Search Results (8,242)

This study reports the fabrication of chitosan/carboxymethyl cellulose (C/M) nanocomposites by electrolyte gelation–spray drying and the evaluation of their antibacterial performance as carriers for the antibiotic ampicillin. Chitosan (C), a cationic biopolymer derived from chitin, was combined with the anionic polysaccharide carboxymethyl cellulose (M) at different mass ratios to form stable nanocomposites via electrostatic interactions and then collected in a spray dryer. The resulting particles exhibited mean diameters ranging from 800 to 1500 nm and zeta potentials varying from +90 to −40 mV, depending on the C/M ratio. The optimal formulation (C/M = 2:1 ratio) achieved a high recovery yield (71.1%), lower PDI (0.52), and ampicillin encapsulation efficiency EE (82.4%). Fourier transform infrared spectroscopy (FTIR) confirmed the presence of hydrogen bonding and ionic interactions among C/M, and ampicillin within the nanocomposite matrix. The nanocomposites demonstrated controlled ampicillin release and pronounced antibacterial activity against Staphylococcus aureus, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 3.2 µg/mL and 5.3 µg/mL, respectively, which were lower than those of free ampicillin. These results indicate that the chitosan/carboxymethyl cellulose nanocomposites are promising, eco-friendly carriers for antibiotic delivery and antibacterial applications. Full article

Cemented paste backfill (CPB) is widely used in mining operations to enhance underground stope stability, production, and safety. Accurately predicting paste flow behaviours in backfill reticulation circuits is crucial for efficient delivery control and asset longevity. However, the predictions remain challenging due to complex rheology and flow-induced particle heterogeneities of CPB. This study develops a computational fluid dynamics (CFD)-based analysis framework to investigate flow dynamics of the CPB and the wear conditions of the pipes, considering slip layer and shear-induced particle migration. Experimental loop tests are conducted to measure pressure drops of CPB at different velocities, providing data for validating the developed CFD model. Simulation results are in good agreement with the measured pressure drops and wear rates of the internal pipeline wall. Furthermore, comparisons with existing models indicate that the developed model provides more accurate predictions. Microscopical analyses reveal that shear-induced particle migration leads to the formation of a distinct plug flow region, with particles accumulating near the unyielded boundary. Meanwhile, a low particle concentration near the pipe wall reduces local viscosity and pressure drop. Parametric studies reveal that increased flow velocity and reduced pipe diameter significantly elevate both pressure drop and wear rate, while higher solid concentrations induce nonlinear rheological effects. Full article

Bacteriophages, or phages, are viruses that specifically infect and lyse bacterial cells. Since their discovery 110 years ago, they have held a unique place in microbiology, medicine, and agriculture as both scientific tools and potential therapeutic agents. The concept of employing phages to combat bacterial infections, known as phage therapy, predates the antibiotic era and has undergone cycles of enthusiasm, neglect, and revival. Initially explored in the early 20th century, phage therapy offered a targeted biological approach to bacterial disease control. However, the widespread adoption of antibiotics led to a significant reduction in phage research, which only regained momentum in recent decades owing to the global rise of antibiotic-resistant bacteria and increasing demand for environmentally sustainable disease management strategies. This review traces the complete timeline of this history, highlighting key milestones in phage discovery, molecular microbiology, the antibiotic era, and the resulting critical events that spurred the modern phage renaissance in plant disease management. Finally, the significance of cutting-edge integration of synthetic biology, advanced phage delivery systems, and artificial intelligence (AI), which could drive the development of next-generation biopesticides, is also discussed. Full article

