Search Results (31,611)

Nintedanib is an anti-fibrotic medication endowed with a multi-kinase inhibitor profile and approved for the treatment of Idiopathic Pulmonary Fibrosis (IPF). Nintedanib is believed to inhibit mainly Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), and Fibroblast Growth Factor (FGF) receptor kinases. The main objective was to identify potential tissue and/or circulating biomarkers to demonstrate Nintedanib’s target engagement and support its in vivo pharmacodynamic activity, consistent with its proposed mechanism(s) of action. In four independent experiments of bleomycin (BLM)-induced lung fibrosis model in rats, animals received Nintedanib (oral, 100 mg/kg/day) from day 7 post-BLM for 3 weeks. As expected, Nintedanib significantly reduced lung weight, the levels of lung fibrotic markers, and fibrotic areas. Moreover, Nintedanib-treated animals expressed lower levels of FGF2 in lung homogenates and higher plasma and lung levels of VEGF (≥3-fold, p < 0.05) compared to control animals. Lung proteomic analysis revealed the inhibition of receptor tyrosine kinases signaling in Nintedanib-treated animals. Circulating and lung levels of Nintedanib confirmed an optimal tissue distribution in the rat, consistent with the data reported for humans. Although VEGF ligand levels are elevated in the lungs of Nintedanib-treated animals, the VEGF signaling pathway remained functionally downregulated, strongly suggesting compensatory VEGF feedback delivery to its receptor blockade by Nintedanib. In summary, based on the present experimental findings in rats and supporting clinical preliminary evidence, increased VEGF levels can be reasonably considered an indicator of target engagement for Nintedanib and potentially for other VEGF modulators. Full article

Low reactivation efficiency of idle anaerobic ammonia oxidation (anammox) sludge hinders its reapplication. To address this issue, rape straw biochar (RSB) was added in the reactivation process of idle anammox sludge, and its effects on the nitrogen transformation and sludge characteristics were investigated, and the mechanism of RSB to enhance the reactivation performance was explored. Results indicated that adding 5 g/L RSB for 35 days successfully reactivated anammox sludge that had been idle for 270 days. The reactivation time was reduced by 34% compared to the control without RSB. During the stable operation period, the average TN removal efficiency reached 90.6%, and the sludge exhibited higher activity. After completion of reactivation, the specific surface area, total pore volume, and average pore diameter of RSB decreased by 59.4%, 66.9%, and 55.2%, respectively, compared with that before reactivation, and the carbon–oxygen functional groups also changed. RSB not only provided a habitat for the enriched growth of nitrogen transforming functional flora but also possessed the potential to supply sufficient electron donors and acceptors for the nitrogen transforming process, which promoted the synergistic removal of nitrate by denitrification, resulting in an effective enhancement of reactivation efficiency and nitrogen removal performance. The addition of RSB provides a novel strategy to enhance the reactivation efficiency of idle anammox sludge, which is of positive significance in promoting its efficient reuse and stable operation. Full article

Tomato brown rugose fruit virus (ToBRFV) has become a major threat to global tomato production due to its exceptional mechanical transmissibility and virion stability. Effective sanitation is essential for containment, yet the performance of commonly used disinfectants on greenhouse-relevant surfaces remains poorly characterized. This study evaluated multiple disinfectant formulations, applied by spraying or dipping, on polyethylene film, pruning shears, and human hands. After controlled inoculation with a standardized inoculum, treated surfaces were swabbed and extracts mechanically inoculated onto Nicotiana rustica L. Lesion number was visually quantified, and lesion area was measured using a computational image-analysis pipeline. Fifth-generation quaternary ammonium compounds (5°QAS) showed the highest virucidal activity on smooth, non-porous surfaces, reducing lesion numbers to fewer than 10 per leaf at 800–1000 ppm and maintaining infection severities below 1%. Glutaraldehyde at 500 ppm also performed strongly, achieving severities as low as 0.20% on plastic. Metallic pruning shears consistently retained infectious particles, with untreated controls exceeding 100 lesions per leaf and treated samples showing incomplete inactivation. Mechanical agents such as powdered milk and soap reduced infection but did not eliminate transmission. No clear dose–response trend was observed. The two most effective treatments, 5°QAS at 800–1000 ppm and glutaraldehyde at 500 ppm, significantly reduced or prevented systemic infection in tomato assays. These findings demonstrate that sanitation efficacy depends on formulation, surface type, and application method, providing operationally relevant guidelines for ToBRFV management. Full article

