Search Results (981)

Objective: This retrospective cross–sectional study aimed to characterize HIV–1 genotypes, assess drug resistance, and analyze molecular transmission networks in Zhongwei City to inform prevention strategies. Methods: Plasma samples were collected from antiretroviral therapy (ART)–treated patients (2007–2024) with viral load ≥200 copies/mL. HIV–1 pol was amplified by nested PCR; successful sequences were genotyped by maximum likelihood (ML) (IQ–TREE, TVM+F+I+G4, 1000 bootstrap). Drug resistance (DR) was interpreted using Stanford HIV Drug Resistance Database (HIVDB) v9.0; detected mutations represent acquired drug resistance (ADR). Pairwise genetic distances (GD) (TN93 model) were calculated; transmission networks were constructed in Cytoscape 3.10.3. Results: 75 sequences were obtained. Males (84.00%), and heterosexual transmission (64.00%) predominated. CRF07_BC (46.67%) and CRF01_AE (38.67%) were the major subtypes; the overall ADR rate was 40.00%, mainly NNRTIs–associated (30.67% of all participants, including 16.00% single–class NNRTIs and 14.67% dual–class NRTIs–NNRTIs). Network inclusion rate was 40.00% of the 75 sequences; CRF07_BC showed higher betweenness centrality (p = 0.028), while CRF01_AE and CRF85_BC showed higher closeness centrality (p < 0.001). Occupation significantly affected network enrollment (p ≤ 0.05). Conclusion: HIV–1 subtypes are diverse with high ADR. CRF07_BC may act as a transmission bridge, whereas CRF01_AE and CRF85_BC exhibit faster potential spread. Baseline DR testing and network–guided interventions are recommended. Full article

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with poor outcomes in advanced stages and significant limitations in current chemotherapy regimens due to systemic toxicity. Extracellular vesicles (EVs) have emerged as promising natural drug delivery vehicles, offering the potential for targeted, less toxic therapies. This study investigates the feasibility of using autologous, patient-derived EVs as a delivery system for the chemotherapeutic agent doxorubicin, focusing on how disease stage and the EV protein corona influence loading and delivery efficiency. Methods: EVs were isolated from plasma and tissue samples of CRC patients at different disease stages, as well as from healthy controls, demonstrating successful isolation and characterisation of EVs, with distinct profiles across different sources. Results: Doxorubicin loading into EVs was significantly higher in CRC patient-derived EVs compared to healthy controls, and tissue-derived EVs yielded higher quantities of drug-loaded particles. Delivery of doxorubicin-loaded EVs to recipient CRC cell lines (SW480 and SW620) revealed that disease stage impacts both EV uptake and drug delivery, with late-stage EVs showing reduced uptake and delivery efficiency. The protein corona, known to coat circulating EVs, was found to influence drug loading and delivery. Pre-treatment of cell line-derived EVs with plasma proteins enhanced EV uptake but reduced doxorubicin loading and subsequent delivery, particularly when using plasma from healthy volunteers. Conclusions: These findings underscore the importance of EV source and protein corona composition in optimising drug delivery strategies. Our results suggest that autologous, patient-derived EVs hold potential as a targeted drug delivery system for CRC, but highlight the need for further optimisation of EV isolation, loading methods, and understanding of how disease progression affects EV functionality. This approach could ultimately reduce systemic toxicity and improve therapeutic outcomes for CRC patients. Full article

