Search Results (33,512)

This paper presents the results of research conducted as part of a bilateral cooperation project between National Research Council (Italy) and Chinese Academy of Cultural Heritage (China) for the conservation of the earthen walls of Ancient Ulanbay City (Xinjiang, China). In 2007 and 2012, conservation interventions were carried out on the remains of the ancient walls, focusing on areas at risk of collapse. This involved the construction of new adobe masonry (sun-dried earthen bricks and mud mortar) to support the ancient rammed-earth walls, which required consolidation treatments due to their exposure to weathering. In order to support the site’s conservation efforts, several nanoproducts were selected for testing as consolidants for the adobe bricks. Nano-silica (NanoEstel) and nano-lime (Calosil E25), with and without ethyl silicate, and a nano-calcium oxalate-functionalized ethyl silicate (SurfaPore FX WB) were tested and compared with commonly used products for surface consolidation. Ethyl silicate was applied alone as a reference treatment. The mixtures tested in this research had not been previously explored, thus offering new opportunities to identify suitable solutions for the consolidation of earthen structures exposed to environmental conditions. In this study, adobe bricks were sampled from the archaeological site, and the effectiveness of each treatment was assessed based on changes in chromatic appearance, cohesion, and water behaviour. The results showed different behaviours of nanoproducts. Nano-silica, alone or especially in combination with ethyl silicate, is overall more effective than nano-lime for the consolidation of earthen materials, thanks to its greater compatibility with these materials. Full article

The food packaging industry requires sustainable solutions to reduce plastic waste and replace synthetic additives. This study addresses the need for scalable methods to transform conventional polyethylene terephthalate (PET) packaging into active food preservation systems using natural biocides. Commercial PET packaging was surface-activated using industrial-scale corona treatment, followed by coating with natural biocides—carvacrol (CV) and trans-cinnamaldehyde (tCN). The resulting active packaging materials (PET-CV and PET-tCN) were characterized using XRD, FTIR, SEM, AFM, and desorption kinetics. Packaging properties including mechanical strength, oxygen barrier, antioxidant (DPPH), and antibacterial activity (against S. aureus and E. coli) were evaluated. Real-food preservation tests were conducted using fresh minced pork (4 °C, 6 days) and table olives (23 °C, 21 days), monitoring microbiological (TVC), colorimetric (CIE L*a*b*), and pH changes. Corona treatment successfully anchored both biocides through physical adsorption, with tCN exhibiting stronger surface interaction (desorption energy: 128.0 kJ/mol). Both coatings significantly improved oxygen barrier properties (61% reduction for PET-CV, 80% for PET-tCN). PET-tCN demonstrated superior antibacterial activity (inhibition zones: 15.0 mm against E. coli). In pork preservation, PET-tCN achieved a 2-log reduction in TVC, maintained meat redness (a*: 12.80 vs. 5.10 for control), and stabilized pH. For olives, PET-tCN reduced TVC by 2.35 log cycles and preserved green color. This corona-assisted coating approach, demonstrated here at laboratory scale, successfully transforms inert PET into multi-functional active packaging with potent antimicrobial, antioxidant, and barrier properties, significantly extending food shelf-life and offering a sustainable solution for reducing food waste. Full article

