Search Results (199)

Dissolvable microneedles (DMNs) represent an innovative approach to patient-friendly drug delivery, eliminating the need for conventional hypodermic injections. This study reports on the fabrication, Confocal Laser Scanning Microscopy (CLSM)-based optical visualization of drug distribution, and mechanical characterization of maltose-based DMNs impregnated with lignocaine, a local anesthetic. Microneedles were fabricated using a micro-molding technique and dried for nine hours. Structural integrity was evaluated using Field Emission Scanning Electron Microscopy (FESEM); drug distribution was examined via CLSM; and mechanical strength was assessed using nanoindentation. The FESEM results showed uniform microneedle formation with sharp tips and smooth surfaces, averaging 435 µm in height and 116 µm in width, with no significant dimensional variability (p > 0.5). CLSM analysis indicated even distribution of lignocaine throughout the matrix. Mechanical testing showed that each microneedle withstood 0.6 N, surpassing the 0.1 N threshold required for skin insertion. These results support the viability of maltose-based DMNs for local anesthetic delivery, with implications for outpatient, pediatric, and self-administered care settings. Future investigations will include Franz diffusion and in vitro dissolution studies to examine release kinetics. Full article

Carbon-fiber-reinforced thermoset polyimide composites have found wide applications in various aerospace areas. In this paper, the influence of carbon-fiber sizing on the thermal properties of polyimide composites was studied. Nonlinear detriment of the epoxy sizing was found to affect the composite’s thermal resistance. Furtherly, the mechanism, possibly responsible for the nonlinear detrimental effect of the epoxy sizing, was investigated through curing kinetics analysis and chemical structure characterization. Thermal curing activation energy change was found, possibly arising from the insertion of a flexible segment into the polyimide chain by epoxy–amine reaction. Based on the proposed mechanism, a strategy to manipulate the thermal resistance was established and verified. By the precuring of the carbon-fiber sizing, the polyimide composite exhibited obvious thermal resistance improvement, indicated by an enhancement of the glass transition temperature by 20 °C, and a weight-loss reduction under thermal aging at 400 °C by 25%. Simultaneously, a good fiber-matrix interface was maintained. This strategy provides a new route to enhance the thermal properties of polyimide composites from the viewpoint of carbon-fiber-matrix compatibility. Full article

Powered by high-efficiency thermophotovoltaics and developed through economics-by-design analysis, a promising, optimized design was selected for the radiantly integrated TPV–microreactor system. However, the novelty of the conversion system, the connection between the TPV and critical reactor core, requires a proper degree of reliability analysis to develop confidence in this technology. This is made difficult by the lack of computational tools that capture the full suite of physics and feedback mechanisms present in the RITMS design. This paper outlines the methods utilized to capture power, temperature, and reactivity variation and feedback mechanisms through time, utilizing lumped conditions, point kinetics equations, and the determination of temperature reactivity coefficients. The computational package was applied to a series of accident-driven transient scenarios, demonstrating the RITMS design’s ability to return to a safe operating equilibrium without active interference. In the case of high positive reactivity insertion accidents, design solutions were demonstrated that would mitigate risk. Full article

Influenza reporter viruses are essential for studying viral infection dynamics and assessing antiviral drug efficacy. However, insertion of exogenous reporter genes can impair both viral replication and reporter expression, limiting the development of these systems. In this study, CE1 compensatory mutation (G3A/C8U) was introduced into the 3′ non-coding region of the NS segment of influenza A/Puerto Rico/8/1934 using reverse genetics, generating the recombinant reporter virus H1N1-PR8-NS_CE1-mCherry. Compared with H1N1-PR8-NS_WT-mCherry, H1N1-PR8-NS_CE1-mCherry produced approximately 2.7-fold more infectious particles. CE1 compensatory mutation partially restored impaired replication kinetics in vitro, as evidenced by higher titers of H1N1-PR8-NS_CE1-mCherry at 48 h post-infection in MDCK cells. Additionally, H1N1-PR8-NS_CE1-mCherry maintained the intact mCherry gene insertion and high viral titers during serial passaging. Additionally, a real-time, non-invasive in vivo imaging of influenza A viruses was established using H1N1-PR8-NS_CE1-mCherry. A significant correlation was observed between lung fluorescence intensity and viral load, indicating that fluorescence signals serve as a reliable indicator of lung viral load in infected mice. Finally, utility of this model for in vivo drug screening was confirmed by antiviral drug oseltamivir phosphate. Above all, H1N1-PR8-NS_CE1-mCherry provides a tool for visualizing influenza A virus infection and evaluating antiviral drug efficacy. Full article