Background/Objectives: Appropriate imaging surveillance, established by the Society of Vascular Surgery (SVS), following endovascular aorta repair (EVAR) is critical for patient monitoring. We hypothesized that adherence to follow-up decreases over time, and therefore, the ability to detect endoleaks after EVAR also decreases. Methods: A retrospective cohort study of patients who underwent EVAR from 2014 to 2022 at our institution was completed. Patients were stratified by adherence to SVS guidelines for up to five years postoperatively. Demographics, detection of an endoleak > 30 days postoperatively, distance from our facility, and Area Deprivation Index (ADI) were collected. Comparisons of baseline comorbidities between groups and multivariate logistic regressions were performed using R studio. Results: 395 patients underwent an index EVAR at our institution from 2014–2022. 174 (44%) of patients adhered to all imaging recommendations, with an average loss to follow-up of 9.7% per year. 61 (15.4%) patients had a detected type II endoleak during the study period. Multivariable analysis identified residence > 50 miles from our institution as an independent risk factor for nonadherence (OR 1.76, p = 0.018) when controlling for age, sex, race, and ADI quartile. Conclusions: Adherence to surveillance guidelines gradually decreases after EVAR, but type II endoleak detection continues to occur years following the operation. While residence greater than 50 miles away was associated with nonadherence, patients’ ADI was not. Our results identify an opportunity for providers who may see patients more frequently to assist in reminding and arranging imaging follow-up for patients following their procedure. Full article

Arboviruses spread in urban tropics under climate change. At Aedes aegypti breeding sites in Recife, Brazil, we linked surveillance and climate data from the Pernambuco Water and Climate Agency (APAC), the Brazilian National Institute of Meteorology (INMET), Rapid Survey of Indices for Aedes aegypti (LIRAa), and Recife’s Open Data Portal. We modeled 2013–2021 cases and 2009–2017 breeding sites. We generated spatial fields with inverse distance weighting. We built bimonthly training grids with 5000 points and validation grids with 50,000 points. We tested linear regression, random forests, multilayer perceptrons, support vector regressors, and extreme learning machines in the Weka platform and Python Reservoir Computing Networks (PyRCNs). We ran 30 repetitions with cross-validation. The random forests performed well. Multilayer perceptrons reached very high correlations but needed longer training. Polynomial Support Vector Machines (SVMs) reached near-perfect accuracy but required very high computation. Single-layer extreme learning machines delivered the best trade-off, with low errors, correlations near 1.0, and short training times. The models produced fine-scale risk predictions and highlighted priority areas. The findings support earlier, targeted control and guide public health plans in Recife. Full article

The close spatial and genetic coexistence of Skarn-type and Hydrothermal Vein-type Pb-Zn deposits in the Shanghulin area, Inner Mongolia, poses a significant challenge to conventional “ undifferentiated” prediction models. This study aims to decouple these distinct metallogenic patterns using a data-driven, “type-specific modeling” strategy, establishing separate prediction models for Skarn-type and Hydrothermal Vein-type mineralization. Our workflow first employs Lasso–RFECV for rigorous pre-screening of over 60 geoscience features to identify the optimal predictive subset. Subsequently, an XGBoost model is trained on these selected features, and the SHAP framework is applied to interpret the geological significance of its decision logic. The results confirm two distinct indicator systems. (1) The Skarn-type model is controlled by spatial proximity to a heat source, heavily relying on Distance_to_Volcano and high-temperature indicators (CLR_Mo, CLR_W, CLR_Mn). (2) The Hydrothermal Vein-type model is “chemical fingerprint-driven”, prioritizing CLR_Y and identifying a complex “leaching-enrichment” pattern: mineralization requires simultaneous wall-rock leaching (low CLR_Al₂O₃, low CLR_Y) and specific metal enrichment (high CLR_Co, high CLR_Zn). This study confirms the controlling factors: Skarn-type deposits are governed by magmatic proximity, whereas Hydrothermal Vein-type deposits are defined by specific alteration geochemical signatures. The proposed “Lasso–RFECV → XGBoost → SHAP” workflow successfully decouples these independent, geologically meaningful prospectivity models from complex data, offering a new paradigm for precise exploration. Full article

