Search Results (52,786)

Astrocytes and microglia constitute nearly half of all central nervous system cells and are indispensable for its proper function. Both exhibit striking morphological and functional heterogeneity, adopting either neuroprotective (A2, M2) or proinflammatory (A1, M1) phenotypes in response to cytokines, pathogen-associated molecular patterns (PAMPs)/damage-associated molecular patterns (DAMPs), toll-like receptor 4 (TLR4) activation, and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling. Crucially, many of these phenotypic transitions arise during the earliest stages of neurodegeneration, when glial dysfunction precedes overt neuronal loss and may act as a primary driver of disease onset. This review critically examines glial-centered hypotheses of neurodegeneration, with emphasis on their roles in early disease phases: (i) microglial polarization from an M2 neuroprotective state to an M1 proinflammatory state; (ii) NLRP3 inflammasome assembly via P2X purinergic receptor 7 (P2X7R)-mediated K⁺ efflux; (iii) a self-amplifying astrocyte–microglia–neuron inflammatory feedback loop; (iv) impaired microglial phagocytosis and extracellular-vesicle–mediated propagation of β-amyloid (Aβ) and tau; (v) astrocytic scar formation driven by aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP)/vimentin, connexins, and janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling; (vi) cellular reprogramming of astrocytes and NG2 glia into functional neurons; and (vii) mitochondrial dysfunction in glia, including Dynamin-related protein 1/Mitochondrial fission protein 1 (Drp1/Fis1) fission imbalance and dysregulation of the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Sirt1/PGC-1α) axis. Promising therapeutic strategies target pattern-recognition receptors (TLR4, NLRP3/caspase-1), cytokine modulators (interleukin-4 (IL-4), interleukin-10 (IL-10)), signaling cascades (JAK2–STAT, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase–protein kinase B (PI3K–AKT), adenosine monophosphate-activated protein kinase (AMPK)), microglial receptors (triggering receptor expressed on myeloid cells 2 (TREM2)/spleen tyrosine kinase (SYK)/ DNAX-activating protein 10 (DAP10), siglec-3 (CD33), chemokine C-X3-C motif ligand 1/ CX3C motif chemokine receptor 1 (CX3CL1/CX3CR1), Cluster of Differentiation 200/ Cluster of Differentiation 200 receptor 1 (CD200/CD200R), P2X7R), and mitochondrial biogenesis pathways, with a focus on normalizing glial phenotypes rather than simply suppressing pathology. Interventions that restore neuroglial homeostasis at the earliest stages of disease may hold the greatest potential to delay or prevent progression. Given the complexity of glial phenotypes and molecular isoform diversity, a comprehensive, multitargeted approach is essential for mitigating Alzheimer’s disease and related neurodegenerative disorders. This review not only synthesizes pathogenesis but also highlights therapeutic opportunities, offering what we believe to be the first concise overview of the principal hypotheses implicating glial cells in neurodegeneration. Rather than focusing on isolated mechanisms, our goal is a holistic perspective—integrating diverse glial processes to enable comparison across interconnected pathological conditions. Full article

Objectives: Polymethyl methacrylate (PMMA) bone cement is vital for prosthetic fixation in orthopedic surgery, yet its exothermic polymerization can exceed 80 °C, surpassing the 50 °C threshold for thermal osteonecrosis, risking implant failure. This pilot study assesses two cooling strategies—precooling cement components and saline irrigation on the polymerization temperature and compressive strength of antibiotic-loaded PMMA, comparing hand mixing (HM) and vacuum mixing (VM) to optimize thermal management while preserving mechanical integrity in controlled settings relevant to orthopedic applications. Methods: Antibiotic-loaded Simplex bone cement (Stryker, Kalamazoo, MI, USA) was prepared using HM and VM, per ISO 5833. Each batch was divided into three groups: control, precooled (components at 6 °C overnight), and saline irrigation (8 °C saline during setting). Each group included 20 cylindrical samples (1.5 cm × 3 cm), cured for 24 h. Core temperatures were monitored with embedded thermometers, and compressive strength was measured in megapascals (MPa) using a hydraulic press (C092-06, MATEST). Welch’s t-test was used for statistical analysis. Results: HM controls reached 76.2 °C, precooled 63.6 °C, and saline 66 °C; VM controls hit 71.8 °C, precooled 58.8 °C, and saline 63.6 °C. HM strengths were 16–17 MPa, with precooling reducing to 16.49 MPa (p = 0.051) and saline maintaining 17.07 MPa (p = 0.820). VM strengths were 76–80 MPa, with precooling at 78.45 MPa (p < 0.001) and saline at 76.77 MPa (p = 0.010). Failure modes varied: controls (uniform cracking), precooled (shear failure), and saline (mixed cracking/crumbling). Conclusions: Precooling significantly lowers temperatures but compromises strength in HM samples, limiting its use in load-bearing applications. Saline irrigation offers moderate thermal control while preserving mechanics, particularly in HM, suggesting a viable strategy for reducing thermal necrosis risk. VM ensures superior strength, supporting safe cooling application. Full article