Silicon anodes have attracted considerable attention as next-generation lithium-ion battery materials owing to their exceptionally high theoretical capacity. However, their practical application remains limited by severe volume fluctuations during cycling, which lead to rapid capacity fading. In this work, a Si@SiC@ epitaxial Graphene (EG) core–shell nanocomposite is constructed through in situ epitaxial growth to overcome these challenges. The SiC interlayer functions as a robust mechanical buffer, accommodating the volume expansion of silicon during lithiation and delithiation, while the external graphene shell offers high electronic conductivity, structural resilience, and may provide additional Li⁺ storage sites. Structural and electrochemical characterizations, including ex situ X-ray diffraction, in situ Raman spectroscopy, and ex situ X-ray photoelectron spectroscopy, verify the reversible Li⁺ insertion/extraction and the preservation of structural integrity without phase collapse. The Si@SiC@EG anode delivers a high reversible capacity of 1747 mAh g⁻¹ at 0.1 A g⁻¹, outstanding rate performance, and remarkable durability, maintaining 872 mAh g⁻¹ after 2000 cycles at 1 A g⁻¹. Density functional theory calculations further indicate that strong interfacial coupling effectively lowers Li⁺ migration barriers, thereby improving ion transport kinetics. These findings highlight the potential of the Si@SiC@EG heterostructure as a viable platform for high-energy-density lithium-ion storage. Full article

Background: Digital light processing (DLP) 3D printing has emerged as a rapid alternative to labour-intensive micro-moulding for producing microneedle (MN) arrays, yet its use in biodegradable, dissolving MNs has been limited by proprietary, non-degradable resins. Methods: The current study proposed an innovative, biocompatible PEGDA–vinyl-pyrrolidone photo-resin with lithium phenyl(2,4,6-trimethylbenzoyl) phosphinate initiator, which systematically optimises its rheology and photo-reactivity for DLP printing. Resin formulations were evaluated through viscosity profiling, cure kinetics, FTIR, and ¹H NMR, and MN arrays were printed using a desktop DLP platform and characterised by optical microscopy, mechanical testing, thermal analysis, and dissolution studies. Results: A 40% PEGDA up-to 100% VP blend with 0.4% initiator was identified as providing rapid photopolymerisation, low shrinkage and complete vinyl conversion. Using a desktop DLP platform, 6 × 6 MN patches were printed in a single step without moulds and analysed by optical and scanning electron microscopy. The printed MNs reproduced CAD dimensions with <3% deviation, achieving a height of 1.40 ± 0.02 mm and a base thickness of 1.00 ± 0.01 mm, and showed a tip radius consistent with sharp penetration. Compression testing measured an array force of 32 N, corresponding to ~0.9 N per needle, exceeding the 0.2 N threshold for skin insertion. FTIR and ¹H NMR confirmed near-quantitative crosslinking, thermogravimetric and differential scanning calorimetry indicated stability at ambient conditions, and dissolution studies showed complete needle dissolution. Conclusions: An optimised PEGDA/VP resin yields geometrically precise, mechanically robust dissolving MNs in a single step, addressing the limitations of micro-moulding and paving the way for customisable, on-demand transdermal delivery of active molecules and biologics. Full article

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

Polyproline residues are well known to induce ribosomal stalling during translation. Our previous work demonstrated that inserting a short translation-enhancing peptide, Ser-Lys-Ile-Lys (SKIK), immediately upstream of such difficult-to-translate sequences can significantly alleviate ribosomal stalling in Escherichia coli. In this study, we provide a quantitative evaluation of its translational effect by kinetically analyzing the influence of the SKIK peptide on polyproline motifs using a reconstituted E. coli in vitro translation system. Translation rates estimated under reasonable assumptions fitted well to a Hill equation within a Michaelis–Menten-like kinetic framework. We further revealed that repetition of the SKIK tag did not provide any positive effect on translation. Moreover, introduction of the SKIK tag increased the production of polyproline-containing proteins, including human interleukin 11, human G protein signaling modulator 3, and DUF58 domain–containing protein from Streptomyces sp. in E. coli cell-free protein synthesis. These findings not only provide new insight into the fundamental regulation of translation by nascent peptides but also demonstrate the potential of the SKIK peptide as a practical tool for synthetic biology, offering a strategy to improve the production of difficult-to-express proteins. Full article