This paper presents a discrete-time, centralized fractional-order linear quadratic regulator FOLQR for automatic generation control (AGC) of three-area interconnected nonreheat thermal systems. The AGC state explicitly includes the area control error (ACE) and tie-line power; a quadratic performance index penalizes ACE, its integral (IACE), and control effort. The continuous-time plant (governor–turbine dynamics and tie-line flows) is discretized at a fixed sampling interval, and a single centralized gain is obtained from the discrete algebraic Riccati equation; the fractional-order extension shapes memory in the feedback to temper rapid transients. Benchmark studies under $0.01$ and $0.05$ p.u. step-load disturbances show that FOLQR stabilizes the interconnection and consistently lowers peak excursions relative to a conventional discrete LQR (COQAGC) baseline—reducing frequency peaks by about 9–$12\%$ and tie-line peaks by 24–$60\%$ in the small-step case—while producing smoother actuator commands. Although FOLQR exhibits longer settling times, this trade-off is acceptable FOr multi-area AGC where limiting overshoot and tie-line excursions is operationally more critical than strict settling-time targets. The proposed controller retains a simple centralized, discrete-time structure with a modest computational burden, making it suitable FOr real-time AGC deployment in large interconnected grids and demonstrating for the first time, to our knowledge, a fractional-order LQR applied to a three-area thermal benchmark. Full article

The enrichment laws and key controlling factors of coalbed methane (CBM) in the Xishanyao Formation of the Hedong mining area remain unclear, restricting exploration progress. Based on well data and experimental analyses, this study investigates CBM enrichment characteristics and geological controls using genetic identification diagrams. Results demonstrate that CBM exhibits a “high in northwest and low in southeast” planar distribution. Vertically, CBM content is extremely low above 360 m due to weathering oxidation and burnt zone effects, increases within the 360–950 m interval (peaking at 750–950 m), and declines from 950 to 1200 m because of limited gas contribution. Genetic analysis indicates predominantly primary biogenic gas, with a minor component of early thermogenic gas. Enrichment is controlled by structure and hydrogeology: the medium-depth range (358–936 m) on the northern syncline limb and western part of the northern monoclinal zone forms a high-efficiency enrichment zone due to compressive stress from reverse faults and high mineralization groundwater (TDS > 8000 mg/L). While the southern limb, characterized by high-angle tensile fractures and active groundwater runoff, suffers gas loss and generally low gas content (<3.5 m³/t). This study clarifies CBM enrichment laws and enrichment mechanisms, supporting exploration of low-rank CBM in the Hedong mining area. Full article

Bacterial blight in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo), poses a serious threat to global rice production. The ability of Xoo to form biofilms is a key factor for its virulence. The OryR protein is a LuxR-type quorum-sensing regulator essential for biofilm formation and Xoo pathogenicity. However, the three-dimensional structure of OryR remains poorly understood. This study integrates homology modeling, molecular dynamics (MD) simulations, and virtual screening to elucidate the structure of OryR and identify potential inhibitors that target its ligand-binding domain. MD simulations confirmed the structural stability of OryR, and comparative analysis with experimentally determined structures of ligand- or inhibitor-bound homologs revealed a binding site in OryR with a distinct hourglass-like shape for long-range contacts. Virtual screening of over 200,000 compounds from four chemical libraries identified several promising inhibitor candidates, with the top compounds showing strong binding energies in both molecular mechanics-generalized Born surface area (−68.3 kcal/mol) and molecular mechanics Poisson–Boltzmann surface area (−19.3 kcal/mol) calculations. Overall, this study provides insights into the OryR structure and highlights potential inhibitors that can be developed as novel agents to control bacterial blight. However, additional experimental validations are required to refine and optimize these leads for drug development. Full article

