Search Results (5,181)

Background/Objectives: New vaccine platforms that rapidly yield low-cost, easily manufactured vaccines are highly desired, yet current approaches lack key features. We developed the Killed Whole-Cell/Genome-Reduced Bacteria (KWC/GRB) platform, which uses a genome-reduced Gram-negative chassis to enhance antigen exposure and modularity via an autotransporter (AT) system. Integrated within a Design–Build–Test–Learn (DBTL) framework, KWC/GRB enables rapid iteration of engineered antigens and immunomodulatory elements. Here, we applied this platform to the HIV-1 fusion peptide (FP) and tested multiple antigen engineering strategies to enhance its immunogenicity. Methods: For a new vaccine, we synthesized DNA encoding the antigen together with selected immunomodulators and cloned the constructs into a plasmid. The plasmids were transformed into genome-reduced bacteria (GRB), which were grown, induced for antigen expression, and then inactivated to produce the vaccines. We tested multiple strategies to enhance antigen immunogenicity, including multimeric HIV-1 fusion peptide (FP) designs separated by different linkers and constructs incorporating immunomodulators such as TLR agonists, mucosal-immunity-promoting peptides, and a non-cognate T-cell agonist. Vaccines were selected based on structure prediction and confirmed surface expression by flow cytometry. Mice were vaccinated, and anti-FP antibody responses were measured by ELISA. Results: ELISA responses increased nearly one order of magnitude across design rounds, with the top-performing construct showing an ~8-fold improvement over the initial 1mer vaccine. Multimeric antigens separated by an α-helical linker were the most immunogenic. The non-cognate T-cell agonist increased responses context-dependently. Flow cytometry showed that increased anti-FP-mAb binding to GRB was associated with greater induction of antibody responses. Although anti-FP immune responses were greatly increased, the sera did not neutralize HIV. Conclusions: Although none of the constructs elicited detectable neutralizing activity, the combination of uniformly low AlphaFold pLDDT scores and the functional data suggests that the FP region may not adopt a stable native-like structure in this display context. Importantly, the results demonstrate that the KWC/GRB platform can generate highly immunogenic vaccines, and when applied to antigens with well-defined native tertiary structures, the approach should enable rapidly produced, high-response, very low-cost vaccines. Full article

A molecularly imprinted electrochemical sensor was developed for the selective and sensitive detection of glyphosate in Traditional Chinese Medicine samples. An excellent conductive hierarchical porous carbon substrate made from sodium alginate and ammonium chloride co-carbonization was used to build the sensor. The molecularly imprinted polymer layer was systematically designed using Density Functional Theory calculations, which identified nicotinamide as the optimal functional monomer. A deep eutectic solvent was utilized as an effective green eluent for template removal. Under optimized conditions, the sensor demonstrated a wide linear detection range from 1.0 × 10⁻⁹ to 1.0 × 10⁻⁶ M with an exceptionally low detection limit of 8.8 × 10⁻¹⁰ M. The sensor exhibited satisfactory reproducibility (RSD = 3.35%, n = 6), repeatability (RSD = 5.0% over 6 cycles), and robust stability (retaining >90% initial response after 10 days). The sensor displayed satisfactory recovery rates of 94.47–112.23% and RSD values ranging from 1.37–3.01% when applied to real traditional Chinese medicine samples, thereby confirming its accuracy and practical utility for glyphosate residue analysis in complex matrices. This study introduces an effective sensing platform that integrates rational design principles with environmentally friendly synthesis strategies for quality control in traditional medicine applications. Full article