Rechargeable aqueous Zn-MnO₂ batteries are positioned as a highly promising candidate for next-generation energy storage, owing to their compelling combination of economic viability, inherent safety, exceptional capacity (with a theoretical value of ≈308 mAh·g⁻¹), and eco-sustainability. However, this system still faces multiple critical challenges that hinder its practical application, primarily including the ambiguous energy storage reaction mechanism (e.g., unresolved debates on core issues such as ion transport pathways and phase transition kinetics), dendrite growth and side reactions (e.g., the hydrogen evolution reaction and corrosion reaction) on the metallic Zn anode, inadequate intrinsic electrical conductivity of MnO₂ cathodes (≈10⁻⁵ S·cm⁻¹), active material dissolution, and structural collapse. This review begins by systematically summarizing the prevailing theoretical models that describe the energy storage reactions in Zn-Mn batteries, categorizing them into the Zn²⁺ insertion/extraction model, the conversion reaction involving MnO_x dissolution–deposition, and the hybrid mechanism of H⁺/Zn²⁺ co-intercalation. Subsequently, we present a comprehensive discussion on Zn anode protection strategies, such as surface protective layer construction, 3D structure design, and electrolyte additive regulation. Furthermore, we focus on analyzing the performance optimization strategies for MnO₂ cathodes, covering key pathways including metal ion doping (e.g., introduction of heteroions such as Al³⁺ and Ni²⁺), defect engineering (oxygen vacancy/cation vacancy regulation), structural topology optimization (layered/tunnel-type structure design), and composite modification with high-conductivity substrates (e.g., carbon nanotubes and graphene). Therefore, this review aims to establish a theoretical foundation and offer practical guidance for advancing both fundamental research and practical engineering of Zn-manganese oxide secondary batteries. Full article

The hydroesterification of olefins provides a highly efficient way to produce high value-added ester products from simple and abundant olefin feedstocks. In this work, DFT calculation was performed to investigate the detailed reaction mechanism of propene hydroesterification over Rh(II)/Silicalite-2 catalysts. Three possible mechanistic pathways were systematically explored and compared in terms of their adsorption configurations, reaction energies, and transition-state barriers. Among them, the Carbonylation-First pathway exhibited the most favorable energy profile with the lowest overall kinetic barriers, indicating it to be the most likely way for ester formation. A comparison of methyl butyrate and methyl isobutyrate formation revealed that the linear product is energetically more favorable, particularly along the Carbonylation-First pathway. Moreover, the Rh(II) center demonstrates a different catalytic effect over conventional Rh(I) species by significantly lowering the energy barrier for CO insertion, a key step in both hydroformylation and hydroesterification. These findings provide fundamental insight into the role of Rh(II)/zeolite systems in carbonylation reactions and offer theoretical guidance for the design of catalysts. Full article

The self-consistent field Poisson–Boltzmann framework is applied for analysis of equilibrium partitioning of ampholytic protein-like nanocolloids between buffer solution and weak (pH-sensitive) versus strong polyelectrolyte (polyanionic) brushes with the same net charge per unit area. The position-dependent nanocolloid net charge and the insertion freeenergy profiles are derived as a function of pH and ionic strength in the solution. It is demonstrated that, similar to strong polyelectrolyte brushes, pH-sensitive brushes are capable of the uptake of nanocolloids in the vicinity of the isoelectric point, that is, when the net charge of the colloid in the buffer has either the opposite or the same sign as the ionized monomer units of the brush. At $pI\ge p{K}_{brush}$ and $pH\ge pI$, the particle absorption patterns by similarly (negatively) charged brushes are qualitatively similar in the cases of strong and weak polyelectrolyte brushes, but the freeenergy barrier at the brush periphery is wider for weak than for strong polyelectrolyte brushes, which may cause stronger kinetic hindrance for the nanocolloid uptake by the brush. A decrease in $pH$ below the IEP leads to a monotonic increase in the depth of the insertion freeenergy minimum inside a strong polyelectrolyte brush, whereas for weak polyelectrolyte brushes, a more peculiar trend is predicted: due to competition between the increasing positive charge of the nanocolloid and the decreasing magnitude of the negative charge of the brush, the absorption is weakened at low $pH$. Full article

The development of simple and yet accurate formulations of frequency–amplitude relationships for non-conservative nonlinear oscillators is an important issue. The present paper is concerned with integral-type frequency–amplitude formulas in the dimensionless time domain and time domain to accurately determine vibrational frequencies of nonlinear oscillators. The novel formulation is a balance of kinetic energy and the work during motion of the nonlinear oscillator within one period; its generalized formulation permits a weight function to appear in the integral formula. The exact values of frequencies can be obtained when exact solutions are inserted into the formulas. In general, the exact solution is not available; hence, low-order periodic functions as trial solutions are inserted into the formulas to obtain approximate values of true frequencies. For conservative nonlinear oscillators, a powerful technique is developed in terms of a weighted integral formula in the spatial domain, which is directly derived from the governing ordinary differential equation (ODE) multiplied by a weight function, and integrating the resulting equation after inserting a general trial ODE to acquire accurate frequency. The free parameter is involved in the frequency–amplitude formula, whose optimal value is achieved by minimizing the absolute error to fulfill the periodicity conditions. Several examples involving two typical non-conservative nonlinear oscillators are explored to display the effectiveness and accuracy of the proposed integral-type formulations. Full article