Background/Objectives: Spotty liver disease (SLD), caused by Campylobacter hepaticus, is an emerging disease that leads to substantial production losses in the egg industry. The shift toward antibiotic-free and cage-free production systems has further intensified the impact of SLD. The current control measures largely rely on autogenous killed vaccines; however, their use is constrained by the slow and fastidious growth of C. hepaticus and inconsistent efficacy. To overcome these limitations, this study aimed to identify immunogenic mimotopes as vaccine candidates and express them on the surface of an avian pathogenic Escherichia coli (APEC) vector. Methods: To identify immunogenic mimotopes, Ph.D.-12 phage display peptide library was screened using the hyperimmune serum raised against killed whole-cell C. hepaticus in specific pathogen-free chickens. Subsequently, the outer membrane protein C (OmpC) of E. coli was used as a scaffold for constructing a surface display library. A single restriction site, PstI, located in the seventh external loop of OmpC, was strategically utilized to insert each 12-amino-acid mimotope with a six-histidine (6xHis) tag sequence at its N-terminus, generating ompC + mimotope fusion constructs. These constructs were cloned into the inducible expression vector pTrc and electroporated into an E. coli DH5α ∆ompC strain, which lacked ompC. The surface expression of the mimotopes was confirmed in vitro. The verified ompC + mimotope constructs were subsequently subcloned into the pYA3422 constitutive expression vector and electroporated into the APEC PSUO78 ∆aroA ∆asd vaccine vector strain. A chicken vaccination–challenge trial was conducted using nine groups of chickens, including an unvaccinated challenged control and an unvaccinated–unchallenged negative control. Each experimental group received a mixture of two recombinant E. coli strains carrying different mimotopes at a dose of 1 × 10⁹ CFU, which were administered orally twice at 16 and 18 weeks of age. Results: Fourteen immunogenic mimotopes corresponding to 13 different C. hepaticus proteins were identified as potential vaccine candidates. The expression of these mimotopes on the surface of the E. coli was successfully demonstrated using the OmpC-mediated surface display system. Of the 14 mimotopes tested, two flagellar-related peptides and one major outer membrane protein (MOMP)-derived peptide elicited significant immune responses and conferred protection against the C. hepaticus challenge. Conclusions: We successfully developed a functional E. coli surface display system that was capable of expressing 12-amino-acid mimotopes of C. hepaticus, providing a robust platform for evaluating vaccine candidates against SLD. Immunogenicity and efficacy studies in chickens demonstrated that three identified mimotopes conferred protection against C. hepaticus colonization of the bile and liver. Future in vivo investigations are necessary to develop and evaluate the immunogenicity and protective efficacy of a multivalent mimotope vaccine consisting of three identified mimotopes against both C. hepaticus and APEC, utilizing the ΔaroA Δasd APEC PSU078 strain as the vaccine vector. Full article

This study evaluated eleven resin cements used as core build-up materials by examining the following properties: (a) push-out force between root dentin and the fiber post; (b) pull-out force between the fiber post and the core build-up material; (c) shear bond strength of the resin cement to root dentin; (d) flexural strength of the resin cement; and (e) flexural modulus of elasticity of the resin cement. The purpose of this investigation was to clarify the relationships between recently available universal adhesives, core build-up materials, resin cements, and fiber posts. All experiments were performed at two evaluation periods: after 1 day of water storage (Base) and after 20,000 thermocycles (TC 20k). For the push-out test, simulated post spaces were prepared in single-rooted human premolars. The specimens were sectioned perpendicular to the long axis into 2 mm-thick slices and then subjected to push-out testing to assess the bond strength of the dentin–resin cement–fiber post complex. No significant differences in bonding performance were found between Base and TC 20k. These findings suggest that universal adhesives used for pretreatment of multiple substrates in fiber post cementation can provide not only strong but also durable adhesion over time. Full article