Asymmetric friction, that is, different friction forces resisting sliding in opposing directions, works as a rectifier, transferring the applied oscillations into unidirectional motion. Locomotion of devices based on asymmetric friction is investigated by considering a model system consisting of an asymmetric friction block connected to a symmetric friction block by a spring. The symmetric friction block models the resistance to the movement by the environment. It is found that under harmonic oscillation, the system displays two distinct types of motion: Recurrent Movement (stick-slip-type movement) and Sub-Frictional Movement. The Recurrent Movement occurs when the inertia force is sufficient to overcome the frictional force. In this case, the system with asymmetric friction exhibits unidirectional locomotion, while the system with only symmetric friction oscillates about a fixed point. The Sub-Frictional Movement occurs when the inertia is insufficient to overcome the frictional force. Then the symmetric friction block moves against the asymmetric friction block and sufficiently loads the spring to enable some movement of the system. Thus, motion is generated even when the external forces are below the static friction threshold. These types of motion have been found to exhibit different types of spectral fallout: while the Recurrent Movement produces a typically observed frictional fallout 1/ω, where ω is the frequency, the Sub-Frictional Movement produces a stronger 1/ω² fallout, only observed in the development of an oblique fracture in rocks under compression. This discovery can shed light on mechanisms of rock failure in compression. Understanding of the unidirectional movement induced by asymmetric friction can be instrumental in designing novel locomotion devices that can move in narrow channels or fractures in the Earth’s crust or in extraterrestrial bodies utilising the (renewable) energy of external vibrations. Full article

Background/Objectives: The poor aqueous solubility of curcumin (CUR) limits its pharmaceutical application. Although amorphization can enhance its solubility, the amorphous form often exhibits insufficient physical stability. Co-amorphization, particularly drug–drug co-amorphous (CAM) formation, offers a promising approach to improve solubility, stability, and therapeutic efficacy. This study aimed to prepare and evaluate two CUR-based CAM systems using isoquinoline alkaloids berberine hydrochloride (BER) and palmatine hydrochloride (PAL) as co-formers to achieve simultaneous stabilization and synergistic bioactivity. Methods: CUR-BER and CUR-PAL CAM systems were prepared via rotary evaporation under vacuum at a 1:1 molar ratio. The solid-state properties were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and ¹³C solid-state nuclear magnetic resonance spectroscopy (ssNMR). Dissolution, solubility, and stability studies were conducted, while antioxidant and anticancer activities were assessed by DPPH/ABTS⁺ radical-scavenging and MTT assays using HT-29 colorectal cancer cells. Results: PXRD and DSC confirmed the formation of single-phase amorphous systems with higher glass transition temperatures, indicating strong intermolecular interactions between CUR and BER/PAL. ¹³C ssNMR spectroscopy evidenced hydrogen-bond formation between the enolic hydroxyl moiety of CUR and the methoxy oxygen atoms in BER or PAL molecules. Both CAM systems significantly enhanced the solubility and dissolution rate of CUR, with CUR-PAL CAM showing up to a 15.1-fold solubility improvement. The CAM systems also displayed superior thermal stability, photolytic stability, and improved short-term humidity resistance, together with enhanced antioxidant and anticancer activities compared with pure amorphous CUR. Conclusions: Co-amorphization of CUR with isoquinoline alkaloids effectively improved solubility, stability, antioxidant and anticancer activities, representing a promising strategy for the rational design of multifunctional amorphous CUR-based drug formulations. Full article

Among various statistical process -control (SPC) methods, control charts are widely employed as essential instruments for monitoring and improving process quality. This study focuses on a new modified exponentially weighted moving-average (New Modified EWMA) control chart that enhances detection capability under integrated and fractionally integrated time-series processes. Special attention is given to the effect of symmetry on the chart structure and performance. The proposed chart preserves a symmetric monitoring configuration, in which the two-sided design ($\mathrm{LCL}>0$) establishes control limits that are equally spaced around the center line, enabling balanced detection of both upward and downward shifts. Conversely, the one-sided version ($\mathrm{LCL}=0$) introduces a deliberate asymmetry to increase sensitivity to upward mean shifts, which is particularly useful when downward deviations are physically implausible or less critical. The efficacy of the control chart utilizing both models is assessed through Average Run Length (ARL). Herein, the explicit formula of ARL is derived and compared to the ARL obtained from the Numerical Integral Equation (NIE) in terms of both accuracy and computational time. The accuracy of the analytical ARL expression is validated by its negligible percentage difference ($\%diff$) in comparison to the results derived using the NIE approach, and the display processing time not exceeding 3 s. To confirm the highest capability, the suggested method is compared to both the classic EWMA and the modified EWMA charts using evaluation metrics such as ARL and SDRL (standard deviation run length), as well as RMI (relative mean index) and PCI (performance comparison index). Since asset values are volatile due to positive and negative market influences, symmetry is crucial in financial monitoring. Thus, symmetric control-chart structures reduce directional bias and better portray financial market activity by balancing upward and downward movements. Finally, examination of US stock prices illustrates performance, employing a symmetrical two-sided control chart for the rapid detection of changes through the new modified EWMA, in contrast to standard EWMA and modified EWMA charts. Full article