Introduction: Two-stage revision with an antibiotic-loaded, temporary static cement spacer is a common treatment for periprosthetic joint infection (PJI) of the knee. However, limited data exists on in vivo antibiotic elution kinetics after spacer implantation. This pilot study uses the technique of microdialysis (MD) to collect intra-articular knee samples. The aim was to evaluate MD as an intra-articular sampling method to detect spacer-eluted antibiotics within 72 h after surgery and to determine whether they show specific elution kinetics. Methods: Ten patients (six male, four female; age median 71.5 years) undergoing two-stage revision for knee PJI were included. A MD catheter was inserted into the joint during explantation of the infected inlying implant and implantation of a custom-made static spacer coated with COPAL cement (0.5 g gentamicin (G) and 2 g vancomycin (V)). Over 72 h postoperatively, samples were collected and analyzed for spacer-eluted antibiotics, intravenously administered antibiotics (e.g., cefazolin and cefuroxime), metabolic markers (glucose and lactate), and Interleukin-6 (IL-6). Local and systemic levels were compared. Results: All catheters were positioned successfully and well tolerated for 72 h. Antibiotic concentrations in MD samples peaked within the first 24 h (G: median 9.55 µg/mL [95% CI: 0.4–17.36]; V: 37.57 µg/mL [95% CI: 3.26–81.6]) and decreased significantly over 72 h (for both p < 0.05, G: 4.27 µg/mL [95% CI: 2.26–7.2]; V: 9.69 µg/mL [95% CI: 3.86–24]). MD concentrations consistently exceeded blood levels (p < 0.05), while intravenously administered antibiotics showed higher blood concentrations. Glucose in MD samples decreased from 17.71 mg/dL to 0.89 mg/dL (p < 0.05). IL-6 and lactate concentrations showed no difference between MD and blood samples. Conclusions: Monitoring antibiotics eluted by a static spacer with intra-articular MD for 72 h is feasible. Gentamicin and vancomycin levels remained above the minimal inhibitory concentration. Differentiating infection from surgical response using metabolic and immunological markers remains challenging. Prolonged in vivo studies with MD are required to evaluate extended antibiotic release in two-stage exchanges. Full article

Niacinamide was recently shown to directly interact with bacterial DNA and interfere with cell replication; niacinamide mode of interaction and efficacy as a natural anti-microbial molecule were also described. The aim of this study is to elucidate the exact binding mechanism of niacinamide to microbial DNA. Intercalation is a binding mode where a small planar molecule, such as niacinamide, is inserted between base pairs, causing structural changes in the DNA. Melting curve analysis with various intercalating dyes demonstrated that niacinamide interaction with bacterial DNA reduces its melting temperature in a linear dose-dependent manner. Niacinamide’s effect on the melting temperature was found to be % GC-dependent, while purine stretches were also found to influence the binding kinetics. Finally, fluorescent intercalator displacement (FID) assays demonstrated that niacinamide strongly reduces SYBR Safe signal in a dose-dependent manner. Interestingly, competition assays with a minor groove binder also reduced Hoechst signal but in a non-linear manner, which can be attributed to strand lengthening and unwinding following niacinamide intercalation. Taken altogether; our results suggest a “disruptive intercalation” as the mode of interaction of niacinamide with bacterial DNA. Formation of locally destabilized DNA portions by niacinamide might interfere with protein–DNA interaction and potentially affect several crucial bacterial cellular processes, e.g., DNA repair and replication, subsequently leading to cell death. Full article

Prussian blue and its analogs (PBAs), considered potential cathode materials for sodium-ion batteries (SIBs), still confront multiple challenges. For example, many defect vacancies and high crystal water content are generated during the fast crystallization of PBAs, impairing the rate performance. The stress accumulation during Na⁺ insertion/extraction destabilizes the lattice framework and then damages the electrochemical performance. Herein, iron-based Prussian blue with an open-pore skeleton structure (PB-3) is prepared using a facile template method which employs PVP and sodium citrate to control the crystallization rate and adjust the particle morphology. The prepared materials exhibit excellent kinetic properties and are conducive to mitigate the volume changes during ion insertion/extraction processes. PB-3 electrode not only exhibits a superior rate performance (92 mAh g⁻¹ reversible capacity at 2000 mA g⁻¹), but also presents superior cycling performance (capacity retention remained at 90.2% after 600 cycles at a current density of 500 mA g⁻¹). The highly reversible sodium ion insertion/extraction mechanism of PB-3 is investigated by ex situ XRD tests, which proves that the stabilized lattice structure can enhance the long cycling performance. In addition, the considerable capacitance contributes to the rate performance. This study provides valuable insights for the subsequent development of high-performance and stable cathodes for SIBs. Full article