Search Results (16,638)

Background/Objectives: Peri-implantitis is a chronic inflammatory condition affecting tissues surrounding dental implants and is characterized by progressive marginal bone loss that can ultimately lead to implant failure. Reduced vascularization and impaired immune clearance in peri-implant tissues contribute to persistent inflammation and limited therapeutic efficacy. MicroRNAs (miRNAs), particularly miR-21, have emerged as key regulators of inflammatory responses and bone remodeling. The objective of this study was to develop a bioactive dental implant coating capable of locally delivering miR-21 to modulate inflammation and promote peri-implant tissue regeneration, thereby preventing peri-implantitis. Methods: Cationic nanoparticles were synthesized using lecithin and low-molecular-weight polyethylenimine (PEI) as a non-viral delivery system for miR-21. Lecithin was employed to enhance biocompatibility, while PEI functionalization provided a positive surface charge to improve miRNA complexation and cellular uptake. The resulting lecithin–PEI nanoparticles (LEC–PEI NPs) were incorporated into a chitosan-based coating and applied to titanium implant surfaces to obtain a sustained miR-21–releasing system (miR21-implant). Transfection efficiency and biological activity were evaluated in human periodontal ligament fibroblasts (hPDLFs) and compared with a commercial transfection reagent (Lipofectamine). Release kinetics and long-term activity of miR-21 from the coating were also assessed. Results: MiR-21-loaded LEC–PEI nanoparticles demonstrated significantly higher transfection efficiency than Lipofectamine and retained marked biological activity in hPDLFs relevant to peri-implantitis prevention. The chitosan-based nanoparticle coating enabled controlled and sustained miR-21 release over time, supporting prolonged modulation of inflammatory and osteogenic signaling pathways involved in peri-implant tissue homeostasis. Conclusions: The miR21-implant system, based on lecithin–PEI nanoparticles incorporated into a chitosan coating, represents a promising therapeutic strategy for peri-implantitis prevention. By enabling sustained local delivery of miR-21, this approach has the potential to preserve peri-implant bone architecture, modulate chronic inflammation, and enhance the osseointegration of titanium dental implants. Full article

The phaeozem in Northeast China is rich in soil organic carbon (SOC). However, the excessive and inefficient application of chemical fertilizers, particularly nitrogen fertilizers, has primarily led to a decrease in soil pH in this region. Currently, the relationship between soil pH and the stability of soil organic carbon (SOC) remains ambiguous. This study, conducted over 13 years of field experiments, focused on soils exhibiting varying degrees of pH resulting from different nitrogen application rates. The research employed aggregate classification, ¹³C nuclear magnetic resonance spectroscopy, and analysis of microbial community composition to investigate the alterations in the SOC stabilization mechanisms under varying nitrogen application levels. Our results demonstrated that the decline in soil pH led to reductions in macroaggregates (>2 mm) and the soil aggregate destruction rate (PAD) by 4.8–14.6%, and in soil aggregate unstable agglomerate index (E_LT) by 9.7–13.4%. The mean weight diameter (MWD) and geometric mean diameter (GMD) exhibited significant declines (p < 0.05) with decreasing pH levels. According to the ¹³C NMR analysis, the SOC was predominantly composed of O-alkyl carbon and aromatic carbon. At a pH of 5.32, the Alip/Arom values decreased, while the molecular structure of SOC became more complex under different levels of pH. In addition, the increase in [Fe(Al)-OC] (31.4–71.9%) complex indicates a shift in the stability of organic carbon from physical protection to organic mineral binding. Declining soil pH significantly reduced the diversity of soil microbial communities and promoted a shift toward copiotrophic microbial groups. Overall, declining soil pH resulted in a decline in soil aggregate stability and an increase in SOC aromaticity. This drove the shift in the stabilization mechanism of SOC in the black soil ecosystem of meadows in Northeast China from physical protection to chemical stability. Full article