Background: 5q spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by progressive muscle weakness. Nusinersen, the first disease-modifying therapy for SMA, has demonstrated efficacy in both clinical trials and real-world studies. However, the precise timing of therapeutic onset following Nusinersen administration remains unclear. Methods: This retrospective study analyzed clinical data from patients with genetically confirmed 5q SMA who received Nusinersen treatment for at least six months at Peking University First Hospital. Motor function was assessed using standardized scales prior to each dose. Results: In total, 74 patients were screened, of whom 62 were enrolled, including 14 with type 1, 29 with type 2, and 19 with type 3 SMA. Thirty-two patients completed motor function assessments. After six months of treatment, 62.5% achieved a primary clinically meaningful response (an increase of ≥4 points in CHOP-INTEND or ≥3 points in HFMSE). Seven patients (21.9%) attained or regained motor milestones. Median improvements were 6 points in CHOP-INTEND (p = 0.001), 4 points in HFMSE (p = 0.003), and 1.5 points in RULM (p = 0.045). Further analysis indicated that the available median time to treatment response was approximately 2 months. In patients with severe scoliosis or prior spinal surgery, ultrasound-guided lumbar puncture demonstrated a high success rate (94.9%). Regarding safety, intrathecal injection-related adverse events occurred in eight patients (12.9%), and no adverse events led to treatment discontinuation. Conclusions: During the loading phase, Nusinersen provides clinical benefit for the majority of patients, with a median time to therapeutic response for monitoring of approximately 2 months. Ultrasound-guided intrathecal administration is the preferred approach for individuals with complicated spinal conditions. These findings may help guide clinical expectations for physicians, patients, and caregivers. Full article

Background: Uncontrolled hemorrhage, especially at non-compressible sites, remains a major cause of preventable trauma deaths. This study reports the development of fibrinogen-loaded calcium carbonate (CaCO₃) microparticles that combine hemostatic activity with self-propelling capability for targeted delivery against blood flow, with a focus on understanding formulation-dependent trade-offs among particle yield, protein loading, clotting performance, and transport behavior. Methods: Microparticles were synthesized via a precipitation method using different carbonate sources and characterized for yield, morphology, size, and fibrinogen encapsulation. Hemostatic function was assessed using rotational thromboelastometry (ROTEM) in fibrinogen-deficient plasma. Propulsion behavior was evaluated following exposure to protonated tranexamic acid (TXA⁺), which triggers CO₂ generation. Particle size and encapsulation were examined by microscopy and fluorescence imaging. Results: The precipitation method produced spherical micrometer-sized particles, with fibrinogen inclusion reducing yield and particle size relative to unload controls. Fluorescence microscopy confirmed successful encapsulation. Encapsulation efficiency varied with formulation, with sodium carbonate-based particles showing higher relative fibrinogen loading. ROTEM analysis demonstrated that fibrinogen-loaded particles significantly improved clot formation, increasing maximum clot firmness compared to fibrinogen-free particles, although performance remained formulation-dependent. TXA⁺-triggered propulsion achieved maximum speeds up to 4.221 cm/s. Fibrinogen-loaded particles exhibited longer activation lag times than unloaded particles, indicating a trade-off between hemostatic functionality and propulsion kinetics. Conclusions: Fibrinogen-loaded CaCO₃ microparticles exhibit both hemostatic activity and chemically triggered motion in vitro. The study identifies key formulation-dependent trade-offs between particle yield, fibrinogen loading, clotting performance, and propulsion behavior. While these findings support the feasibility of combining localization and clot stabilization mechanisms, further studies under physiologically relevant flow conditions and in vivo models are required to evaluate their potential for active delivery in non-compressible hemorrhage. Full article

Fast growth in electric vehicle (EV) charging stations is changing the way regional distribution networks are loaded. The difficulty is not only the size of the added demand, but also the fact that charging appears at different places, at different times, and under different voltage constraints. This paper considers the common planning situation in which station-level charging records are incomplete and only transformer-side aggregate measurements are available. A data-driven hosting capacity (HC) assessment method is developed for this setting. The method first constructs zone-specific daily load profiles and then separates EV charging components from mixed transformer curves through an improved ISODATA clustering method and an improved genetic algorithm (IGA). For planned electric vehicle charging stations (EVCSs) without historical measurements, Ordinary Kriging (OK) is used to infer charging profiles from nearby observed stations in the same functional zone. The calculated HC is then checked successively at the 10 kV, 35 kV, and 110 kV levels. When an upstream constraint is violated, an improved Entropy-weight TOPSIS (EW-TOPSIS) model reallocates the available capacity according to both network constraints and zone priority. The case study indicates that the method can identify upstream bottlenecks that are hidden in local assessments, preserve residential charging demand, and provide zone-specific guidance for EVCS expansion. Full article