This work presents the design of a novel electrochemical sensor for highly sensitive determination of LEV, utilizing a sensing platform based on a newly synthesized, high-purity manganese (III) porphyrin complex [5,10,15,20-tetrayltetrakis(2-methoxybenzene-4,1-diyl) tetraisonicotinateporphyrinato] manganese (III) porphyrin (MnTMIPP). The successful synthesis of the MnTMIPP complex was verified using ultraviolet–visible (UV–Vis) and infrared spectroscopy (IR). The sensing electrode was fabricated by depositing the synthesized material onto an indium tin oxide (ITO) electrode via a drop-coating method. Under optimized experimental conditions, the proposed sensor demonstrated a wide dynamic range, from 10⁻⁹ M to 10⁻³ M, with a low calculated detection limit of 4.82 × 10⁻¹⁰ M. Furthermore, the MnTMIPP/ITO electrode displayed interesting metrological performance: high selectivity, reproducibility, and stability. Successful application in spiked river water and saliva samples with satisfactory recovery rates confirms the sensor’s potential as a reliable and cost-effective platform for monitoring LEV in real-world environments. Full article

This study presents a cradle-to-grave Life Cycle Assessment (LCA) and cost analysis of next-generation low-temperature district heating networks based on water-condensed electric booster heat pumps. The research, conducted within the ENEA Portici Research Center framework, evaluates multiple case studies to assess environmental and economic sustainability. The system boundaries include heat generators (geothermal heat pump, solar thermal, and photovoltaic–thermal hybrid), network configurations (tree vs. ring), supply temperatures (25 °C vs. 45 °C), and renewable electricity shares (0–100%). Environmental impacts were quantified using the Environmental Footprint 3.1 method, focusing on key indicators such as climate change, resource use, and human toxicity. The results show that supply temperature is a critical factor: 45 °C scenarios lead to notably higher impacts, while network configuration has only marginal effects. Among generation technologies, the photovoltaic–thermal system proved the most sustainable, despite higher investment costs, whereas the solar thermal system displayed the largest environmental burden but lower costs. Geothermal systems showed intermediate performance, with notable impacts from mineral resource use. Renewable electricity integration consistently improved environmental outcomes, reducing climate change impacts by up to 10%. Storage system comparison revealed lithium iron phosphate (LFP) batteries as the most advantageous solution for electrical storage, and phase-change materials (PCM), particularly Rubitherm15, as the most environmentally favorable option for thermal storage, although traditional water tanks remain more cost-effective. Overall, the study highlights the crucial role of renewable integration and temperature optimization in enhancing the eco-efficiency of low-temperature district heating networks, providing guidelines for future sustainable design and deployment. Full article

Extended reality (XR) is increasingly used to address productivity, communication, and safety challenges in the construction industry, but large-scale adoption within Construction 4.0 remains limited. The existing reviews rarely provide an integrated perspective that jointly examines XR applications, underlying technology stacks, and the barriers that constrain implementation. This study fills that gap by combining a PRISMA-compliant systematic review with a bibliometric analysis of 76 journal articles published between 2019 and 2024. The review maps XR usage in construction, which XR modes, devices, and graphics engines are most prevalent, and which barriers hinder deployment in real projects. Design visualization and coordination, immersive training, and remote assistance or inspection emerge as the dominant application areas. Augmented reality (AR) and virtual reality (VR) lead the technology landscape, with Microsoft HoloLens and Meta Quest as the most frequently reported head-mounted displays and Unity as the main graphics engine. Implementation barriers are categorized into five groups—technological, organizational, economic, infrastructural, and methodological—with interoperability issues, hardware performance limitations, and the lack of standardized BIM-to-XR workflows being particularly recurrent. The review contributes to the Construction 4.0 agenda by providing a consolidated map of XR applications, technologies, and barriers, and by highlighting enablers such as open data schemas and competency-based training programs. Future research should validate AI-assisted, bidirectional BIM–XR workflows in real projects, report cost–benefit metrics, and advance interoperability standards that integrate XR into broader Construction 4.0 strategies. Full article

