Search Results (15,059)

A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function. Full article

Climate change is generally having a negative impact on forest health by inducing drought stress and favouring the spread of pest species, such as bark beetles. The terrestrial monitoring of bark beetle infestation is very time-consuming, especially in the early stages, and therefore not feasible for extensive areas, emphasising the need for a comprehensive approach based on remote sensing. Although numerous studies have researched the use of optical data for this task, radar data remains comparatively underexplored. Therefore, this study uses the weekly and cloud-free acquisitions of Sentinel-1 in the Bavarian Forest National Park. Time series analysis within a Multi-SAR framework using Random Forest enables the monitoring of moisture content loss and, consequently, the assessment of tree vitality, which is crucial for the detection of stress conditions conducive to bark beetle outbreaks. High accuracies are achieved in predicting future bark beetle infestation (R² of 0.83–0.89). These results demonstrate that forest vitality trends ranging from healthy to bark beetle-affected states can be mapped, supporting early intervention strategies. The standard deviation of 0.44 to 0.76 years indicates that the model deviates on average by half a year, mainly due to the uncertainty in the reference data. This temporal uncertainty is acceptable, as half a year provides a sufficient window to identify stressed forest areas and implement targeted management actions before bark beetle damage occurs. The successful application of this technique to extensive test sites in the state of North Rhine-Westphalia proves its transferability. For the first time, the results clearly demonstrate the expected relationship between radar backscatter expressed in the Kennaugh elements K₀ and K₁ and bark beetle infestation, thereby providing an opportunity for the continuous and cost-effective monitoring of forest health from space. Full article

The accumulation of end-of-life tires and the rapid increase in demolition activities pose significant environmental and waste-management challenges. The redevelopment of construction materials incorporating this waste is a potentially promising strategy for minimizing environmental impact while promoting the principles of a circular economy. This study investigates the performance of self-compacting concrete (SCC) incorporating up to 20% rubber aggregates (sand and gravel) and 40% recycled concrete aggregate (RCA) for non-structural applications. A series of tests was conducted to assess fresh and hardened properties, including flowability, compressive strength, tensile strength, flexural strength, water absorption, and density. The results indicated that increasing RCA content reduced density and compressive strength, while tensile and flexural strengths were only moderately affected. Response surface methodology (RSM), utilizing a Box–Behnken design, was employed to optimize compressive, tensile, and flexural strength responses. Statistical analysis was used to identify the optimal mix proportions, which balance the mechanical performance and sustainability of SCC with recycled components. Mixtures incorporating moderate rubber content—specifically, 5–5.5% sand rubber and 0–6% coarse rubber—and 40% recycled-concrete aggregate (RCA) achieved the highest predicted performance, with compressive strength ranging from 20.00 to 28.26 MPa, tensile strength from 2.16 to 2.85 MPa, and flexural strength reaching 5.81 MPa, making them suitable for sidewalks and walkways. Conversely, mixtures containing higher rubber proportions (5.5–20% sand rubber and 20% coarse rubber) combined with the same RCA level (40%) showed the lowest mechanical performance, with compressive strength between 5.2 and 10.08 MPa, tensile strength of 1.05–1.41 MPa, and flexural strength from 2.18 to 3.54 MPa. These findings underscore the broad performance range achievable through targeted optimization. They confirm the viability of recycled materials for producing environmentally friendly SCC in non-structural applications. Full article

Papillomaviruses (PVs) are double-stranded DNA viruses known to induce a variety of epithelial lesions in dogs, ranging from benign hyperplasia to malignancies. In regions of rich biodiversity such as the Western Amazon, data on the circulation and genetic composition of canine papillomaviruses (CPVs) remain scarce. This study investigated CPV types present in oral and cutaneous papillomatous lesions in domiciled dogs from Acre and Rondônia States, Brazil. Sixty-one dogs with macroscopically consistent lesions were clinically evaluated, and tissue samples were collected for histopathological examination and PCR targeting the L1 gene. Among these, 37% were histologically diagnosed as squamous papillomas or fibropapillomas, and 49.2% (30/61) tested positive for papillomavirus DNA. Sequencing of the L1 gene revealed that most positive samples belonged to CPV1 (Lambdapapillomavirus 2), while one case was identified as CPV8 (Chipapillomavirus 3). Complete genomes of three CPV1 strains were obtained via high-throughput sequencing and showed high identity with CPV1 strains from other Brazilian regions. Phylogenetic analysis confirmed close genetic relationships among isolates across distinct geographic areas. These findings demonstrate the circulation of genetically conserved CPVs in the Amazon and reinforce the value of molecular and histopathological approaches for the accurate diagnosis and surveillance of viral diseases in domestic dogs, especially in ecologically complex regions. Full article

Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes. Full article

This communication presents an accurate and computationally efficient approach for wideband radar cross-section (RCS) estimation and scattering point reconstruction using infinitesimal dipole modeling (IDM) with compressive sensing. The proposed method eliminates the need for field sampling at numerous frequency points across the wideband range through Green’s function adjustment. Additionally, compressive sensing is employed for induced current calculation to reduce both frequency and angular sampling requirements. Numerical validation demonstrates that the method achieves a 50% reduction in field sample data and an 82.3% reduction in IDM processing time while maintaining comparable accuracy through Green’s function adjustment. Furthermore, compared to approaches without compressive sensing, the method shows a 55.1% and a 75.5% reduction in error in averaged RCS for VV-pol and HH-pol, respectively. The proposed method facilitates efficient wideband RCS estimation of various targets while significantly reducing measurement complexity and computational cost. Full article

Lactic acid bacteria (LAB) are central to food, feed, and health biotechnology, yet their genomes have long resisted rapid, precise manipulation. This review charts the evolution of LAB genome-editing strategies from labor-intensive RecA-dependent double-crossovers to state-of-the-art CRISPR and CRISPR-associated transposase systems. Native homologous recombination, transposon mutagenesis, and phage-derived recombineering opened the door to targeted gene disruption, but low efficiencies and marker footprints limited throughput. Recent phage RecT/RecE-mediated recombineering and CRISPR/Cas counter-selection now enable scar-less point edits, seamless deletions, and multi-kilobase insertions at efficiencies approaching model organisms. Endogenous Cas9 systems, dCas-based CRISPR interference, and CRISPR-guided transposases further extend the toolbox, allowing multiplex knockouts, precise single-base mutations, conditional knockdowns, and payloads up to 10 kb. The remaining hurdles include strain-specific barriers, reliance on selection markers for large edits, and the limited host-range of recombinases. Nevertheless, convergence of phage enzymes, CRISPR counter-selection and high-throughput oligo recombineering is rapidly transforming LAB into versatile chassis for cell-factory and therapeutic applications. Full article

Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)₂₀) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article

This study aims to enhance the performance of an innovative steel slag–ceramsite foam concrete (SSCFC) to advance sustainable green building materials. An eco-friendly composite construction material was developed by integrating industrial by-product steel slag (SS) with lightweight ceramsite. Employing a three-factor, three-level orthogonal experimental design at a fixed density of 800 kg/m³, 12 mix proportions (including a control group) were investigated with the variables of water-to-cement (W/C) ratio, steel slag replacement ratio, and ceramsite replacement ratio. The governing mechanisms of the W/C ratio, steel slag replacement level, and ceramsite replacement proportion on the SSCFC’s fluidity and compressive strength (CS) were elucidated. The synergistic application of range analysis and analysis of variance (ANOVA) quantified the significance of factors on target properties, and partial least squares regression (PLSR)-based prediction models were established. The test results indicated the following significance hierarchy: steel slag replacement > W/C ratio > ceramsite replacement for fluidity. In contrast, W/C ratio > ceramsite replacement > steel slag replacement governed the compressive strength. Verification showed R² values exceeding 65% for both fluidity and CS predictions versus experimental data, confirming model reliability. Multi-criteria optimization yielded optimal compressive performance and suitable fluidity at a W/C ratio of 0.4, 10% steel slag replacement, and 25% ceramsite replacement. Full article

pH is a critical parameter requiring precise monitoring across scientific, industrial, and biological domains. Fluorescent pH probes offer a powerful alternative to traditional methods (e.g., electrodes, indicators), overcoming limitations in miniaturization, long-term stability, and electromagnetic interference. By utilizing photophysical mechanisms—including intramolecular charge transfer (ICT), photoinduced electron transfer (PET), and fluorescence resonance energy transfer (FRET)—these probes enable high-sensitivity, reusable, and biocompatible sensing. This review systematically details recent advances, categorizing probes by operational pH range: strongly acidic (0–3), weakly acidic (3–7), strongly alkaline (>12), weakly alkaline (7–11), near-neutral (6–8), and wide-dynamic range. Innovations such as ratiometric detection, organelle-specific targeting (lysosomes, mitochondria), smartphone colorimetry, and dual-analyte response (e.g., pH + Al³⁺/CN⁻) are highlighted. Applications span real-time cellular imaging (HeLa cells, zebrafish, mice), food quality assessment, environmental monitoring, and industrial diagnostics (e.g., concrete pH). Persistent challenges include extreme-pH sensing (notably alkalinity), photobleaching, dye leakage, and environmental resilience. Future research should prioritize broadening functional pH ranges, enhancing probe stability, and developing wide-range sensing strategies to advance deployment in commercial and industrial online monitoring platforms. Full article

The quality of water in households can be affected by plumbing design and materials, water usage patterns, and source water quality characteristics. These factors influence stagnation duration, disinfection residuals, metal release, and microbial activity. In particular, stagnation can degrade water quality and increase lead release from lead service lines. This study employs numerical modeling to assess how combined corrosion control and flushing strategies affect lead levels in household taps with lead service lines under reduced water use. To estimate potential health risks, the U.S. EPA model is used to predict the percentage of children likely to exceed safe blood lead levels. Lead exceedances are assessed based on various regulatory requirements. Results show that exceedances at the kitchen tap range from 3 to 74% of usage time for the 5 µg/L standard, and from 0 to 49% for the 10 µg/L threshold, across different scenarios. Implementing corrosion control treatment in combination with periodic flushing proves effective in lowering lead levels under the studied low-consumption scenarios. Under these conditions, the combined strategy limits lead exceedances above 5 µg/L to only 3% of usage time, with none above 10 µg/L. This demonstrates its value as a practical short-term strategy for households awaiting full pipe replacement. Targeted flushing before peak water use reduces the median time that water remains stagnant in household pipes from 8 to 3 h at the kitchen tap under low-demand conditions. Finally, the risk model indicates that the combined approach can reduce the predicted percentage of children with blood lead levels exceeding 5 μg/dL from 61 to 6% under low water demand. Full article