Metallic interconnects are key components in planar solid oxide fuel cell (SOFC) stacks. In the present study, we evaluated four Fe-Cr powder metallurgy (PM) alloy specimens, obtained from a domestic manufacturer, at nominal compositions (in wt%) of 5% Fe-95% Cr, 30% Fe-70% Cr, 50% Fe-50% Cr, and 78% Fe-22% Cr. These specimens were tested and evaluated for use in SOFC stack applications. The verification items included coefficient of thermal expansion measurements, high-temperature oxidation resistance and weight gain tests, mechanical strength tests, high-temperature sealant bonding and leakage rate measurements, and high-temperature electrical property (i.e., area-specific resistance) measurements. In addition, the specimens’ microstructures and elemental compositions were observed and analyzed. The test results indicate that the Fe content of the Fe-Cr powder metallurgy alloys influences various properties, while Cr also plays a significant role in high-temperature oxidation resistance. Among the four alloy specimens, the 78Fe-Cr alloy exhibited all of the aforementioned advantages, including a suitable coefficient of thermal expansion of 12.4 × 10⁻⁶/°C, excellent high-temperature oxidation resistance, a thermal weight-gain rate of 5.31 × 10⁻¹⁴ g²/cm⁴·s, a remarkably low high-temperature area-specific resistance of 7.04 mΩ·cm², and superior bonding and interfacial stability with the GC9 glass–ceramic sealant, achieving a very low leakage rate of 3.47 × 10⁻⁶ mbar·l/s/cm. These results indicate that the 78Fe-Cr powder metallurgy alloy performs excellently and is the most promising candidate for metallic interconnects in SOFC stack applications. Full article

Among the important differential equations on a Riemannian space $\left(M,g\right)$ of dimension n are the static perfect fluid equation (SPFE), namely $fRic-Hess\left(f\right)={\displaystyle \frac{1}{n}}\left(f\tau -\Delta f\right)g$, and the Fischer–Marsden equation (FME), namely $\left(\Delta f\right)g+fRic=Hess\left(f\right)$, where $Ric$ is the Ricci tensor, $\tau$ is the scalar curvature of $\left(M,g\right)$ and $Hess\left(f\right)$ and $\Delta f$ are the Hessian and the Laplacian of the smooth function f. The trace of the FME is $\Delta f=-{\displaystyle \frac{\tau }{n-1}}f$, which we call the TFME, and if we combine the TFME with the SPFE, we observe that it reduces to the FME. Thus, in the presence of the TFME on the Riemannian space $\left(M,g\right)$ the fundamental differential equations SPFE and FME are equivalent. In this article, we consider the presence of the TFME on a Riemannian space $\left(M,g\right)$ and study its impact on the Riemannian space $\left(M,g\right)$. The importance of this study follows from the fact that results obtained for Riemannian spaces admitting solutions to the TFME automatically are generalizations of corresponding results on spaces admitting solutions to the FME. First, we show that for a connected and compact Riemannian space $(M,g)$, $dimM=n>1$, with scalar curvature $\tau$ that admits a nontrivial solution f to the TFME, with the Ricci operator Q satisfying $Q\left(\nabla f\right)={\displaystyle \frac{\tau }{n}}\nabla f$, and with the integral of $Ric\left(\nabla f,\nabla f\right)$ having a suitable lower bound, it is necessary and sufficient that $(M,g)$ is an n-sphere ${\mathbf{S}}^n\left(c\right)$. In addition, we show that a compact and connected space $(M,g)$, $dimM=n>1$, admits a nontrivial solution f to the TFME such that the scalar curvature $\tau$ satisfies $(n-1)c<\tau \le n(n-1)c$ for some constant $c>0$, and the Ricci curvature $Ric(\nabla f,\nabla f)$ is bounded below by $(n-1)c$, if and only if $(M,g)$ is an n-sphere ${\mathbf{S}}^n\left(c\right)$. Finally, it is shown that a connected and compact Riemannian space $(M,g)$, $dimM=$$n>1$, with constant scalar curvature $\tau$ admits a nontrivial solution f to the TFME, with the Ricci operator Q satisfying $Q\left(\nabla f\right)={\displaystyle \frac{\tau }{n}}\nabla f$, if and only if $(M,g)$ is the sphere ${\mathbf{S}}^n\left(c\right)$. Full article

This study presents a versatile single-phase multilevel inverter designed to accommodate varying input voltages and output levels. Unlike conventional fixed topologies, the proposed design utilizes a unified structure of 13 switches and three capacitors to realize two distinct configurations: a nine-level circuit employing three series-connected single-voltage clamping sets, and a thirteen-level variant utilizing a hybrid of single- and half-voltage clamping sets. A critical advantage of this architecture is its capability to achieve capacitor self-voltage balancing within a single AC cycle, thereby simplifying the control strategy. Verification through PSIM 9.1 simulations and a TI F280025C-based hardware prototype confirms the circuit’s operational effectiveness. Notably, the thirteen-level configuration demonstrates superior performance, achieving a total harmonic distortion (THD) of 1.25% and a peak efficiency of 97.5%, significantly outperforming the 1.43% THD and 94.5% efficiency of the nine-level counterpart. Full article