Amid accelerating climate change, intensifying urban heat island effects, and rising public demand for livable, walkable streets, there is an urgent practical need for interpretable and actionable evidence on streetscape quality. Yet, research on streetscape quality has often relied on single data sources and linear models, limiting insight into multidimensional perception; evidence from temperate monsoon cities remains scarce. Using Tianjin’s main urban area as a case study, we integrate street-view imagery with remote sensing imagery to characterize satellite-derived environmental indicators at the point scale and examine the following five perceptual outcomes: comfort, aesthetics, perceived greenness, summer heat perception, and willingness to linger. We develop a three-step interpretable assessment, as follows: Elastic Net logistic regression to establish directional and magnitude baselines; Generalized Additive Models with a logistic link to recover nonlinear patterns and threshold bands with Benjamini–Hochberg false discovery rate control and binned probability calibration; and Shapley additive explanations to provide parallel validation and global and local explanations. The results show that the Green View Index is consistently and positively associated with all five outcomes, whereas Spatial Balance is negative across the observed range. Sky View Factor and the Building Visibility Index display heterogeneous forms, including monotonic, U-shaped, and inverted-U patterns across outcomes; Normalized Difference Vegetation Index and Land Surface Temperature are likewise predominantly nonlinear with peak sensitivity in the midrange. In total, 54 of 55 smoothing terms remain significant after Benjamini–Hochberg false discovery rate correction. The summer heat perception outcome is highly imbalanced: 94.2% of samples are labeled positive. Overall calibration is good. On a standardized scale, we delineate optimal and risk intervals for key indicators and demonstrate the complementary explanatory value of street-view imagery and remote sensing imagery for people-centered perceptions. In Tianjin, a temperate monsoon megacity, the framework provides reproducible, actionable, design-relevant evidence to inform streetscape optimization and offers a template that can be adapted to other cities, subject to local calibration. Full article

Mimotope-based immunoassays offer an eco-friendly alternative to chemically synthesized antigens for the quantitative analysis of small molecules, but their use for practical on-site and high-throughput residue monitoring remains limited. Herein, we report the selection, production, and application of a phage display–derived mimotope targeting an anti-uniconazole monoclonal antibody (UCZ-mAb), with the aim of developing two complementary immunoassays that enable sensitive, eco-friendly detection of UCZ residues in agricultural samples. A 12-mer phage-displayed peptide library was screened to identify UCZ-specific mimotopes, and a selected sequence was genetically fused to SpyTag and expressed in Escherichia coli to generate a SpyTagged mimotope. Leveraging the SpyCatcher/SpyTag self-assembly system, the SpyTagged mimotope was directionally conjugated onto SpyCatcher-functionalized time-resolved fluorescence beads (TRFBs) and subsequently used as a signal-labeled competitive antigen in a lateral flow immunoassay (LFIA) designed for rapid on-site screening. In parallel, a wash-free magnetic separation immunoassay (MSIA) suitable for green, high-throughput screening in routine laboratories was established using self-assembled mimotope-TRFB probes. The LFIA and MSIA exhibited half-maximal inhibitory concentrations (IC₅₀) of 3.70–6.72 μg/kg and 16.4–18.3 μg/kg, respectively, in real samples. Spiked-sample recoveries ranged from 91.1 to 107.8% for LFIA and 92.6–115.7% for MSIA, demonstrating acceptable accuracy and precision. These results indicate that the SpyTagged mimotope–based LFIA and MSIA provide complementary, reliable, and sensitive platforms for on-site screening and high-throughput monitoring of UCZ residues in agricultural samples, while avoiding the drawbacks associated with traditional chemical antigen synthesis. Full article