Evaluating the efficiency of hydraulic turbines in existing hydroelectric power plants is often challenging due to the absence of complete manufacturer curves, a lack of reliable historical data, or nonexistent formal efficiency testing. This is especially common among units that have been operating for many years. While technical standards define rigorous procedures for determining efficiency under controlled conditions, there is still a lack of systematic approaches suited to data-constrained environments. This study proposes an empirical methodology for estimating the efficiency of hydraulic turbines in service. The approach is based on defining a reference efficiency value related to specific speed, followed by applying successive penalties to account for partial load operations and aging effects. The formula is expressed in the dimensionless efficiency domain and adopts a multiplicative structure that explicitly incorporates the main loss mechanisms. The methodology was then applied to a case study evaluating a Small Hydroelectric Power Plant, specifically on a 26-year-old refurbished Francis unit, yielding an estimated efficiency of approximately 79%. A comparison between linear and exponential degradation models showed a difference of less than 0.1 percentage point, while energy-balance validations showed a difference of less than 3%. The results demonstrate that this method offers a physically consistent and practical tool for assessing the performance of older hydroelectric plants, particularly under limited data availability conditions. Full article

Background/Objectives: Immediate-loading interim implant-supported complete-arch fixed dental prostheses (ISCFDPs) are widely used for immediate loading in edentulous patients. Although traditional denture conversion techniques are well established, newer systems aim to improve efficiency and prosthesis integrity. This clinical report aims to describe and compare four chairside conversion techniques for immediate-loading interim ISCFDPs. Methods: Four clinical cases were treated using different conversion techniques, including conventional denture conversion, guided conversion with static computer-assisted implant surgery (s-CAIS), and two closed-mouth pickup systems (SMART Denture Conversion and EasyPro). Clinical workflows, procedural characteristics, and prosthetic considerations were evaluated. Results: All techniques enabled the successful fabrication of immediate-loaded interim ISCFDPs. Conventional conversion was flexible and cost-effective but technique-sensitive and associated with increased risk of prosthesis weakening. Guided conversion improved structural integrity and reduced intraoral adjustment but required precise planning and higher costs. Closed-mouth systems preserved occlusion, minimized denture modification, and reduced chairside time, though they relied on proprietary components and had limited clinical evidence. Conclusions: Each conversion technique presents distinct advantages and limitations. Selection should be based on clinical conditions, available resources, and clinician experience. Further studies are needed to validate the long-term outcomes of emerging conversion systems. Full article

Background: Overexpression of immune cell populations leads to self-amplifying cytokine loops, contributing to chronic inflammation in both allograft rejection and autoimmune conditions. Tacrolimus (TAC), despite being a potent immunosuppressant, has limitations; its systemic adverse effects include nephrotoxicity, neurotoxicity, and high variability in tissue exposure in patients. Currently available therapeutic options are limited by the lack of targeted and localized drug delivery systems, resulting in ineffective control over drug-release behavior. Moreover, TAC being highly lipophilic poses challenges for formulation development. To address these gaps, this study focuses on developing a thermoresponsive hydrogel platform comprising distinct nanocarriers for localized delivery of TAC. The nanocarriers include nanoemulsion (NE) and micelles as TAC carriers, and their particle sizes are specifically engineered at the nanoscale for differential release behavior and to support immune cell targeting (macrophages and T-cells). Incorporation into a thermoresponsive hydrogel matrix enables it to act as a local depot at the injection site and deliver TAC with a slow, extended-release profile. Methods: TAC was loaded into a coconut-rich lipid-phase-based NE via high-pressure microfluidization. Simultaneously, TAC-loaded micelles were optimized using a full-factorial design of experiments (DoE) and manufactured via the thin-film hydration method. Both nanocarriers were evaluated for long-term colloidal stability assessments. Hydrogels were produced maintaining aseptic conditions for sterile batch production. Rheological characterization was performed to assess sol-gel transition, thermoreversibility, and injectability, and in vitro release studies were conducted to evaluate TAC diffusion from the developed nanoformulations. Results: Developed nanocarriers resulted in distinct particle sizes in NE (80–85 nm) and micelles (15–17 nm) with successful TAC loading maintaining long-term colloidal stability. The developed TAC-loaded dual-nanocarrier hydrogel (Dual-HG) showed thermoresponsive behavior and gelation at 37 °C, forming as a local depot. In vitro release studies showed slow and extended tacrolimus release from hydrogels and demonstrated particle size-dependent release behavior between the NE and micelle. Conclusions: Therefore, our study highlights a novel dual nanocarrier hydrogel platform combining TAC-NE and TAC-micelle for localized delivery. The findings support that nanocarriers can be engineered to modulate drug diffusion behavior. Notably, the dual nanocarrier within a thermoresponsive hydrogel platform can be used to deliver one or multiple drugs locally, minimizing systemic exposure when sustained local immunosuppression is required. The 25 mL scale sterile batch production of hydrogels emphasizes their suitability for future translational applications. Full article

