Search Results (102)

Lipid-polymer hybrid nanoparticles (LPHNPs) are the next-generation nanocarriers that integrate the mechanical strength and sustained-release capacity of polymeric cores with the biocompatibility and high drug-loading efficiency of lipid shells. Various design strategies and architectures that enhance encapsulation efficiency, stability, and targeted delivery of diverse therapeutic agents are reviewed. Commonly employed polymers, lipids, and surfactants that enable controlled drug release and enhanced pharmacokinetic performance are summarized in tabular form, while fabrication methods such as single-step, emulsification-solvent evaporation, and microfluidic techniques are discussed for their scalability and reproducibility. The therapeutic potential of LPHNPs in delivering poorly soluble drugs, phytochemicals, and genetic materials achieving synergistic therapeutic outcomes in oncological applications is comprehensively highlighted. The manuscript also includes details on ligand-based functionalization and the integration of imaging and stimuli-responsive elements to enhance targeted delivery and develop multifunctional theranostic LPHNPs systems. Furthermore, non-oncologic applications of LPHNPs in ocular, topical, and oral delivery are discussed, emphasizing their potential in treating inflammatory, infectious, and autoimmune disorders with sustained release and enhanced therapeutic efficacy. Recent patents focusing on improved biocompatibility, dual-drug encapsulation, and mRNA delivery are summarized. However, challenges such as large-scale production, reproducibility, safety, and regulatory standardization must be addressed through quality by design approaches and advanced manufacturing technologies to fully realize the clinical and commercial potential of next-generation LPHNPs. Full article

Oxidative stress (OS), defined as a disturbance in the balance between the production and elimination of reactive oxygen species (ROS), has been widely recognized as a key factor in the pathogenesis of various aquatic animal diseases. With the intensification of aquaculture and increasing environmental pressure, aquatic animals are frequently subjected to stressors that trigger oxidative stress, thereby compromising their health and productivity. This review comprehensively summarizes recent advances in understanding the involvement of oxidative stress in multiple organ-related diseases in farmed aquatic animals, including hepatic/pancreatic injuries, gill lesions, muscle degeneration, skin and shell disorders, metabolic disruptions, immunosuppression, and reproductive impairments. The underlying mechanisms involve excessive ROS-induced lipid peroxidation, inflammation, mitochondrial dysfunction, and the disruption of critical signaling pathways. Additionally, recent advances in nutritional antioxidants (e.g., vitamins, plant extracts), environmental regulation, and feed additives for mitigating oxidative damage are also discussed. A comprehensive understanding of the pathogenesis and regulation of oxidative stress is essential for improving aquatic animal health and enhancing the sustainability of aquaculture systems. Full article

Using molecular dynamics (MDs) simulations with Materials Studio 8.0 software, we systematically investigated the adsorption and aggregation behaviors of silicon, tin, and copper atoms on the surface of (7,7) single-walled carbon nanotubes (SWCNTs). Silicon, tin, and copper were selected due to their distinct bonding characteristics—covalent (Si), semi-metallic (Sn), and metallic (Cu)—and their relevance in potential composite interface applications such as energy storage, thermal management, and electronics. The results indicate that silicon atoms form multi-layered concentric shells; however, the rigidity of their covalent bonds makes the resulting structures susceptible to disruption by local density fluctuations. Tin atoms form a limited number of stable concentric shells benefiting from the flexibility of their semi-metallic bonds. In contrast, copper atoms rapidly aggregate into disordered clusters due to their high diffusivity and metallic bonding. Within the confined geometry of the carbon nanotubes, all three types of atoms exhibit a tendency toward spiral growth, but their regularity depends on the properties of their chemical bonds, leading to distinct spiral features. These findings are further supported by linear density and radial distribution function (RDF) analyses. Full article