Nicotinic acetylcholine receptors (nAChRs) are membrane-bound proteins that mediate fast synaptic transmission throughout the nervous system. A functional nAChR subtype is formed by the combination of multiple subunits arranged as homomeric or heteromeric pentamers, each with a distinct pharmacological profile. Disruption of their neurotransmission contributes to various neuropathologies, emphasizing the need for detailed knowledge of receptor structure, function, subunit composition, dynamics, and potential ligand-binding sites. However, their structural complexity as integral membrane proteins has hindered expression in mammalian cell lines and proven even more challenging to crystallize, limiting insights into ligand interactions. Understanding the molecular determinants governing nAChRs function is essential for the rational design of selective therapeutics targeting neurological disorders. The emergence of a chimeric receptor approach has dramatically improved the ability to study these important proteins and opened new avenues for high-throughput screening in drug discovery efforts. This review explains how the design of chimera constructs using soluble homologs, such as AChBP, provides researchers with an immense opportunity to investigate receptor structure–function relationships and subtype-specific properties, thereby facilitating the development of more effective treatments. Full article

Klebsiella pneumoniae is commonly known to cause a vast range of community-acquired or nosocomial infections. The isolation of K. pneumoniae has also been noted in diseased food-producing animals, including swine. The main goals of this study were to document clinical manifestation of a septicaemia outbreak in suckling piglets due to K. pneumoniae ST25 and provide molecular characterisation of the isolates. For the purpose of this investigation, 13 dead suckling piglets with cyanosis were selected. All the isolates obtained from affected lungs were susceptible to apramycin, ceftiofur, gentamycin, neomycin, and spectinomycin, presented intermediate susceptibility to florfenicol, and were resistant to other tested antibiotics. Histopathological examination of lungs, kidneys, and livers revealed lesions typical of septicaemia. MLST analysis of the isolates demonstrated a complex metabolic profile of the bacteria with genes attributable to the hypervirulent phenotype. To the best of our knowledge, we documented the first outbreak of K. pneumoniae septicaemia in suckling piglets reared in Poland. Full article

The widespread occurrence of pharmaceutical residues in aquatic environments necessitates the development of advanced porous materials for efficient remediation. This study investigates the adsorption mechanisms of ibuprofen and atenolol within the high-silica zeolite Y. Batch adsorption experiments demonstrated significant uptake, with loading capacities of 191.6 mg/g for ibuprofen and 273.0 mg/g for atenolol, confirming the material’s effectiveness. Using a combination of neutron and X-ray powder diffraction, complemented by Rietveld refinement and simulated annealing algorithms, we achieved the exact localization of the guest molecules. While the pristine zeolite maintains cubic symmetry $Fd\overline{3}$, the incorporation of pharmaceutical molecules induces significant residual nuclear density and anisotropic lattice distortions. To accurately model these perturbations, a systematic symmetry reduction to the acentric triclinic space group F1 was implemented. This approach enabled an ab initio refinement of the structure, revealing that drug uptake of each guest is governed by distinct chemical drivers. Ibuprofen is stabilized via steric confinement and long-range dispersive interactions. In contrast, atenolol stability is governed by electrostatic charge compensation within the zeolitic voids. Our results suggest that the final adsorption geometry is dictated by the spatial orientation of functional groups and host–guest proximity rather than molecular chirality. These results provide a microscopic model describing the fundamental host–guest interactions in FAU zeolites. This structural understanding is an essential step towards the potential use of zeolitic materials in environmental remediation and complex guest sequestration. Full article

Waterlogging stress severely limits crop photosynthesis and energy supplies, resulting in significant yield reductions. However, the critical duration of waterlogging stress during the maize jointing stage remains unclear, and the physiological and molecular mechanisms underlying its effects on photosynthetic efficiency and energy synthesis in maize require further investigation. In this study, we systematically analyzed the responses of physiological traits, transcriptomic profiles, and the yield formation in maize (Zea mays L.) to varying waterlogging durations imposed during the jointing stage, including 0 days (CK), 2 days (F2), 4 days (F4), 6 days (F6), 8 days (F8), and 10 days (F10). Our results indicate that the (1) grain weight (GW) showed no significant difference between F2 and CK. However, the GW in F4, F6, F8, and F10 decreased significantly by 17.49%, 26.45%, 60.24%, and 100.00%, respectively, compared to the CK. (2) Compared with the CK, the malondialdehyde content progressively increased from F4 to F10, while antioxidant enzyme activity gradually decreased. The chlorophyll content declined by 29.93% to 57.38%, and net photosynthetic efficiency decreased by 13.82% to 38.93%. Although the leaf sucrose content in from F4 to F10 gradually decreased, the leaf starch content remained stable in F4 and F6. In contrast, the starch content in F8 and F10 leaves was significantly reduced by 37.55% and 47.60%, respectively, compared with CK. (3) A transcriptomic analysis revealed that during from F2 to F4, genes encoding photosystem I subunit protein, such as PSAD, and the cytochrome b6f complex proteingene PETC were downregulated. At F6, these key genes encoding photosynthetic proteins were upregulated. However, at F8 and F10, their expression was significantly downregulated. Concurrently, genes related to ATP synthesis (e.g., ATPD) as well as starch and sucrose metabolism (e.g., SPP2, SS1) were also downregulated. In summary, when waterlogging stress persists for no longer than 6 days, plants can maintain their starch content to supply energy for growth, thereby ensuring basic developmental needs. When waterlogging persists for more than 6 days, energy synthesis is impaired, and the nutrient transport to the grains is significantly inhibited, ultimately resulting in a substantial reduction in yield. Therefore, 6 days of waterlogging can be considered the critical threshold for significant yield loss in maize during the jointing stage. Full article