The 2025 approval of the selective NaV1.8 blocker suzetrigine for acute pain marked a pivotal advance in analgesic drug development. Yet the subsequent failure of Vertex’s next-generation NaV1.8 inhibitor VX993 to demonstrate clinical analgesia underscores enduring challenges in translating mechanistic promise into patient benefit. This review examines why promising targets and compounds, spanning NaV and TRP channels, often falter and outlines a path toward more reliable target selection and validation. I first summarize the pain pathway, from nociceptor transduction through spinal processing to cortical perception, emphasizing how inflammation and peripheral sensitization reshape excitability. Historically serendipitous, pain drug discovery now prioritizes molecular precision. Most approved chronic pain therapies act in the CNS and are limited by modest efficacy and adverse effects. Nociceptor-enriched targets (NaV1.7/1.8/1.9; TRP channels) remain attractive, yet redundancy among NaV subtypes and the necessity of blocking targets at the correct anatomical sites complicate translation. Human genetics and multi-omics provide a powerful, unbiased engine for target discovery. Rare high-impact variants offer strong causal hypotheses, while common polygenic contributions illuminate broader susceptibility. Large biobanks increasingly reveal a mismatch between legacy pain targets and genetically supported candidates across neuronal and non-neuronal cells. Human DRG transcriptomics highlight NaV channel redundancy. Human in vitro electrophysiology and PK/PD analyses show suzetrigine achieves ~90–95% NaV1.8 engagement, yet neurons can still fire unless additional channels are blocked. Species differences and drug distribution (including BBB/PNS penetration and P-gp efflux) critically influence efficacy; centrally accessible blockade (e.g., for NaV1.7 or TRPA1) may be necessary to achieve robust analgesia, challenging peripherally restricted strategies. Osteoarthritis illustrates how obesity-driven metabolic inflammation, synovial immune activation, subchondral bone remodeling, and specific nociceptor subtypes converge to drive mechanical pain. Multi-omic integration across diseased human tissues can pinpoint causal processes and cell types, enabling more selective and safer target choices. I propose a practical framework for target validation that integrates: (i) rigorous human genetic support; (ii) cell-type and site-of-action mapping; (iii) human-relevant electrophysiology and PK/PD with verified target engagement; (iv) species-appropriate models; (v) consideration of modality (small molecule, biologic, RNA, targeted protein degradation). Advancing genetically and anatomically aligned targets, tested at the right sites and exposures, offers the best path to genuinely effective, better-tolerated pain therapeutics. Full article

This work presents the development of a wrist-worn wireless sensor system for high-accuracy indoor human zone tracking. The proposed system employs machine learning techniques to combine data from multiple sources, including a Received Signal Strength Indicator (RSSI) from wireless signals, three-axis acceleration, and three-axis angular velocity. A prototype wearable wireless sensor device was implemented using a SparkFun Thing Plus-XBee3 microcontroller supporting the Zigbee/IEEE 802.15.4 standard at 2.4 GHz, integrated with a six-degree-of-freedom IMU sensor (MPU-6050). Experiments using one wrist-worn sensor as a transmitter and one base station as a receiver were conducted in a two-story residential building environment covering three zones (i.e., staircase area, living room, and dining room) under static and dynamic test scenarios. Classification performances of 33 machine learning classifiers with different data feature groups and window sizes were evaluated. The results demonstrate the achievement of wrist-worn wireless sensor system development. The system exhibits high communication reliability with a packet delivery ratio (PDR) of 99.99% and can efficiently track data signals in real time. Results indicate that using only raw RSSI data achieves 75.0% accuracy in classifying human zones. However, when statistical RSSI features and accelerometer data fusion are applied, accuracies significantly increase to 98.7% (static scenario, wide neural network with a window size of 25) and 99.6% (dynamic scenario, Fine k-NN). These results demonstrate the system’s potential for indoor human tracking applications. Full article

Effective online bond wire degradation assessment of power modules is crucial for ensuring long-term stability. However, its electrical aging indicators are often influenced by junction temperature ($T_j$), and conventional $T_j$ monitoring methods are also affected by the aging process itself, creating a contradiction. This paper proposes a thermal–electrical co-modeling method designed to reduce reliance on accurate $T_j$. A major challenge of the method is the traditional thermal network models, which rely on case temperature ($T_c$). These models are affected by thermal coupling and have a slow dynamic response, making them difficult to integrate with electrical models. To overcome this, a $T_j$ monitoring method based on in situ sensor fabrication is employed to shorten thermal conduction path and simplify thermal network. This method results in a much faster dynamic process and is unaffected by thermal coupling, as confirmed through both theoretical analysis and finite element simulation. To validate the proposed method, bond wire degradation assessment is conducted using the on-state voltage drop ($V_{ce}$). Tested in practical circuits, this design successfully enables online evaluation of bond wire degradation, which is unaffected by $T_j$. Full article