Silvopastoral systems, though ecologically beneficial, remain underrepresented in the European Union’s Common Agricultural Policy and are seldom studied in Mediterranean contexts. The current study assesses both the environmental and economic aspects of five typical silvopastoral systems in central Greece, encompassing cattle, sheep, and goat farming. A Life Cycle Assessment approach was implemented to quantify greenhouse gas emissions using economic allocation, distributing impacts between milk and meat outputs. Enteric fermentation was the major emission source, accounting for up to 65.14% of total emissions in beef-based systems, while feeding and soil emissions were more prominent in mixed and small ruminant systems. Total farm-level emissions ranged from 60,609 to 273,579 kg CO₂eq per year. Economically, only beef-integrated systems achieved an average annual profitability above EUR 20,000 per farm, based on financial data averaged over the last five years (2020–2024) from selected case studies in central Greece, while the remaining systems fell below the national poverty threshold for an average household, underscoring concerns about their economic viability. The findings underline the dual challenges of economic viability and policy neglect, stressing the need for targeted support if these multifunctional systems are to add value to EU climate goals and rural sustainability. Full article

To enable the practical application of passive back-support exoskeletons employing pneumatic artificial muscles (PAMs) in tasks such as agricultural work, we evaluated their assistive effectiveness in a half-squatting posture with a staggered stance. In this context, assistive force profiles were adjusted according to body posture to achieve more effective support. The targeted assistive force profile was designed to be continuously active from the standing to the half-squatting position, with minimal variation across this range. The assistive force profile was developed based on a PAM contractile force model and implemented using a cam mechanism. The effectiveness of assistance was assessed by measuring body flexion angles and erector spinae muscle activity during lifting and carrying tasks. The results showed that the assistive effect was greater on the side with the forward leg. Compared to the condition without exoskeleton assistance, the conventional pulley-based system reduced muscle activity by approximately 20% whereas the cam-based system achieved a reduction of approximately 30%. Full article

This research considers a preliminary comparative technical evaluation of two micro-gas turbine (MGT) systems in combined heat and power (CHP) mode (100 kWe), aimed at supplying heat to a residential community of 15 average-sized buildings located in Central Europe over a year. Two systems were modelled in Ebsilon 15 software: a natural gas case (benchmark) and an ammonia-fueled case, both based on the same on-design parameters. Off-design simulations evaluated performance over variable ambient temperatures and loads. Idealized, unrecuperated cycles were adopted to isolate the thermodynamic impact of the fuel switch under complete combustion assumption. Under these assumptions, the study shows that the ammonia system produces more electrical energy and less excess heat, yielding marginally higher electrical efficiency and EUF (26.05% and 77.63%) than the natural gas system (24.59% and 77.55%), highlighting ammonia’s utilization potential in such a context. Future research should target validating ammonia combustion and emission profiles across the turbine load range, and updating the thermodynamic model with a recuperator and SCR accounting for realistic pressure losses. Full article

Urban parks play an essential role in mitigating the urban heat island (UHI) effect driven by urbanization. A rigorous understanding of the cooling effects of urban parks can support urban planning efforts aimed at mitigating the UHI effect and enhancing urban sustainability. However, previous research has primarily focused on the maximum cooling impact, often overlooking the accumulative effects arising from spatial continuity. The present study fills this gap by investigating 74 urban parks located in the central area of Jinan and constructing a comprehensive cooling evaluation framework through two dimensions: maximum impact (Park Cooling Area, PCA; Park Cooling Efficiency, PCE) and cumulative impact (Park Cooling Intensity, PCI; Park Cooling Gradient, PCG). We further systematically examined the influence of park attributes and the surrounding urban structures on these metrics. The findings indicate that urban parks, as a whole, significantly contribute to lowering the ambient temperatures in their vicinity: 62.3% are located in surface temperature cold spots, reducing ambient temperatures by up to 7.77 °C. However, cooling intensity, range, and efficiency vary significantly across parks, with an average PCI of 0.0280, PCG of 0.99 °C, PCA of 46.00 ha, and PCE of 5.34. For maximum impact, PCA is jointly determined by park area, boundary length, and shape complexity, while smaller parks generally exhibit higher PCE—reflecting diminished cooling efficiency at excessive scales. For cumulative impact, building density and spatial enclosure degree surrounding parks critically regulate PCI and PCG by influencing cool-air aggregation and diffusion. Based on these findings, this study classified urban parks according to their cooling characteristics, clarified the functional differences among different park types, and proposed targeted recommendations. Full article