Silica dispersion in rubber matrices remains a critical issue due to the polarity mismatch between silica and the rubber phase. This study aimed to synthesize functionalized liquid polyisoprene rubber (F-LIR) and evaluate its role in improving the interfacial interaction between silica and solution styrene–butadiene rubber (SSBR). F-LIR was synthesized by introducing an alkoxysilane-containing functionalizing agent at the termination stage of anionic polymerization. Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy (¹H-NMR) were used to confirm the successful introduction of silyl groups at the chain ends of liquid polyisoprene. The optimal loading of F-LIR in SSBR was evaluated through bound rubber content, dynamic mechanical analysis, and mechanical performance testing. The results demonstrated that F-LIR improved the tensile strength, modulus at 300% elongation, and bound rubber content of SSBR composites. These enhancements are attributed to the reaction between the silyl groups of F-LIR and surface hydroxyl groups of silica, together with the co-crosslinking interaction between F-LIR and SSBR. The composites containing 4 phr F-LIR exhibited the best overall balance of properties. This study provides a novel method for synthesizing F-LIR, which bridges silica and the rubber matrix by enhanced filler–rubber interactions at the filler–rubber interface. Full article

Masonry retaining walls are widely used in mountainous regions but are susceptible to progressive internal damage under environmental and operational loads, which is often difficult to detect through conventional visual inspection. To address this problem, this study proposes a baseline-free vibration-based damage identification method for existing masonry retaining walls. The method combines impulse response function (IRF) estimation with wavelet packet decomposition (WPD) and introduces a scalar damage index, termed the energy ratio standard deviation (ERSD). Unlike conventional WPD energy ratio deviation (ERD) vectors, ERSD condenses multi-band energy redistribution into a single positive scalar for each sensor location, thereby facilitating spatial interpolation and field-level damage localization without modal extraction. The method was validated through four monthly impact hammer tests on a masonry retaining wall in Zhenjiang, China. The results show that non-zero ERD vectors indicate vibration energy redistribution between successive monitoring states, while the spatial peak of ERSD identifies the most likely damage zone. The ERSD maximum occurred at point 5 and was confirmed by post-test visual inspection, which revealed a local crack of approximately 0.8–1.2 mm in the adjacent mortar joint. To avoid overfitting with the limited four-test dataset, the temporal trend of ERSD was evaluated using a linear regression and finite-difference progression rates rather than a high-order polynomial. The proposed method provides a practical preliminary screening tool for field damage localization; however, its quantitative damage severity calibration requires further validation using controlled stiffness-reduction tests and environmental compensation models. Full article

The long-term success of implant-supported prostheses (ISPs) is strongly influenced by material selection, which affects stress distribution within the implant system and surrounding cortical bone. This study aimed to assess the biomechanical behavior of a four-unit ISP supported by two implants in the posterior region, using different framework and superstructure material combinations through dynamic finite element analysis (FEA). Methods: A three-dimensional (3D) edentulous mandibular model was created using Mimics software, with two implants placed in the first premolar and second molar regions. Four framework materials—titanium (Ti), glass fiber–reinforced composite (GFRC), 3Y-TZP zirconia, and polyether ether ketone (PEEK)—were combined with two superstructure materials, 5Y-TZP zirconia and resin-matrix ceramic (RMC), forming eight groups. Dynamic loading simulated chewing forces, and stress distribution was analyzed using the von Mises criterion. Results: The results demonstrated that 3Y-TZP zirconia frameworks generated the highest stress values across implants, abutments, and cortical bone. RMC crowns consistently produced lower stress than 5Y-TZP zirconia across all the groups. PEEK showed the highest displacement, followed by GFRC, zirconia, and Ti. Conclusion: Materials with higher Young’s modulus tended to exhibit greater stress transfer to the implant, implant components, and cortical bone. In contrast, polymer-based materials may show a tendency toward greater deformation and displacement compared with metallic and ceramic materials. Full article