Background: Chronic low-grade inflammation plays a central role in the pathogenesis of type 2 diabetes (T2DM) and its complications. Neopterin, a marker of macrophage activation and Th1-mediated immune response, has been associated with cardiovascular disease and metabolic disorders. However, its relationship with diabetic autonomic neuropathy remains insufficiently investigated. Methods: We conducted a cross-sectional study including 129 participants (93 with T2DM and 36 with obesity without carbohydrate disturbances). Clinical, anthropometric, and biochemical assessments were performed. Cardiovascular autonomic neuropathy was evaluated using Ewing cardiovascular reflex tests and sudomotor dysfunction scoring. Neopterin concentrations were measured in serum. Correlation, ROC, and logistic regression analyses were performed. Results: Neopterin levels were not significantly different between T2DM and obesity groups. No differences were observed in patients with versus without peripheral neuropathy, nephropathy, or retinopathy. However, neopterin levels were significantly higher in individuals with cardiovascular autonomic neuropathy (p = 0.013). Neopterin correlated with cardiovascular autonomic neuropathy score, sudomotor dysfunction, fasting glucose, fasting insulin, and HOMA-IR. It showed a moderate negative monotonic correlation with eGFR (Spearman’s rho = −0.41, p< 0.001). In multivariable logistic regression adjusted for age, HbA1c, BMI, eGFR, and diabetes duration, each 1-SD increase in neopterin was associated with 2.67-fold higher odds of cardiovascular autonomic neuropathy (95% CI 1.21–5.89; p = 0.015). Conclusions: Circulating neopterin is independently associated with cardiovascular autonomic neuropathy in T2DM but not with classical microvascular complications. These findings suggest a potential role of immune-mediated mechanisms in the pathogenesis of diabetic cardiovascular autonomic neuropathy. Full article

This paper focuses on the critical issue of change point detection in panel linear regression models and proposes a novel jump information criterion (JIC) for efficient solution. The core innovation of this criterion lies in reconstructing the traditional change point hypothesis testing problem into a parameter estimation problem: under the null hypothesis ($H_0$, i.e., no change point exists in the model) and the alternative hypothesis ($H_1$, i.e., a change point exists in the model), the number of potential change points is set to 0 and 1 for modeling and solution, respectively. To verify the theoretical reliability of the proposed method, this paper systematically establishes the consistency of the change point count estimator through rigorous mathematical deductions and further derives its optimal convergence rate. In terms of numerical validation, extensive Monte Carlo simulation experiments and real data empirical analysis both demonstrate that the estimator constructed based on JIC exhibits excellent performance in change point identification accuracy, stability, and computational efficiency, providing a reliable new tool for structural break analysis in panel data models. Full article

This paper investigates how the thickness of dogbone tensile specimens made from heat-treated Hastelloy-X alloy produced by Laser Powder Bed Fusion (LPBF) influences their mechanical properties and microstructure. The focus of the investigation is on surfaces in an “as-built” condition and considers a range of thickness from 3 to 1 mm. The “as-built” surfaces condition is a fundamental outcome, considering that LPBF technology’s key feature is the ability to produce intricate and complex geometries that are difficult to achieve with conventional manufacturing technologies. The specimens were fabricated according to ASTM E8/E8M-21 and were heat-treated in a vacuum furnace at 1150 °C for two hours. The microstructure of the material was evaluated through porosity, EBSD, and Microhardness analyses. The mechanical properties were evaluated through tensile tests conducted at room temperature on dogbone specimens fabricated both parallel and perpendicular to the building direction. The findings indicate a significant reduction in mechanical properties that could be correlated with the reduction in specimen thickness, reflecting a gradual decline from the baseline. Specifically, a 14% decrease in Ultimate Tensile Strength (from 612 to 528 MPa), an approximately 19% reduction in Young’s Modulus (from 190 GPa to 153 GPa), and a 32% decrease in Elongation at Break (from 59.2% to 40.0%) were observed. Furthermore, it was noted that the printing orientation of the specimens significantly affects their mechanical properties, regardless of thickness. Overall, the results suggest that applying standard heat treatment under specific conditions, such as with a thin, exposed wall of about 1mm with a striped strategy, may not lead to adequate material performance. Full article