Lignin, the most abundant renewable source of aromatic compounds, plays a pivotal role in advancing sustainable biorefineries and reducing dependence on fossil resources. Recent progress in integrated lignin valorization pathways has unlocked opportunities to convert this complex biopolymer into high-value chemicals, materials, and energy carriers, despite its structural heterogeneity and recalcitrance posing major challenges. This review highlights the significant advancements in depolymerization strategies, including catalytic, oxidative, and biological approaches, which are reinforced by innovations in catalyst design and reaction engineering that enhance selectivity and efficiency. It also discusses emerging technologies, such as hybrid chemo-enzymatic systems, solvent fractionation, and continuous-flow reactors, for their potential to improve scalability and sustainability. Furthermore, this review examines the integration of lignin valorization with upstream pretreatment and downstream recovery, emphasizing process intensification, co-product synergy, and techno-economic optimization to achieve commercial viability. Despite these developments, critical gaps remain in understanding the molecular complexity of lignin, developing universally applicable catalytic systems, and optimizing economic and environmental performance. To guide future research, it poses two key questions: how to design catalysts for selective depolymerization across diverse lignin sources, and how to configure biorefineries for maximum lignin utilization while ensuring sustainability? Addressing these challenges will be essential for lignin’s role in next-generation biorefineries and a circular bioeconomy. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by persistent memory impairment and complex molecular and cellular pathological changes in the brain. Current treatments, including acetylcholinesterase inhibitors and memantine, only help with symptoms for a short time and do not stop the disease from getting worse. This is mainly because these drugs do not reach the brain well and are quickly removed from the body. The blood–brain barrier (BBB) restricts the entry of most drugs into the central nervous system; therefore, new methods of drug delivery are needed. Nanotechnology-based drug delivery systems (NTDDS) are widely studied as a potential approach to address existing therapeutic limitations. Smart biosensing nanoparticles composed of polymers, lipids, and metals can be engineered to enhance drug stability, improve drug availability, and target specific brain regions. These smart nanoparticles can cross the BBB via receptor-mediated transcytosis and other transport routes, making them a promising option for treating AD. Additionally, multifunctional nanocarriers enable controlled drug release and offer theranostic capabilities, supporting real-time tracking of AD treatment responses to facilitate more precise and personalized interventions. Despite these advantages, challenges related to long-term safety, manufacturing scalability, and regulatory approval remain. This review discusses current AD therapies, drug-delivery strategies, recent advances in nanoparticle platforms, and prospects for translating nanomedicine into effective, disease-modifying treatments for AD. Full article

Natural rubber biosynthesis is catalyzed by a unilamella membrane-bound heterologous complex with multiple different subunits (rubber transferase, RTase). Two substrates and divalent metal cation activators are required, and their concentrations affect biosynthetic rate and polymer molecular weight. Rate, molecular weight, and complex stability are highly sensitive to Mg²⁺ and Mn²⁺ concentration, but studies are challenging because methods to control ion concentration may dislodge the elongating rubber polymers from the RTase complexes, halting synthesis and producing low-molecular-weight polymer. Here, programmable chemical actuators (PCAs) are used to electrochemically control rubber biosynthetic rate and subsequent molecular weight in enzymatically active rubber particles purified from Ficus elastica (Indian rubber tree). RTase activity was assayed using ³H-FPP (initiator) and ¹⁴C-IPP (monomer). Since only one FPP molecular is needed to initiate a new rubber polymer, the ratio of incorporated ³H-FPP to ¹⁴C-IPP was used to calculate the mean molecular weight of newly synthesized polymers. PCAs exchange ions in solution through REDOX reactions which we show control cation concentration without dislodging the elongating rubber polymers from the RTase. PCAs demonstrated highly tunable control over monomer incorporation and molecular weight in both Mg²⁺ and Mn²⁺ cations. REDOX cycling PCAs did not irreversibly inhibit the rubber transferase complex, and no indication of enzymatic damage was observed. Precise PCA control of RTase activity may pave the way for rubber eventually to be produced in bioreactors. Full article