Evaluating intrusion detection methods at the level of individual MITRE Adversarial Tactics, Techniques, and Common Knowledge (ATT&CK) for Industrial Control System techniques requires Operational Technology traffic in which each attack sequence carries its MITRE technique identifier as ground truth. Publicly available Industrial Control System datasets either provide coarse attack-versus-benign labels (SWaT, WADI, CIC-APT-IIoT) or require ex-post technique reconstruction from CALDERA operation logs, and therefore do not support per-technique benchmarking. We describe one primary contribution and two supporting contributions, demonstrated on one Modbus/Raspberry-Pi programmable logic controller/CALDERA/convolutional bidirectional Long Short-Term Memory autoencoder (CNN-BiLSTM-AE) use case. The primary contribution is an in-orchestrator labelling methodology for per-technique-labelled Industrial Control System attack capture. Its single load-bearing property is that the campaign orchestrator owns the label primitive and writes each per-sequence technique identifier into the capture artefact at injection time, eliminating ex-post log-to-packet alignment. The first supporting contribution is a protocol-aware detection pipeline. Its load-bearing architectural choice is a priority-ordered protocol router that dispatches each labelled flow to a per-protocol detector plug-in (protocol-aware features here, with generic-flow features admissible as an alternative plug-in policy on the same router). The second supporting contribution is a suite of four reproducible CALDERA chains (three Information-Technology-to-Operational-Technology kill chains plus one enterprise-side control) that exercise the labelling methodology end-to-end and the detection pipeline along complementary detection paths. All three contributions are platform-independent: any ATT&CK-aligned emulator and any fieldbus protocol can host the labelling methodology, and any detector trained on an admissible feature space can plug into the router. The dataset contains 40,000 benign and 9997 attack Modbus sequences spanning four ATT&CK techniques (T0802 Automated Collection, T0831 Manipulation of Control, T0836 Modify Parameter, T0846 Remote System Discovery). On this dataset, the CNN-BiLSTM-AE reaches a 100% true-positive rate (TPR) at the 98th-percentile benign threshold across all four techniques and a 99.7% overall TPR at the tighter 99.5th-percentile threshold, with per-technique TPR between 96.1% (T0836 Modify Parameter) and 100% (T0802 Automated Collection, T0846 Remote System Discovery). Across the four CALDERA chains, the Modbus autoencoder produces 234 protocol-layer detections and the Security Information and Event Management (SIEM) rule set produces 30 alerts, with per-chain tactic coverage between 0.714 and 0.786 and CALDERA-ability success rates between 0.800 and 0.857. Full article

Background/Objectives: Superparamagnetic iron-oxide nanoparticles (SPIONs) bearing poly(methacrylate) brushes were synthesized via surface-initiated atom-transfer radical polymerization (SI-ATRP) as magnetically responsive nanoplatforms. Three brush architectures, poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(poly(ethylene glycol) methacrylate) with six ethylene-oxide units (PPEGMA6) and ten units (PPEGMA10), were grown from a dopamine-anchored initiator and covalently loaded with methotrexate (MTX). Methods: Physicochemical characterization confirmed successful polymer grafting, tunable hydrodynamic size (185–1320 nm before MTX conjugation and 427–694 nm after), retained superparamagnetic properties (22–69 emu g⁻¹), and high drug payloads, with PPEGMA6 achieving 131 µg mg⁻¹. MTX conjugation induced partial compaction of the polymer shell yet maintained ζ-potentials conducive to colloidal stability. Results: In vitro assays showed negligible toxicity toward primary human fibroblasts, whereas MTX-decorated formulations induced a pronounced concentration-dependent cytotoxic effect in MCF-7 breast cancer cells, reaching 69% loss of viability—significantly higher than free MTX. Structure–activity analysis attributes the superior performance of PPEGMA6-MTX to its balanced brush density, high payload, and favorable surface charge. Conclusions: These findings demonstrate that precise modulation of polymer brush architecture via SI-ATRP yields SPION-based nanocarriers that integrate MRI visibility and the potential for magnetic guidance and targeted chemotherapy. The PPEGMA6-MTX construct is highlighted as a promising platform for future preclinical investigations. Full article