The study focused on the development and optimization of plastic deformation of pure M1E copper using an unconventional hydrostatic extrusion (HE) process aimed at improving the performance of electrodes used in electrical discharge machining (EDM). The process was designed to refine the microstructure while maintaining the high electrical conductivity required for EDM applications. Optimization of a three-stage HE process (cumulative strain ε = 2.51) resulted in the formation of an ultrafine-grained structure (d₂ ≈ 370 nm), leading to a significant increase in mechanical strength (UTS ≈ 400 MPa) while preserving very high electrical conductivity (~99% IACS). This combination of properties is particularly important for EDM electrodes, as it allows improved wear resistance without compromising electrical performance. Due to the application-oriented nature of the study, the HE-processed copper was tested under industrial EDM conditions. Wear tests were conducted using seven electrodes of different geometries required for the production of a sample injection mold. The results demonstrated a substantial reduction in electroerosion wear of HE-processed electrodes (30–90%) compared with undeformed copper, together with up to 25% improvement in surface quality. These findings indicate that hydrostatic extrusion is an effective method for producing high performance EDM electrode materials with improved durability and machining quality. Full article

This study explores the structural safety, mechanical response and optimal construction parameters of the Horizontal Directional Drilling (HDD) technology applied in airport rigid pavements novelly for navigation lighting renovation. This study adopts a combined research method of three-dimensional finite element modeling (FEM) and field tests (full-scale 4C and 4E class airport runway sections). The reliability of the model is verified by the measured data using a Heavy Weight Deflectometer (HWD). The effects of drilling depth, drilling position and typical aircraft loads on the stress and deformation at the bottom of the pavement slab are systematically analyzed. Then, drilling, grouting and non-destructive testing are carried out in the field full-scale test section to investigate the change in pavement bearing capacities. The results show that minimized influence on the mechanical properties of the pavement can be achieved by using 15 cm drilling depths at either slab center or joints. The pavement stiffness slightly decreases by a maximum of 18.9% after drilling. According to the field grouting test, the Impulse Stiffness Modulus (ISM) of most measuring points can be recovered to the original level before drilling. The use of a 10 cm diameter HDD driller meets the structural safety requirements of airport pavements. The HDD technology induces minimized pavement damage and influence on the bearing capacity of the airport runway structure compared with traditional construction technologies, highlighting its advantages in airfield navigation lighting renovations. Full article

Background and Objectives: Burn wounds are associated with delayed healing, infection, and pathological scarring. Effective repair requires tightly regulated immune and oxidative stress responses, including macrophage polarization. This study evaluated the association of the photosensitizer Rose Bengal, delivered in a hydrogel vehicle, with macrophage polarization and oxidative stress after burn injury. Materials and Methods: Three female red Duroc pigs underwent full-thickness contact burns followed by excision and autografting. Wounds received 20% Pluronic F-127 hydrogel containing 0.1% Rose Bengal sodium, hydrogel alone, or PBS (phosphate-buffered saline) on days 1, 7, and 14 post-burn. Biopsies from days 7 and 120 were analyzed by immunohistochemistry for pan-macrophage marker, CD206 (M2 macrophages), CD3E (T-cell infiltration), and 4-hydroxynonenal (4-HNE; oxidative stress marker). Mean fluorescence intensity was analyzed using two-way ANOVA with Tukey’s post hoc test (mean ± SD, p < 0.05). Results: At day 120, Rose Bengal treatment showed higher pan-macrophage expression (0.80 ± 0.07) compared with PBS (0.62 ± 0.10; p = 0.0034), whereas the difference versus hydrogel (0.68 ± 0.07; p = 0.0628) was not significant. CD206 expression was similarly higher in Rose Bengal-treated wounds (0.77 ± 0.06) compared with PBS (0.62 ± 0.05; p = 0.0277); hydrogel also differed from PBS (p = 0.0287), without a difference between hydrogel and Rose Bengal. For CD3E, a significant main effect of treatment was observed (F(2,12) = 8.346, p = 0.0054), with lower values in Rose Bengal versus PBS at day 120 (p = 0.0360). No differences in 4-HNE were detected. Conclusions: Rose Bengal–hydrogel treatment was associated with increased macrophage presence and enhanced M2 polarization without increased T-cell infiltration. Effects were significant versus PBS but not hydrogel, suggesting Rose Bengal may contribute to a pro-regenerative immune microenvironment without excessive adaptive activation. Full article