Amidst the paradigm shift in park city development from quantitative metrics to spatial performance, urban complex parks—a novel green space type developed privately yet fulfilling public functions—present an innovative approach to park provision in high-density urban areas. However, systematic empirical evidence on their social value remains scarce. This study characterizes urban complex parks as a new form of green public space that provides key ecosystem services and proposes a three-dimensional evaluation framework integrating “usage vitality, place attractiveness, and user satisfaction.” Analyzing 19 park-equipped complexes among 75 cases in Shanghai using LBS data and online reviews through controlled linear regression and comparative analysis, our results indicate complexes with parks were associated with significantly outperforming others in place attractiveness and user satisfaction. Key findings include associations with a 413.7 m increase in average OD distance, a 3.4–4.0% higher city-level visitor share, and 5.24 percentage points greater median positive review rate. Crucially, spatial location outweighs green ratio and size in determining social value. Ground-level parks, through superior spatial integration, function as effective “social-ecological interfaces,” significantly outperforming rooftop parks in attracting long-distance visitors, stabilizing foot traffic (≈3% lower fluctuation), and enhancing per-store visitation. This demonstrates that green space quality (experiential quality and spatial configuration) matters more than quantity. Our findings suggest that urban complex parks can create social value through perceivable naturalness and restorative environments, providing an empirical basis for optimizing park city implementation in high-density contexts and highlighting the need to reconcile broad attractiveness with equitable local access. Full article

Alzheimer’s disease (AD) is marked by cognitive decline, and also by retinal degeneration. Having in mind that docosahexaenoic acid (DHA, 22:6n − 3) is a safe, low-cost, and pivotal fatty acid for brain health and sustained cognitive function, this study exploits environmentally friendly non-fish sources as potential dietary supplements enriched with DHA to prevent or reverse AD. Forty 5xFAD transgenic male mice, aged five weeks old, were randomly distributed by five body weight-matched dietary groups (with eight animals each) and fed isocaloric diets based on the AIN-93M standard formulation for rodents for 6 months. Except for the control feed (without supplementation), each diet contained a modified lipidic fraction supplemented with 2% of the following: (1) linseed oil (LSO, rich in alpha-linolenic acid (ALA, 18:3n − 3)); (2) cod liver oil (fish oil, FO, rich in both DHA and eicosapentaenoic acid (EPA, 20:5n − 3)); (3) Schizochytrium sp. microalga oil (Schizo, with 40% of DHA); and (4) commercial DHASCO (DHASCO, with 70% of DHA). The aim of this study was to measure retinal neural layer thickness, calculate ganglion cell layer (GCL) density, and assess retinal injury by means of immunohistochemical staining for β-amyloid plaques deposition, TAU protein levels, and IBA1, as hallmark features of AD progression, in order to elucidate the effects of different dietary DHA treatments in Alzheimer’s retinas. Although no statistical differences were observed across retinal layer thicknesses depending on the diet (p > 0.05), there was a consistent pattern for slightly increased retinal thickness in 5xFAD mice fed fish oil relative to the others for the measurement of total layers, in general and for the inner segment/outer segment layer, the outer nuclear layer, the outer plexiform layer, the inner nuclear layer, and the inner plexiform layer, in particular. The ganglion cell layer (GCL) density was increased in 5xFAD mice fed the DHASCO oil diet relative to the control (p < 0.05), suggesting a benefit of DHA supplementation on the number of viable ganglion cells. No positive staining was observed for β-amyloid plaques deposition or the neuroinflammatory marker, IBA1, corroborating previous findings in human AD retinas. Conversely, the internal retinal layers showed intense TAU immunostaining. Immnunostained TAU area was significantly reduced in 5xFAD mice fed a fish oil diet compared to control (p < 0.05), although the number of TAU-positive cells did not differ across diets (p > 0.05). The retinal protected integrity derived from the benefits of DHA supplementation found, either from fish oil or DHASCO oil, underscores the potential of retinal biomarkers as non-invasive indicators of cognitive decline and overall brain health, opening new avenues for investigating AD pathophysiology in the retina. Full article

The giant freshwater prawn Macrobrachium rosenbergii is a globally farmed decapod species of high economic and nutritional value, but its genetic improvement has been constrained by the lack of an efficient genome editing workflow. Here, we optimized a CRISPR/Cas9 microinjection system for targeted mutagenesis in M. rosenbergii embryos. A controlled mating-based approach enabled routine collection of one-cell embryos, and developmental staging identified 0.5–2 h post-fertilization as the optimal injection window. Optimization of the needle tip (~1 μm) minimized mechanical damage, lowering early embryo mortality to ~10%. Using this system, the eye-development gene MrPAX6 and the sex-related gene MrIAG were successfully edited. MrPAX6 editing produced a 46.9% mutation rate and an average 50% reduction in eye pigment area. MrIAG editing achieved an 84% mutation rate, while post-injection survival to hatching was approximately 35%. These results establish an efficient and reproducible CRISPR/Cas9 editing system in M. rosenbergii, providing a foundation for functional genomics and genetic improvement in this commercially important prawn species. Full article