Exhaust Gas Temperature (EGT) is a critical parameter in Gas Turbines (GTs) in terms of performance monitoring, fault detection, and operational optimization. In this study, a comprehensive and data-driven modeling approach was developed to predict EGT under variable load conditions and different Inlet Guide Vane (IGV) positions in a 401 MW GT unit located in a Combined Cycle Power Plant (CCPP) with a single-shaft design. A large-scale dataset obtained from a total of 18,334 h of real operating conditions was used in the study. Operational parameters such as Gas Turbine Power Output (GTPO), IGV, Compressor Inlet Temperature (CIT), Fuel Gas Flow (FGF), and Lower Heating Value (LHV), together with environmental parameters such as Atmospheric Pressure (AP) and Relative Humidity (RH), were evaluated simultaneously, and the combined effect of these variables on EGT was investigated. In order to model the nonlinear relationships between EGT and the input variables, six different tree-based ensemble learning methods, namely Bagged Trees, Random Forest, Gradient Boosting, eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Categorical Boosting (CatBoost), were applied and compared. The results showed that all models were able to predict EGT with high accuracy. The most successful model was LightGBM, which achieved the best overall prediction performance with a Coefficient of Determination (R²) of 0.9703 and a Root Mean Square Error (RMSE) of 1.5280. The analyses revealed that the most influential parameters affecting EGT were GTPO, CIT, FGF, and IGV, whereas the environmental variables had secondary but still significant effects. The proposed approach provides a reliable and computationally efficient tool for sensor validation, fault detection, and predictive maintenance applications. Full article

Objectives: Curcumin possesses well-documented anticancer activity; however, its clinical translation is hindered by poor aqueous solubility and limited bioavailability. The present study aimed to engineer pH-dependent bovine serum albumin (BSA)–based nanocarriers for curcumin delivery and to evaluate their physicochemical characteristics, controlled release behavior under gastrointestinal pH conditions, and in vitro anticancer efficacy against the human colon cancer cell line Colo-205. Methods: Curcumin-loaded bovine serum albumin nanoparticles (Cu-BSA-NPs) were fabricated using a desolvation technique followed by chemical crosslinking. Particle size, zeta potential, and polydispersity index (PDI) were assessed by dynamic light scattering. Morphology was examined using scanning electron microscopy (SEM), while structural and thermal properties were evaluated by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Drug loading capacity and entrapment efficiency were quantified spectrophotometrically. In vitro drug release was investigated using a gastrointestinal pH-transition model (pH 1.2, 6.8, and 7.4). Cytotoxic activity was assessed using the sulforhodamine B (SRB) assay on Colo-205 cells. Results: The engineered Cu-BSA-NPs exhibited particle sizes ranging from 96.7 ± 10.5 to 126.4 ± 35.8 nm, with PDI values between 0.289 and 0.581 and zeta potentials from −18.2 ± 1.01 to −34 ± 1.0 mV, indicating nanoscale dimensions and moderate colloidal stability. SEM analysis revealed spherical nanoparticles with smooth surfaces and uniform morphology. Entrapment efficiency ranged from 6.59 ± 1.11% to 52.98 ± 0.65%, while drug loading efficiency varied between 1.308 ± 0.206% and 16.744 ± 0.266%. In vitro release studies demonstrated minimal drug release under acidic (pH 1.2) and near-neutral (pH 6.8) conditions, followed by significantly enhanced release at pH 7.4, confirming pH-dependent behavior of the albumin matrix. Cytotoxicity studies showed significant antiproliferative activity against Colo-205 human colon cancer cells. Conclusions: The findings demonstrate successful engineering of albumin-based nanocarriers capable of modulating curcumin release under physiologically relevant pH conditions and enhancing in vitro anticancer activity. Although limited to in vitro evaluation, this study highlights the potential of protein-based nanoplatforms as adaptable delivery systems for colon cancer therapy. Further in vivo investigations are warranted to validate their translational and therapeutic potential. Full article