Understanding mechanisms of asphalt in the process of natural aging is crucial for predicting its long-term durability and optimizing performance under diverse environmental conditions. Despite its importance, the microstructural and micromechanical changes induced by natural aging remain poorly understood, particularly under varying climatic influences. This study addresses this gap by analyzing the effects of natural aging on asphalt’s microscopic properties and identifying key indicators that govern its degradation. Asphalt samples were subjected to natural aging across five climatically distinct regions over 6, 12, and 18 months. Atomic force microscopy (AFM) was employed to characterize surface roughness, adhesion forces, and DMT modulus, while correlation analysis and principal component analysis (PCA) were used to identify relationships among micromechanical indicators and streamline the dataset. The results reveal that natural aging induces irreversible transformations in asphalt’s microstructure, driven by the combined effects of temperature, UV radiation, humidity, and oxygen. These processes promote the evolution of “Bee structures,” increase surface roughness, and accelerate phase separation, alongside chemical modifications such as oxidation and polymerization, leading to progressive material hardening and stiffness. Significant regional and temporal variations in adhesion forces and DMT modulus were observed, reflecting the cumulative impact of environmental factors on asphalt’s aging dynamics. Correlation analysis demonstrated strong associations between surface roughness and “Bee structure” area, while mechanical properties such as stiffness and adhesion were largely decoupled from morphological features. Environmental factors interact in complex ways to drive asphalt aging. Humidity enhances adhesion and stiffness via water-induced capillary forces, while temperature reduces surface roughness and adhesion through molecular reorganization. UV radiation accelerates oxidative degradation, promoting surface erosion and stiffness loss, while altitude modulates these dynamics by influencing temperature and UV exposure. Full article

The use of lecithin as an emulsifier in food supplements has increased in recent years. However, successful formation of liposomes or micelles requires an appropriate mixture of phospholipids in lecithin. To evaluate the emulsification properties of lecithin for food supplements, a reliable analytical procedure for characterizing phospholipids is necessary. A liquid chromatography–mass spectrometry method was developed to identify phospholipids in lecithin without standard reference materials. For efficient separation of phospholipids before mass spectrometric analysis, a reverse-phase high-performance liquid chromatography method was optimized using a Waters XBridge Protein BEH C4 column. The optimized chromatographic method demonstrated good linearity and precision. Molecular ions were detected in full scan mode to determine accurate mass-to-charge ratios for individual peaks in the chromatogram. A custom Python program was then used to generate a list of possible phospholipid species for each peak based on the measured mass-to-charge ratios. Tandem mass spectrometry was performed to confirm the identity of specific phospholipids by comparing experimental fragmentation patterns with theoretical predictions. Identification of the phospholipids was also confirmed with four commercially available standard reference compounds, demonstrating the reliability of the proposed approach. The developed method offers a practical and cost-effective strategy for identifying phospholipids in complex matrices, especially when standard reference compounds are unavailable. Additionally, it enables targeted selection of standard compounds for future quantitative analyses, making it a valuable tool for comprehensive lipid profiling. Full article

This review aims to provide a broad, multidisciplinary perspective on how dynamic genomics and systems biology are transforming modern healthcare, with a focus on cancer especially liver cancer (HCC). It explains how integrating multi-omics technologies such as genomics, transcriptomics, proteomics, interactomics, metabolomics, and spatial transcriptomics deepens our understanding of the complex tumor environment. These innovations enable precise patient stratification based on molecular, spatial, and functional tumor characteristics, allowing for personalized treatment plans. Emphasizing the role of regulatory networks and cell-specific pathways, the review shows how mapping these networks using multi-omics data can predict resistance, identify therapeutic targets, and aid in the development of targeted therapies. The approach shifts from standard, uniform treatments to flexible, real-time strategies guided by technologies such as liquid biopsies and wearable biosensors. A case study showcases the benefits of personalized therapy, which integrates epigenetic modifications, checkpoint inhibitors, and ongoing multi-omics monitoring in a patient with HCC. Future innovations, such as cloud-based genomic ecosystems, federated learning for privacy, and AI-driven data analysis, are also discussed to enhance decision-making and outcomes. The review underscores a move toward predictive and preventive healthcare by integrating layered data into clinical workflows. It reviews ongoing clinical trials using advanced molecular and immunological techniques for HCC. Overall, it promotes a systemic, technological, and spatial approach to cancer treatment, emphasizing the importance of experimental, biochemical–functional, and biophysical data-driven insights in personalizing medicine. Full article