With global climate changing, numerous cities have a rise in the frequency of heavy rainfall events. Concurrently, the rapid urbanization is increasing the impermeable surfaces, heightening the vulnerability to cope with flooding of urban stormwater drainage systems. This work compared the different retention strategies to mitigate flooding risks by simulating various scenarios using StormDesk 2.0. Additionally, it conducts multi-objective optimization of retention volume reduction, overflow volume reduction, and cost constraints through NSGA-II to obtain adaptation schemes across diverse scenarios. The findings demonstrate that, compared with the maximum area and overflow reduction ratio schemes, the drainage capacity can increase 15% under the adaptation scheme. Furthermore, the investment of the adaptation scheme is the most economical, at 10.59% of the maximum area scheme, and the overflow reduction surpasses that of the maximum area scheme by 45.8%. The most economical unit control cost in the adaptation scheme was USD 64.2/m³, while the full cost reached USD 277,337.9, highlighting its superior cost-benefit. The above results can provide a paradigmatic reference for enhancing stormwater drainage capacity in urban built-up areas. Full article

Member 2 of the Xujiahe Formation in the Anyue area of the Sichuan Basin exhibits significant resource potential for tight sandstone gas. However, its characteristic of “extensive gas presence with localized enrichment” leads to substantial variations in single-well productivity, challenges in target zone optimization, and unclear enrichment mechanisms, which hinder efficient exploration and development. This study proposes a hierarchical classification scheme of “two-level, six-type” source–reservoir structures based on the developmental characteristics of fault–fracture systems and vertical source–reservoir configurations. The gas-bearing heterogeneity is quantitatively characterized using parameters such as effective gas layer thickness, charge intensity, and effective gas layer probability, thereby revealing the differential enrichment mechanisms of tight sandstone gas controlled by source–reservoir structures. Our key findings include the following: (1) Member 2 of the Xujiahe Formation develops six subtypes of source–reservoir structures grouped into two levels, with gas-bearing capacities ranked as follows: source–reservoir separation type > source–reservoir adjacent type I > source–reservoir adjacent type II. Among these, the source–reservoir separation type (Level I) and fault–fracture conduit type (Level II) represent the most favorable structures for gas enrichment. (2) Tight sandstone gas enrichment is governed by a tripartite synergistic mechanism: hydrocarbon supply from source rocks, vertical cross-layer migration dominated by fault–fracture systems, and reservoir storage capacity determined by fracture density and reservoir thickness. (3) Three enrichment models are established: (i) a strong enrichment model characterized by “multi-layer source rocks beneath the reservoir, cross-layer migration, and thick fractured reservoirs”; (ii) a moderate enrichment model defined by “single-layer source rocks, localized migration, and medium-thick fractured reservoirs”; and (iii) a weak enrichment model featuring “single-layer hydrocarbon supply, pore-throat migration, and thin tight reservoirs.” This research provides a theoretical basis for optimizing exploration targets in Member 2 of the Xujiahe Formation in the Anyue area and offers insights applicable to analogous continental tight gas reservoirs. Full article

Graphene oxide (GO), with its high surface area, tunable chemistry, and exceptional mechanical, thermal, and electrical properties, is rapidly advancing as a transformative material in both composite engineering and membrane technology. In composite systems, GO serves as a multifunctional reinforcement, significantly improving strength, stiffness, thermal stability, and conductivity when integrated into polymeric, ceramic, or metallic matrices. These enhancements are enabling high-performance solutions across electronics, aerospace, automotive, and construction sectors, where lightweight yet durable materials are in demand. In addition, GO-based membranes are revolutionizing water purification, desalination, and other high-end separation technologies. The layered structure, adjustable interlayer spacing, and abundant oxygen-containing functional groups of GO allow precise control over permeability and selectivity, enabling efficient transport of desired molecules while blocking contaminants. Tailoring GO morphology and surface chemistry offers a pathway to optimized membrane performance for both industrial and environmental applications. This paper gives a comprehensive overview of the latest developments in GO-based composites and membranes, highlighting the interplay between structure, morphology, and functionality. Future research directions toward scalable fabrication, performance optimization, and integration into sustainable technologies are discussed, underscoring GO’s pivotal role in shaping next-generation advanced materials. Full article