Background/Objectives: Chronic retinal diseases usually require repetitive local dosing. Depending on factors such as dosing frequency, mode of administration, and associated costs, this can result in poor patient compliance. A better alternative involves using controlled-release drug delivery systems to reduce the frequency of intravitreal dosing and extend drug release. However, reaching the market stage is a time-consuming process. Methods: In this study, we employed two computational approaches to model and estimate the parameters governing the diffusion-controlled drug release from bi-layered microspheres. The case study involved microspheres composed of a chitosan core and a polycaprolactone (PCL) shell. The model drugs were bovine serum albumin and bevacizumab (an agent that slows neovascularization due to retinal disorders). Drug release from the microspheres is described by a mathematical model that was solved numerically using the finite difference and the finite element approaches. The parameter estimation was performed by nonlinear least-squares regression. Results: We used the estimated parameters to simulate the cumulative release under various conditions and optimize the device design to guide future experimental efforts and improve the duration of release beyond a target daily therapeutic release rate from the microspheres. Conclusions: We investigated the effects of polymeric layer sizes on drug release and provided recommendations for optimal sizes. We provide straightforward computational tools for others to reuse in designing bi-layered microspheres for intravitreal drug delivery needs in the treatment of chronic ocular neovascularization. Full article

Nacre, the iridescent inner layer of mollusk shells, has long been traditionally used in medicine. While we have previously demonstrated its anti-aging effects on muscle and skin, its impact on pancreatic dysfunction and glucose metabolism remains unclear. In this study, we aimed to isolate and identify an active component from nacre extract that improves glucose metabolism and to evaluate its potential to prevent or ameliorate pancreatic dysfunction and glucose metabolic abnormalities in a D-galactose-induced aging mouse model. A polysaccharide component was successfully isolated using a combination of reverse-phase and ion-exchange chromatography. Structural analyses revealed that it was primarily composed of glucose, mannose, and rhamnose, which together accounted for approximately 87% of the total monosaccharide content. Further characterization by FT-IR spectroscopy and MALDI-TOF-MS confirmed its identity as a neutral polysaccharide with glycosidic linkages and an estimated molecular weight of approximately 5000 Da. Intraperitoneal administration of this polysaccharide significantly improved glucose tolerance and prevented a decline in serum insulin levels in D-galactose-induced aging mice. Immunohistochemical analysis of pancreatic tissues revealed that the polysaccharide preserved insulin expression and suppressed the D-galactose-induced upregulation of cellular senescence and apoptosis markers. These findings suggest that this nacre-derived polysaccharide effectively mitigates pancreatic dysfunction and glucose metabolic dysfunction, indicating its potential as a natural therapeutic agent for age-related metabolic disorders. Full article

This study presents the development and the mechanical and clinical characterization of a flexible biodegradable chitosan–glycerol–graphite composite strain sensor for real-time respiratory monitoring, where the main material, chitosan, is derived and extracted from Tenebrio Molitor larvae shells. Chitosan was extracted using a sustainable, low-impact protocol and processed into a stretchable and flexible film through glycerol plasticization and graphite integration, forming a conductive biocomposite. The sensor, fabricated in a straight-line geometry to ensure uniform strain distribution and signal stability, was evaluated for its mechanical and electrical performance under cyclic loading. Results demonstrate linearity, repeatability, and responsiveness to strain variations in the stain sensor during mechanical characterization and performance, ranging from 1 to 15%, with minimal hysteresis and fast recovery times. The device reliably captured respiratory cycles during normal breathing across three different areas of measurement: the sternum, lower ribs, and diaphragm. The strain sensor also identified distinct breathing patterns, including eupnea, tachypnea, bradypnea, apnea, and Kussmaul respiration, showing the capability to sense respiratory cycles during pathological situations. Compared to conventional monitoring systems, the sensor offers superior skin conformity, better adhesion, comfort, and improved signal quality without the need for invasive procedures or complex instrumentation. Its low-cost, biocompatible design holds strong potential for wearable healthcare applications, particularly in continuous respiratory tracking, sleep disorder diagnostics, and home-based patient monitoring. Future work will focus on wireless integration, environmental durability, and clinical validation. Full article