Background/Objectives: Older adults often face nutrition challenges due to mobility issues, chronic conditions, and limited access to adequate nutrition. Digital and technology-based interventions, including those with nutrition education, nutrition counseling and Medically Tailored Meals [MTMs], can help address these barriers. However, the extent and characteristics of such programs in the United States remain unclear. This scoping review aimed to map the existing evidence on digital and technology-based (“digi-tech”) nutrition interventions for older adults in the United States, with particular attention to the presence, characteristics, and gaps related to MTMs. Methods: This scoping review followed the PRISMA-ScR framework to map existing evidence on technology-enabled nutrition care interventions for older adults aged ≥ 60 years in the United States. Systematic searches were conducted across multiple databases, yielding 18,177 records. Following title and abstract screening, full-text review, and eligibility assessment, 16 intervention studies were included. Study designs comprised randomized controlled trials, quasi-experimental and non-randomized studies, mixed-methods feasibility studies, pilot studies, and one retrospective longitudinal cohort study. Data were extracted on study design, population characteristics, intervention components, technology modalities, outcomes, feasibility, acceptability, and reported barriers. Results: Interventions varied in duration [8 weeks to ≥12 months] and content. Foci ranged from remote nutrition education and mobile app-based tracking to multicomponent interventions integrating exercise, nutrition counseling, health literacy, and meal delivery. Telehealth was the most commonly used technology modality, followed by mobile health applications, wearable devices, and online educational platforms. Most interventions reported high feasibility and acceptability, with improvements in diet quality, adherence to healthy eating patterns, clinical measures such as HbA1c and blood pressure, and functional performance. Common implementation barriers included declining technology use over time, digi-tech literacy, and access to devices or the internet. Notably, no studies evaluated a digi-tech-based MTMs intervention exclusively for older adults in the U.S. Conclusions: Digital and technology-based nutrition interventions show promise for improving dietary and health outcomes in older adults, but there is insufficient empirical evidence. Future research might develop and evaluate hybrid digi-tech intervention models that leverage the potential of digi-tech tools while addressing barriers to technology adoption among older adults. Full article

The rhesus macaque (Macaca mulatta) is a valuable model for pregnancy research due to its physiological similarity to humans and the ability to conduct studies in a controlled environment. Our previous work used non-invasive imaging methods to assess placental hemodynamics across gestation with correlative tissue analysis post-delivery. Here, we expand access to longitudinal timepoints from ongoing pregnancies by obtaining placental biopsies using ultrasound-guided needle aspiration. This approach aligns with New Approach Methods (NAMs) and supports animal welfare by reducing the number of animals required. We describe a chorionic villus sampling (CVS) simulation model which facilitates training to gain proficiency in technical skills prior to performing the procedure on animals. We report outcomes from three rhesus macaques that underwent CVS three times between gestational days 40 to 106 (term: 165 days). Although biopsy samples are smaller than whole placenta, tissue yields were sufficient for multiple uses. We demonstrate (1) appropriate histology from aspirated samples, (2) good RNA quality and yield, and (3) the ability to isolate trophoblast organoids, an advancement in NAMs that reduces the need for first-trimester surgical delivery. No spontaneous preterm delivery occurred following serial CVS procedures, supporting the use of this sampling method to maximize animal utilization in longitudinal pregnancy studies. Full article

Background: Caffeine (CAF), whether extracted from plants or synthesised as a chemical compound, is considered the safest among other xanthine alkaloids. Novel nano-cream formulations have been successfully developed and evaluated to increase the potential of caffeine as a skin cosmeceutical, targeting the minimisation of cellulite appearance. Methods: Nano-cream formulations were prepared through a process of hot-temperature emulsification, in a variety of homogeniser combinations. Results: When chemical penetration enhancers (CPEs) (lanolin, transcutol, and propylene glycol), either alone or in combination, were incorporated into the nano-cream formulations, the permeation of CAF through skin increased. All nano-cream formulations achieved sustained delivery of CAF into and through the skin over 8 h (IVPT). Quantification of CAF from skin tissues was achieved using high-performance liquid chromatography (HPLC). The nano-cream formulation containing lanolin (LAN) showed the highest CAF permeation (8.829 ± 1.472 µg/cm²/h) through the skin compared to CAF in an aqueous solution (2.533 ± 0.480 µg/cm²/h) and a commercial CAF cellulite product with the same CAF concentration (2.827 ± 0.555 µg/cm²/h). Therefore, 2% CAF nano-cream formulation containing LAN was chosen for clinical testing. A double-blind, randomised, placebo-controlled paired trial was conducted, in which each volunteer applied active and placebo creams to the upper thighs twice daily for 12 weeks. The effect of the cream on skin appearance was monitored over 12 weeks. The primary outcome measures were reduced cellulite scores from 3.96 (95% CI: 3.16–4.76) to 2.50 (95% CI: 1.70–3.30) (active) compared with placebo from 3.88 (95% CI: 3.08–4.67) to 2.83 (95% CI: 2.03–3.63). The effect sizes (E.S.) indicated a moderate effect for the active CAF nano-cream formulation (E.S. = 0.475), while the placebo (E.S. = 0.286) had a small effect. Conclusion: We concluded that our optimised 2% CAF nano-cream formulation containing LAN offered an effective formulation strategy for enhancing skin penetration in the IVPT study. The LAN nano-cream formulation demonstrated efficacy and tolerability, both objectively and subjectively, in a human clinical trial. Full article