Mitochondrial dysfunction contributes to impaired myocardial energetics and performance in heart failure with preserved ejection fraction (HFpEF). Elamipretide (Ela) enhances mitochondrial bioenergetics in preclinical models, yet its relevance in HFpEF remains unclear. This study examined the effects of Ela on cardiac mitochondrial function, structure, and cardiovascular performance in a rodent HFpEF model. Female obese ZSF1 rats received vehicle or Ela for 12 weeks, with age-matched lean rats as controls. Cardiac function and hemodynamics were assessed by echocardiography and pressure–volume analysis. Mitochondrial respiration was measured in permeabilized fibers and ultrastructure evaluated by transmission electron microscopy. Molecular and histological analyses included cardiolipin lipidomics and mRNA/protein profiling of hypertrophic, fibrotic, and inflammatory markers. Ela modestly improved complex I and II respiration, whereas mitochondrial ultrastructure, cardiolipin composition, and tafazzin expression were unchanged. Diastolic dysfunction persisted, reflected by unchanged E/é, ventricular stiffness factor β, and titin phosphorylation. Compared to untreated HFpEF, systolic performance showed a mild decline, with small reductions in LV ejection fraction and end-systolic elastance. Accordingly, cardiac remodeling, including hypertrophy, fibrosis, and inflammatory activation, remained unaltered. Vascular stiffness slightly increased, while carotid reactivity and morphology were preserved. In conclusion, despite enhanced mitochondrial respiration following Ela treatment, no functional or structural benefits were observed in experimental HFpEF, suggesting limited therapeutic efficacy once HFpEF is established. Full article

Platelet-rich plasma (PRP) is a cornerstone of regenerative medicine, offering therapeutic potential across numerous clinical disciplines. Its efficacy relies on concentrated platelets and plasma components that release growth factors, cytokines, and extracellular vesicles to orchestrate tissue repair, immunomodulation, and angiogenesis. Recent findings have uncovered novel mechanisms, such as mitochondrial transfer from platelets to target cells and the delivery of bioactive microRNAs that regulate inflammation and metabolic reprogramming. However, despite its potential, PRP therapy is often limited by inconsistent results. In this review, we examine how patient-specific factors—including age, comorbidities, and lifestyle—and technical variables in preparation and storage, influence the biological quality of the final product. Therefore, standardizing protocols and accounting for individual biological variability are essential for achieving reproducible outcomes. In conclusion, PRP is a complex therapeutic agent whose success depends on both intrinsic bioactive content and extrinsic processing factors. Integrating these molecular insights with personalized patient assessment is crucial to optimizing PRP treatment procedures. Future research should focus on refining standardization to fully establish PRP as a precision medicine tool in regenerative therapy. Full article

Helicobacter pylori (H. pylori) is recognized as one of the most widespread and persistent bacterial infections globally, with a remarkable ability to colonize the human stomach. This pathogen is a major contributor to the development of gastric diseases, including gastric lymphoma and adenocarcinoma. The H. pylori infection triggers a complex pathogenic cascade within the gastric environment, characterized by prolonged inflammation and heightened oxidative stress, which fosters a milieu of immune dysregulation, where both innate and adaptive immune cells become activated inappropriately, thereby leading to epithelial injury and subsequent remodeling of the gastric tissue. As the infection persists, repeated cycles of inflammation and epithelial damage contribute to the development of epigenetic alterations, including changes in DNA methylation, histone modifications, and non-coding RNA expression, all of which render the gastric epithelium more susceptible to further aberrations, including dysplasia and cancer. In this article, we review the latest advances in understanding the molecular mechanisms of H. pylori-induced gastritis and its role in the progression of gastric cancer, offering new perspectives on the complex biology of this infection and its potential therapeutic implications for preventing the development of gastric malignancies. Full article