Fish display remarkable swimming capabilities through the coordinated interaction of the body and caudal fin, yet the potential role of a passively pitching tail in enhancing hydrodynamic performance remains unresolved. In this work, we evaluate the performance of a carangiform swimmer equipped with either an actively pitching tail or a passively pitching tail. High-fidelity fluid–structure interaction simulations are employed to assess how variations in joint stiffness, damping, and inertia influence thrust generation, power demand, and overall stability at two representative Reynolds numbers, 500 and 5000. The results reveal that actively pitching tails tend to generate greater thrust, while passively pitching tails deliver improved outcomes in terms of power demand at the lower Reynolds number. Larger pitching amplitudes contribute positively only when associated with higher swimming frequency; when produced by reduced inertia or more flexible joints, they lead to unfavorable effects. At the higher Reynolds number, active tails consistently outperform passive ones, although a small subset of passive cases still achieve favorable performance. Across all cases, a recurring balance emerges, with thrust production and power expenditure varying inversely. These findings clarify the hydrodynamic consequences of passive versus active tail motion and establish design principles for bio-inspired underwater vehicles, in which smaller swimmers may benefit from passive tail pitching, whereas larger swimmers are better served by active control. Full article

Background: Pregnancy-associated breast cancer (PABC), defined as breast cancer diagnosed during pregnancy or within one year postpartum, is a unique and clinically challenging entity. Evidence suggests that tumors diagnosed during pregnancy (PrBC) and postpartum (PPBC) may differ in biology and prognosis. This study compares clinical features, treatment patterns and outcomes between PrBC and PPBC. Methods: We performed a retrospective analysis of 76 women diagnosed with PABC from January 2000 to June 2023 across two tertiary centers. Patients were classified according to ESMO guidelines as PrBC (n = 41) or PPBC (n = 35). Clinical presentation, tumor characteristics, treatment approaches and survival outcomes were evaluated. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan–Meier analysis and compared with log-rank tests. Results: A total of 76 patients with PABC were included (41 PrBC, 35 PPBC; median age 37 years). Most tumors were high-grade invasive ductal carcinomas, with Luminal B predominant in PrBC and triple-negative breast cancer (TNBC) in PPBC. Locally advanced disease was common (axillary involvement 52%; de novo metastases 9%). Surgery was performed in most cases, with breast conservative surgery (BCS) more frequent in PrBC and mastectomy in PPBC; 46% received neoadjuvant chemotherapy. At median follow-up of 68 months, 7.9% of patients had died and 29% experienced recurrence. Oncologic outcomes were similar between subgroups, with a trend in favor of PrBC. Pregnancy continuation did not adversely affect outcomes. Conclusions: PrBC and PPBC display heterogeneous clinical presentations with a trend toward more favorable outcomes in PrBC. These findings support the need for tailored counseling, individualized management and research designs that differentiate between PrBC and PPBC. Full article

Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) is a dominant arthropod-borne disease in Asian countries. However, effective antiviral treatment for JEV has not yet been established. 2H4 is a previously identified mouse monoclonal antibody (mAb) which exhibited neutralizing activity against JEV infection. Herein, we designed a novel mAb F(ab’)₂ 2A10-2H4-CDR by transplanting the complementarity-determining regions (CDRs) of 2H4 into the corresponding regions of a murine mAb 2A10 which has high homology with human mAb. We further expressed the recombinant human–mouse chimeric mAb 2A10-2H4-CDR-hFc by linking 2A10-2H4-CDR with CH2 and CH3 domains of one human mAb. The results of indirect immunofluorescence assay and ELISA show that 2A10-2H4-CDR-hFc can recognize the E proteins of JEV and Zika virus (ZIKV), similar to its original form 2H4. Moreover, 2A10-2H4-CDR-hFc displayed neutralizing activities against JEV and ZIKV equivalent to that of 2H4 in vitro (NT₅₀ value against JEV = 0.079 μg/mL versus 0.022 μg/mL, respectively; NT₅₀ value against ZIKV = 1.584 μg/mL versus 0.446 μg/mL, respectively). Both 2H4 and 2A10-2H4-CDR-hFc significantly increased the survival and reduced the serum viral burden of mice challenged by JEV or ZIKV. This study successfully validates an anti-JEV and ZIKV human–mouse chimeric mAb and establishes a basis for future application of this Ab in preventing or/and treating of both JEV and ZIKV infections. Full article