Background/Objectives: Chestnut inner shells, traditionally used in Korean and Chinese herbal medicine, contain antioxidant and anti-inflammatory compounds that contribute to complementary medicine. This study aimed to explore the therapeutic effects of chestnut inner-shell extract (CIE) on skeletal muscle injury and atrophy using both in vivo and in vitro models. Methods: We used three experimental models representing distinct pathological mechanisms: (1) barium chloride (BaCl₂)-induced muscle injury to model acute myofiber damage, (2) sciatic nerve transection to model chronic neurogenic muscle atrophy, and (3) H₂O₂-treated C2C12 myoblasts to model oxidative-stress-related myogenic impairment. Histological analyses (e.g., hematoxylin and eosin staining and cross-sectional area measurement) and molecular analyses were performed to evaluate the effects of CIE on muscle structure, apoptosis, and oxidative stress. Results: In the BaCl₂ injury model, CIE treatment significantly restored the muscle fiber structure, with muscle protein levels returning to near-normal levels. In the denervation-induced muscle atrophy model, CIE treatment led to a dose-dependent decrease in apoptosis-related factors (especially cleaved caspase-3) and mitigated the Akt/mTOR signaling pathway. In the in vitro oxidative stress model, CIE suppressed the expression of NRF2 and HO-1, which are key oxidative stress response regulators. Conclusions: These findings suggest that CIE may offer therapeutic potential for mitigating skeletal muscle damage, atrophy, and oxidative stress. Full article

This study evaluates the effects of solid-state fermentation inoculated with Aspergillus spp. on the nutritional profile of selected agro-industrial by-products (AIBPs: cowpea shell, groundnut shell, soybean hull, and maize shaft). These AIBPs were assessed as potential feedstuffs in weaner rabbit diets, which often exhibit digestive disorders when introduced to highly lignified feed ingredients. The AIBPs were milled to a particle size of 2 mm, sterilized, and subjected to fermentation with Aspergillus spp. under microaerophilic conditions at 28 ± 2 °C for 10 days. Samples (four replicates per treatment) were analyzed for chemical constituents (mineral and proximate composition, anti-nutritional factors, and fibre fractions) before and after fermentation. Digestible energy and digestibility coefficient of gross energy were calculated. Data were subjected to two-way analysis of variance (ANOVA). There was an increase (p < 0.05) in mineral profile, proximate composition, digestible energy, digestibility coefficient of gross energy, and dry matter, with a reduction (p < 0.05) in crude fibre, fibre fractions, and anti-nutritional factors. It was concluded that fermentation with Aspergillus spp. improved the nutritional value of the selected agro-industrial by-products. Therefore, fermented materials possess a better nutritional profile to be used in feeding programs for weaner rabbits. This will ensure sustainable animal production and add value to agricultural waste, which would otherwise constitute an environmental nuisance. Full article

Proteins and their surrounding hydration water engage in a dynamic interplay that is critical for maintaining structural stability and functional integrity. However, the intricate coupling between protein dynamics and the structural order of hydration water remains poorly understood. Here, we employ all-atom molecular dynamics simulations to investigate this relationship across four representative proteins. Our results reveal that protein residues with greater flexibility or solvent exposure are surrounded by more disordered hydration water, akin to bulk water, whereas rigid and buried non-polar residues are associated with structurally ordered hydration shells. Due to their strong hydrogen bonding and electrostatic interactions, charged residues exhibit the most disordered hydration water, while non-polar residues are associated with the structurally most ordered hydration water. We further uncovered a positive correlation between the relaxation dynamics of protein residues and their hydration water: slower (faster) protein relaxation is coupled with slower (faster) relaxation of the structural order of hydration water. Notably, this coupling weakens with increasing residue flexibility or solvent exposure, with non-polar residues displaying the strongest coupling, and charged residues the weakest. To further uncover their coupling mechanism, we elucidate residue-specific coupled fluctuations between protein residues and hydration water by generating scatter plots. These findings provide a comprehensive understanding of the mechanisms underlying protein–water interactions, offering valuable insights into the role of hydration water in protein stability, dynamics, and function. Full article

Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived F_oF₁-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded F_oF₁-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30–40 μm vs. 15–25 μm in untreated). These results highlight the ATM’s potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity. Full article

This study explores the structural and chemical interactions between glacial water, ice I_h, and hydration clusters of divalent cations (Ca²⁺ and Mg²⁺). Ice I_h, with its hexagonal lattice and tetrahedral bonding network, is incompatible with the hydration shells of Ca²⁺ and Mg²⁺, which adopt octahedral geometries in aqueous solutions. During freezing, these hydration clusters become disordered, causing distortions in the ice structure. Slow freezing reduces these distortions, while rapid freezing traps ions in amorphous regions, preventing proper alignment of hydration clusters. Through advanced techniques such as chemical and isotopic analysis, computational modeling, and electrical impedance spectroscopy, this study examines ion exclusion mechanisms and water-clustering behaviors. The results show that both ions are largely excluded from the solid phase during freezing, with Mg²⁺ exhibiting stronger exclusion due to its smaller ionic radius and greater hydration energy. This study also highlights the role of sediments in modulating ion patterns in glacial ice. This work deepens our understanding of ion–ice interactions, offering insights for cryochemistry, hydrology, and environmental science. The integration of experimental and computational methods provides new perspectives on divalent cations’ role in modifying ice’s crystalline structure and explains isotopic variability in glacial waters. Full article

This study employed a hydrothermal method to coat CuS onto PbS quantum dots loaded with ZnO, resulting in a core–shell-structured (PbS/ZnO)@CuS hetero-structured photocatalyst. The sulfide coating enhanced the photocatalyst’s absorption in the near-infrared to visible light range and effectively reduced electron–hole (h⁺) pair recombination during photocatalytic processes. Electron microscopy analysis confirmed the successful synthesis of this core–shell structure using polyvinylpyrrolidone (PVP); however, the spatial hindrance effect of PVP led to a disordered arrangement of the CuS lattice, facilitating electron–hole recombination. Comprehensive analyses using transmission electron microscopy (TEM), photoluminescence (PL), and Brunauer–Emmett–Teller (BET) methods revealed that the (PbS/ZnO)@CuS photocatalyst synthesized at a hydrothermal temperature of 170 °C exhibited optimal hydrogen production efficiency. After conducting a photocatalytic reaction for 5 h in a mixed aqueous solution containing 0.25 M Na₂S + Na₂SO₃ as a sacrificial agent, a hydrogen production rate of 3473 μmol·g⁻¹·h⁻¹ was achieved. Full article

Background/Objective: There is strong evidence that the tripartite interaction between glucose homeostasis, gut microbiota, and the host immune system plays a critical role in the pathophysiology of type 2 diabetes mellitus (T2DM). We reported previously that peanut shell extract (PSE) improves mitochondrial function in db/db mice by suppressing oxidative stress and inflammation in the liver, brain, and white adipose tissue. This study evaluated the impacts of PSE supplementation on glucose homeostasis, liver histology, intestinal microbiome composition, and the innate immune response in diabetic mice. Methods: Fourteen db/db mice were randomly assigned to a diabetic group (DM, AIN-93G diet) and a PSE group (1% wt/wt PSE in the AIN-93G diet) for 5 weeks. Six C57BL/6J mice received the AIN-93G diet for 5 weeks (control group). Parameters of glucose homeostasis included serum insulin, HOMA-IR, HOMA-B, and the analysis of pancreatic tissues for insulin and glucagon. We assessed the innate immune response in the colon and liver using a microarray. Gut microbiome composition of cecal contents was analyzed using 16S rRNA gene amplicon sequencing. Results: PSE supplementation improved glucose homeostasis (decreased serum insulin concentration, HOMA-IR, and HOMA-B) and reduced hepatic lipidosis in diabetic mice. PSE supplementation reversed DM-induced shifts in the relative abundance of amplicon sequence variants of Enterorhabdus, Staphylococcus, Anaerotruncus, and Akkermansia. Relative to the DM mice, the PSE group had suppressed gene expression levels of Cd8α, Csf2, and Irf23 and increased expression levels of Tyk2, Myd88, and Gusb in the liver. Conclusions: This study demonstrates that PSE supplementation improves T2DM-associated disorders of diabetic mice, in part due to the suppression of innate immune inflammation. Full article