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article

Curling presents a challenging continuous-control problem in which shot outcomes depend on long-horizon interactions between complex physical dynamics, strategic intent, and opponent responses. Despite recent progress in applying reinforcement learning (RL) to games and sports, curling lacks a unified environment that jointly supports stable, rule-consistent simulation, structured state abstraction, and scalable agent training. To address this gap, we introduce a comprehensive learning framework for curling AI, consisting of a full-sized simulation environment, a task-aligned Markov decision process (MDP) formulation, and a two-phase training strategy designed for stable long-horizon optimization. First, we propose a novel MDP formulation that incorporates stone configuration, game context, and dynamic scoring factors, enabling an RL agent to reason simultaneously about physical feasibility and strategic desirability. Second, we present a two-phase curriculum learning procedure that significantly improves sample efficiency: Phase 1 trains the agent to master delivery mechanics by rewarding accurate placement around the tee line, while Phase 2 transitions to strategic learning with score-based rewards that encourage offensive and defensive planning. This staged training stabilizes policy learning and reduces the difficulty of direct exploration in the full curling action space. We integrate this MDP and training procedure into a unified Curling RL Framework, built upon a custom simulator designed for stability, reproducibility, and efficient RL training and a self-play mechanism tailored for strategic decision-making. Agent policies are optimized using Soft Actor–Critic (SAC), an entropy-regularized off-policy algorithm designed for continuous control. As a case study, we compare the learned agent’s shot patterns with elite match records from the men’s division of the Le Gruyère AOP European Curling Championships 2023, using 6512 extracted shot images. Experimental results demonstrate that the proposed framework learns diverse, human-like curling shots and outperforms ablated variants across both learning curves and head-to-head evaluations. Beyond curling, our framework provides a principled template for developing RL agents in physics-driven, strategy-intensive sports environments. Full article

Background: To overcome the gastrointestinal and hepatic toxicity of oral pirfenidone (PFD) in the treatment of idiopathic pulmonary fibrosis (IPF), this study systematically constructed a minimal-component, buffer-free pirfenidone aerosol inhalation solution (PFD-AIS), achieving lung-targeted delivery, reduced systemic exposure, and maintained antifibrotic efficacy. Methods: Analytical methods for PFD-AIS, covering content, related substances, aerodynamic particle size distribution (APSD), and delivered dose uniformity, were established. The prescription and preparation process of the formulation was optimized by evaluating its key quality attributes. Pharmacodynamic and pharmacokinetic evaluations of PFD-AIS were performed in a mouse lung-fibrosis model and SD rats. Results: The final specification of PFD-AIS was set to 40 mg:4 mL, containing 40 mg of PFD, 28 mg of sodium chloride, and 4 mL of injection water with a preparation process of 40 °C for 60 min and a pH range of 4–8. The PFD-AIS exhibited a fine particle fraction (FPF) of 56.1%, meeting the requirements for deep lung deposition. The delivered dose and delivery rate were 17.52 mg and 2.48 mg/min, respectively, both complying with inhalation formulation standards. In the bleomycin-induced IPF mouse model, the PFD-AIS markedly improved pulmonary fibrosis pathology, reduced the lung coefficient, and significantly lowered serum ALT/AST levels, indicating hepatic protection. In the SD rats, compared with oral dosing, PFD-AIS administration resulted in significantly lower AUC_0−t (−63%) and AUC_0–∞ (−67%) values, demonstrating a substantial reduction in systemic drug exposure. Conclusion: This work presents a complete, systematic chain—from formulation, process, and quality control to pharmacodynamics and pharmacokinetics—of a PFD-AIS. The PFD-AIS is effective and feasible, featuring a stable preparation process and controllable quality. Lung-directed drug delivery enhances PFD’s therapeutic efficacy, reduces systemic exposure and liver toxicity, and offers significant clinical advantages. Full article