The upscaling of turbines in the offshore wind industry has been unprecedented, as compared to 5–6 MW rated turbines 10 years ago. A typical 20–26 MW rated turbine in modern commercial applications (MingYang MySE 18.X-20 MW installed in 2025 and 26 MW prototype by Dongfang Electric tested in 2025) has been demonstrated. This scaling has been made possible by increasing rotor diameters (>250 m) and hub heights (>150–180 m) to achieve capacity factors of up to 55–65%, annual energy generation of more than 80 GWh/turbine, and significant decreases in levelised cost of energy (LCOE) to current values of up to 63–65 USD 2023/MWh globally averaged in 2023 (with minor variability in 2024 due to market changes and new regional areas). The paper analyses turbine upscaling over three levels of hierarchy, including turbine scale—rated capacity and physical aspect, project scale—multi-gigawatts of farms, and market scale—the global pipeline > 1500 GW level, and combines techno-economic evaluation, structural evaluation of loads, and infrastructure needs assessment. The upscaling has the advantage of reducing the number of turbines dramatically (e.g., 500 to 67 turbines in a 1 GW farm, as turbine size is increased to 15 MW) and balancing-of-plant (BoP) CAPEX (turbine-to-turbine foundations and cables) by some 20 to 30 percent per unit of capacity, and serial production learning rates of between 15 and 18% per doubling of capacity. But the problems that come with the increase in ultra-large designs are nonlinear increments in mass and load (i.e., blade-root and tower-bending moments), logistical constraints (blades > 120 m, nacelle up to 800–1000 tonnes demanding special vessels and ports), supply-chain issues (rare-earth materials, vessel shortages increase day rates by 30–50%), and technology limitations (aeroelastic compounded by numerical differences between reference 5 MW, 10 MW, and 15 MW models), it becomes evident that there is a significant increase in deflections of the tower and blades and platform surge/pitch responses with continued increases in power levels, but without a correspondingly mature infrastructure. The regional differences (mature ports of Europe vs. U.S. Jones Act restrictions vs. scale-up of vessels/manufacturing in China) lead to the necessity of optimisation depending on the context. The analysis concludes that, to the extent of mature markets with adapted logistics, continuous upscaling is an effective business strategy and can result in 5 to 12 percent further reductions in LCOE, but beyond that point, gains become marginal or even negative, as risks and costs increase. The competitiveness of the future depends on multi-scale/multi-market-based approaches—modular-based families of turbines, programmatic standardisation, vibration control innovations, and industry coordination towards supply-chain alignment and standards. Its major strength is that it transcends mere size–cost relationships and shows how nonlinear structural processes, aero-hydro-servo-elastic interactions, and bottlenecks in logistical systems are becoming more determinant of the efficiency of ultra-large turbines. The study demonstrates that upscaling turbines has LCOE benefits through the support of associated improvements in installation facility, supply-chain preparedness, and structural vibration control potential, based on the comparisons of quantitative loads, techno-economic scaling trends, and regional market differentiation. Full article

Ebola virus disease remains one of the most serious viral infections with no approved small-molecule treatments. The Ebola virus glycoprotein (EBOV-GP), which enables the virus’s entry to host cells, is a promising target for drug discovery. In this study, a multistage computer-aided drug discovery approach was used to identify new specific EBOV-GP inhibitors. A reliable QSAR model was built using 55 terpenoid derivatives. This model was able to predict the activity of newly designed compounds with good accuracy and validated statistical metrics ($R_{tr}^2$= 0.70; $R_{ext}^2$ = 0.73). It was subsequently applied to screen over 15,500 newly generated compounds from three lead molecules by fragment-based design tools. Predicted activity, binding affinity toward EBOV-GP, and good ADMET drug-like properties prioritized the eleven most promising hits. Through 150 ns molecular dynamics simulations, these compounds remained stable in the EBOV-GP binding site. Further binding free energy analysis (MM/PBSA) showed strong binding affinities, especially for the compounds L-60, L-832, M-1618, and L-1366. This study showed how combining QSAR, fragment-based design, docking, ADMET, and molecular dynamics could help in identifying potent and safe small molecules against the EBOV-GP. The top compounds are ready for further experimental and in vitro biological testing. Full article