic effects of [...] Read more.
With rapid global aging, the community environment has become a critical factor influencing cognitive health in older adults. However, most existing studies focus on single environmental attributes and rely on linear analytical methods, which fail to capture the complex and synergistic effects of community features. Guided by an integrated theoretical perspective on environmental psychology, aging, and cognitive health, this study examines how multiple community environmental factors jointly affect cognitive function in elderly people. A case study was conducted among 215 older residents in Shanghai, China. An exploratory factor analysis (EFA) identified the following five key dimensions of community environment: pedestrian friendliness, blue–green spaces, infrastructure, space attractiveness, and safety. We then applied both Partial Least Squares Structural Equation Modeling (PLS-SEM) and Fuzzy Set Qualitative Comparative Analysis (fsQCA) to reveal linear and configurational relationships. The findings showed that pedestrian friendliness, blue–green spaces, and space attractiveness significantly enhance cognitive health, while fsQCA highlighted multiple pathways that underscore the non-linear and synergistic interactions among environmental features. These results provide theoretical insights into the mechanisms linking community environments and cognitive function and offer practical guidance for designing age-friendly communities. Full article
(This article belongs to the Section Architectural Design, Urban Science, and Real Estate)
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16 pages, 1769 KiB  
Review
SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular–Kidney–Metabolic Syndrome
by Aryan Gajjar, Arvind Kumar Raju, Amani Gajjar, Mythili Menon, Syed Asfand Yar Shah, Sourbha Dani and Andrew Weinberg
Biomedicines 2025, 13(8), 1924; https://doi.org/10.3390/biomedicines13081924 - 7 Aug 2025
Abstract
Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose [...] Read more.
Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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27 pages, 15414 KiB  
Article
Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway
by Weijian Hu, Xin Xie and Jiabin Xu
Cells 2025, 14(15), 1214; https://doi.org/10.3390/cells14151214 - 7 Aug 2025
Abstract
Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed [...] Read more.
Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article
(This article belongs to the Section Cell Proliferation and Division)
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12 pages, 5474 KiB  
Article
Flexible Sensor with Material–Microstructure Synergistic Optimization for Wearable Physiological Monitoring
by Yaojia Mou, Cong Wang, Xiaohu Jiang, Jingxiang Wang, Changchao Zhang, Linpeng Liu and Ji’an Duan
Materials 2025, 18(15), 3707; https://doi.org/10.3390/ma18153707 - 7 Aug 2025
Abstract
Flexible sensors have emerged as essential components in next-generation technologies such as wearable electronics, smart healthcare, soft robotics, and human–machine interfaces, owing to their outstanding mechanical flexibility and multifunctional sensing capabilities. Despite significant advancements, challenges such as the trade-off between sensitivity and detection [...] Read more.
Flexible sensors have emerged as essential components in next-generation technologies such as wearable electronics, smart healthcare, soft robotics, and human–machine interfaces, owing to their outstanding mechanical flexibility and multifunctional sensing capabilities. Despite significant advancements, challenges such as the trade-off between sensitivity and detection range, and poor signal stability under cyclic deformation remain unresolved. To overcome the aforementioned limitations, this work introduces a high-performance soft sensor featuring a dual-layered electrode system, comprising silver nanoparticles (AgNPs) and a composite of multi-walled carbon nanotubes (MWCNTs) with carbon black (CB), coupled with a laser-engraved crack-gradient microstructure. This structural strategy facilitates progressive crack formation under applied strain, thereby achieving enhanced sensitivity (1.56 kPa−1), broad operational bandwidth (50–600 Hz), fine frequency resolution (0.5 Hz), and a rapid signal response. The synergistic structure also improves signal repeatability, durability, and noise immunity. The sensor demonstrates strong applicability in health monitoring, motion tracking, and intelligent interfaces, offering a promising pathway for reliable, multifunctional sensing in wearable health monitoring, motion tracking, and soft robotic systems. Full article
(This article belongs to the Special Issue Advanced Materials for Flexible Sensing Applications and Electronics)
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