Water exists in the beginning and hydrates all matter. Life emerged in water, requiring three essential components in compartmentalized spaces: (1) universal energy sources driving biochemical reactions and processes, (2) molecules that store, encode, and transmit information, and (3) functional players carrying out biological activities and structural organization. Phosphorus has been selected to create adenosine triphosphate (ATP) as the universal energy currency, nucleic acids for genetic information storage and transmission, and phospholipids for cellular compartmentalization. Meanwhile, proteins composed of 20 α-amino acids have evolved into extremely diverse three-dimensional forms, including folded domains, intrinsically disordered regions (IDRs), and membrane-bound forms, to fulfill functional and structural roles. This review examines several unique findings: (1) insoluble proteins, including membrane proteins, can become solubilized in unsalted water, while folded cytosolic proteins can acquire membrane-inserting capacity; (2) Hofmeister salts affect protein stability by targeting hydration; (3) ATP biphasically modulates liquid–liquid phase separation (LLPS) of IDRs; (4) ATP antagonizes crowding-induced protein destabilization; and (5) ATP and triphosphates have the highest efficiency in inducing protein folding. These findings imply the following: (1) hydration might be encoded in protein sequences, central to manifestation and modulation of protein structures, dynamics, and functionalities; (2) phosphate anions have a unique capacity in enhancing μs-ms protein dynamics, likely through ionic state exchanges in the hydration shell, underpinning ATP, polyphosphate, and nucleic acids as molecular chaperones for protein folding; and (3) ATP, by linking triphosphate with adenosine, has acquired the capacity to spacetime-specifically release energy and modulate protein hydration, thus possessing myriad energy-dependent and -independent functions. In light of the success of AlphaFolds in accurately predicting protein structures by neural networks that store information as distributed patterns across nodes, a fundamental question arises: Could cellular networks also handle information similarly but with more intricate coding, diverse topological architectures, and spacetime-specific ATP energy supply in membrane-compartmentalized aqueous environments? Full article

Background/Objectives: Palatability significantly influences food consumption, often leading to overeating and obesity by activating the brain’s reward systems. The nucleus accumbens (NAc) plays a central role in this process, modulating reward mechanisms primarily via dopamine through D2-like receptors (D2R, D3R, D4R). While the involvement of D2 receptors in feeding is well-documented, the role of D4 receptors (D4Rs) is less clear. Methods: Male Wistar rats received intra-NAc shell microinjections of the D4R agonist PD-168077 and the antagonist L-745870. This study also examined the modulation between D4R and glutamatergic transmission by administration of NMDA, NMDA receptor antagonist AP-5, AMPA, and AMPA receptor antagonist CNQX. Results: PD-168077 increased sweet solution intake by 46%, an effect that was reversed by L-745870. Pre-treatment with NMDA prevented the stimulatory effect of PD-168077, whereas the NMDA receptor antagonist AP-5 had no such effect. Additionally, AMPA administration reduced sweet solution intake by 63%, counteracting the effect of PD-168077, while the AMPA receptor antagonist CNQX, on its own, increased intake by 40%. Conclusions: These findings suggest that D4Rs promote hedonic feeding by modulating glutamatergic transmission in the NAc shell, highlighting the complexity of D4R involvement in food intake regulation. This study underscores the potential of targeting D4Rs for therapeutic interventions in eating disorders and obesity, though further research is essential to clarify the precise mechanisms through which D4R modulates AMPA and NMDA receptor activity in feeding behavior. Full article