Peripheral artery disease (PAD) remains a great threat to the health of older people globally. Nitric oxide (NO), as an important signaling molecule, is integral to processes such as angiogenesis, inflammation, and tissue regeneration, making it a potential candidate for PAD treatment. Nevertheless, NO—based therapies are frequently limited in clinical utility, primarily due to the lack of effective strategies for fine-tuning the release of exogenous NO. In this study, we developed an enzyme—prodrug pair based on endocellulase (Cel5A-h38), which ensured complete bioorthogonality, thus avoiding interference with endogenous enzymes and eliciting an inflammatory response. This delivery system enables localized and controlled NO release, thus preventing side effects induced by systemic exposure. The therapeutic efficacy of the NO delivery system was systematically evaluated in a porcine model of hindlimb ischemia. Our results confirmed the benefits of targeted NO delivery in hindlimb ischemia, which include enhanced neovascularization and tissue perfusion, reduced inflammation, and alleviated muscle fibrosis, demonstrating its optimal translational potential. Full article

Spine stereotactic radiotherapy and radiosurgery (SSRS) techniques, encompassing both fractionated stereotactic treatments and single-fraction radiosurgery, are widely used for the management of spinal metastases due to their ability to deliver highly conformal radiation while limiting dose to adjacent critical structures. Clinical outcomes following SSRS, including durable local control and acceptable toxicity, have been reported previously in multiple institutional series. In this manuscript, we describe the clinical workflow used to deliver SSRS at a high-volume academic center, with emphasis on the medical physics processes that support routine clinical practice. Key elements of the workflow include patient selection, treatment region-specific immobilization, CT and MRI-based simulation, treatment planning, patient-specific quality assurance, and image-guided treatment delivery. Rather than presenting new outcome data, this work provides a descriptive overview of how established SSRS techniques are integrated into day-to-day clinical care. Full article

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

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

High-energy methods dominate the development of lipid nanoparticles but often require specialized equipment that increases production costs. Low-energy approaches, particularly those free of organic solvents, offer a promising alternative. This study aimed to obtain nanostructured lipid carriers (NLCs) using a solvent-free, low-energy process combining microemulsification and phase inversion. Cetearyl alcohol and PEG-40 hydrogenated castor oil were selected as the solid lipid and surfactant, respectively; the formulation and process were optimized through a Box–Behnken Design. Incorporation of the ionic surfactant extended colloidal stability, while the poloxamer in the aqueous phase enhanced steric stabilization. Resveratrol was efficiently encapsulated (E.E. = 98%), contributing to reduced particle size (291 nm), improved homogeneity (PDI = 0.25), and positive surface charge (+43 mV). Scale-up yielded stable particles carrying resveratrol with a mean size of 507 nm, PDI = 0.24, and ZP = +52 mV. The optimized formulation remained stable for 90 days at 8 °C. In vitro release demonstrated a sustained and controlled release profile, with significantly lower resveratrol release compared to the free compound. Thermal analysis confirmed drug incorporation within the lipid matrix, while transmission electron microscopy (TEM) revealed spherical particles (~200 nm) and SAXS indicated a nanostructure of ~50 nm. Overall, this study demonstrates that solvent-free, low-energy processing can produce stable and scalable NLC formulations, successfully encapsulating resveratrol with favorable physicochemical properties and controlled release behavior. These findings highlight a simple, cost-effective strategy for developing lipid-based nanocarriers with potential applications in drug delivery. Full article

Needle-free injection (NFI) technology is a promising alternative to conventional syringe injection, as it mitigates needle-related complications and enhances patient compliance. However, achieving the controlled and efficient dispersion of larger-volume formulations (>1 mL) within tissues remains a significant challenge. This study presents a novel pneumatic NFI system that uses a two-phase driving mode to regulate driving pressure and duration with an ejection volume of 1.0–2.0 mL. The integrated pressure stabilization unit significantly reduces pressure fluctuations during the initial injection phase, generating a more stable and uniform spray distribution. It is designed to produce an ideal elliptical dispersion effect while eliminating splatter, enabling controlled large-volume delivery. Jet impact experiments were conducted to investigate the dynamic characteristics of microjets generated by conventional single-phase and novel two-phase driving modes. Furthermore, the influence of the driving mode on the dispersion behaviors of microjets in agarose gels was explored through high-speed imaging of gel injections. The results demonstrate that the two-phase driving mode produces a distinct two-phase jet pressure profile. Compared to the single-phase mode, the two-phase mode produced a significantly larger dispersion width at equivalent initial driving pressures. This promotes more uniform lateral drug distribution and achieves a higher percentage of liquid drug delivery in gels. Furthermore, favorable driving pressure combinations were identified for different volumes: (1.25–0.25) MPa for 1.0 mL, (1.25–0.50) MPa for 1.5 mL, and (1.50–0.50) MPa for 2.0 mL. This provides a practical basis for optimizing clinical parameters and advancing the development of controllable NFI systems. Full article