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a central therapeutic target in Alzheimer’s disease, as it catalyzes the rate-limiting step in amyloid-β production. Verubecestat (VER), a clinical BACE1 inhibitor, failed in late-stage trials due to limited efficacy and safety concerns. This study employed an integrative computational approach to design VER derivatives with improved binding affinity, stability, and pharmacokinetic profiles. Structural similarity analysis, Molecular docking, frontier molecular orbital (FMO) analysis, pharmacophore modeling, 200 ns molecular dynamics (MD) simulations, MM/PBSA free energy calculations, and per-residue decomposition were performed. In silico ADMET profiling assessed drug-likeness, absorption, and safety parameters. Docking and pharmacophore analyses identified derivatives with stronger complementarity in the BACE1 catalytic pocket. MD simulations revealed that VERMOD-33 and VERMOD-57 maintained low root mean square deviations (RMSDs) and stable binding orientations and induced characteristic flexibility in the flap and catalytic loops surrounding the catalytic dyad (Asp93 and Asp289), consistent with inhibitory activity. MM/PBSA confirmed the superior binding free energies of VERMOD-33 (−51.12 kcal/mol) and VERMOD-57 (−43.85 kcal/mol), both outperforming native VER (−35.33 kcal/mol). Per-residue decomposition highlighted Asp93, Asp289, and adjacent flap residues as major energetic contributors. ADMET predictions indicated improved oral absorption, BBB penetration, and no mutagenicity or toxicity alerts. Rationally designed VER derivatives, particularly VERMOD-33 and VERMOD-57, displayed enhanced binding energetics, stable inhibitory dynamics, and favorable pharmacokinetic properties compared with native VER. These findings provide a computational framework for rescuing VER and support further synthesis and experimental validation of next-generation BACE1 inhibitors for Alzheimer’s disease. Full article

The search for multifunctional wound dressings that combine structural integrity with biological activity remains an important challenge in modern biomedicine. In this study, electrospun chitosan/polyethylene oxide (CS/PEO) nanofibers incorporating Centella asiatica extract were developed and evaluated in vitro as potential wound-healing materials. Nanofibers were fabricated using various CS/PEO ratios, and the 1:2 w/w composition loaded with 1% extract was selected as the optimal formulation based on morphological homogeneity and processing efficiency. Comprehensive characterization demonstrated that the nanofiber matrix provided sustained release of asiaticosides over several days, fitting best with Hixson–Crowell and Higuchi kinetic models, suggesting a combined diffusion–erosion mechanism. Biological assays confirmed that the optimized formulation displayed strong antioxidant and anti-inflammatory activity, with synergistic effects observed between chitosan and C. asiatica. Moreover, chitosan contributed intrinsic antimicrobial properties against Staphylococcus aureus and Klebsiella pneumoniae, while the extract provided additional antioxidant and regenerative potential. Biocompatibility studies in human fibroblasts showed no cytotoxic effects, and scratch assays confirmed that extract-loaded nanofibers significantly accelerated wound closure compared to the control and CS/PEO base. Taken together, the results highlight the potential of CS/PEO nanofibers with C. asiatica extract as multifunctional wound dressings that integrate structural support, controlled release, antimicrobial protection, and regenerative bioactivity. Future work should address in vivo evaluation, scale-up of electrospinning, and potential incorporation of synergistic antimicrobial agents to further enhance clinical applicability. This approach underlines the value of combining natural product pharmacology with biopolymer engineering in the design of next-generation wound-healing biomaterials. Full article