The consolidation of mural paintings presents a significant challenge for conservators, as the treatments applied must not only be effective but also preserve the aesthetic qualities of the artwork. Ongoing research focuses on developing new products that are more efficient, durable, and compatible with the physicochemical and aesthetic characteristics of the original materials, thereby addressing the limitations of existing consolidants. This study examines two consolidants for mural painting restoration: Estel 1200^® (C.T.S., Madrid, Spain), a commercially available and widely used ethyl silicate-based product, and Nanorepair UV^® (Patent: ES-2766074-B2, Pablo de Olavide University, Seville, Spain), a nanocomposite composed of calcium hydroxide nanoparticles doped with zinc quantum dots. On mortar specimens, prepared according to the Roman fresco technique, the application method for the proposed treatments was optimized. The applicability of the treatments for mural painting conservation was studied by colorimetric measurements and SEM imaging to detect and characterize the formation of surface layers. The effectiveness of the treatments was quantitatively evaluated with tape-peeling cycles. The results show that, although both treatments enhance the consolidation state of mural paintings, Nanorepair UV^® proved to be a more effective consolidant, without altering the aesthetic or physicochemical properties of the artwork. Additionally, this treatment allows for straightforward evaluation of its penetration and enables distinction between treated and untreated areas through the fluorescence of the zinc oxide quantum dots. Full article

Background: Hemoglobin Rothschild (Hb Rothschild), NM_000518.5(HBB):c.112T>C, is an ultra-rare low-oxygen-affinity hemoglobin variant that persistently causes reduced peripheral oxygen saturation on pulse oximetry despite normal arterial oxygenation. Fewer than ten cases have been reported worldwide, and only one involved a child—an asymptomatic carrier identified incidentally. Methods: The patient underwent clinical examination, growth assessment, blood tests, hemoglobin electrophoresis, chest CT, abdominal ultrasound, echocardiography, and pulmonary perfusion scintigraphy. Whole genome sequencing (WGS) of the proband and parents was performed, followed by bioinformatic analysis and ACMG-based variant interpretation. A PRISMA-guided PubMed literature review was conducted. Results: We report on the first pediatric case exhibiting a symptomatic clinical course. A 4-year-old boy was referred for chronically low peripheral oxygen saturation (SpO₂), 78–86%, on pulse oximetry and recurrent lower respiratory tract infections. Early developmental history revealed episodes of apnea in infancy, perioral cyanosis, poor exercise tolerance, and low weight gain. Repeated cardiopulmonary assessments, chest computed tomography (CT), echocardiography, and pulmonary perfusion scintigraphy yielded unremarkable findings. Arterial blood gas analysis consistently showed normal arterial partial pressure of oxygen (PaO₂), excluding true hypoxemia. Hemoglobin electrophoresis revealed an abnormal HbD fraction; WGS identified a heterozygous variant NM_000518.5(HBB):c.112T>C inherited from the patient’s asymptomatic father. This variant increases the partial pressure of oxygen at which hemoglobin is 50% saturated (p50), thereby decreasing hemoglobin’s oxygen affinity and shifting the oxyhemoglobin dissociation curve to the right. These alterations explain the discordance between low peripheral oxygen saturation (SpO₂) and preserved oxygen delivery to tissues. Conclusions: This case expands the clinical spectrum of Hb Rothschild and demonstrates that symptomatic presentation may occur in early childhood. Awareness of low-affinity hemoglobin variants is essential to avoid misdiagnosis and unnecessary cardiopulmonary interventions. Early genetic testing facilitates accurate diagnosis and appropriate counseling. Full article

This paper presents a traffic-driven scaling framework for a digital twin proxy pool (DTPP) in vehicular edge computing (VEC), designed to eliminate the latency and synchronization issues inherent in conventional digital twin (DT) migration approaches. The core innovation lies in replacing the migration of vehicle DTs between edge servers (ESs) with instantaneous switching within a pre-allocated pool of DT proxies, thereby achieving zero migration latency and continuous synchronization. The proposed architecture differentiates between short-term DTs (SDTs) hosted in edge-side in-memory databases for real-time, low-latency services, and long-term DTs (LDTs) in the cloud for historical data aggregation. A queuing-theoretic model formulates the DTPP as an M/M/c system, deriving a closed-form lower bound for the minimum number of proxies required to satisfy a predefined queuing-delay constraint, thus transforming quality-of-service targets into analytically computable resource allocations. The scaling mechanism operates on a cloud–edge collaborative principle: a cloud-based predictor, employing a TCN-Transformer fusion model, forecasts hourly traffic arrival rates to set a baseline proxy count, while edge-side managers perform monotonic, 5 min scale-ups based on real-time monitoring to absorb sudden traffic bursts without causing service jitter. Extensive evaluations were conducted using the PeMS dataset. The TCN-Transformer predictor significantly outperforms single-model baselines, achieving a mean absolute percentage error (MAPE) of 17.83%. More importantly, dynamic scaling at the ES reduces delay violation rates substantially—for instance, from 13.57% under static provisioning to just 1.35% when the minimum proxy count is 2—confirming the system’s ability to maintain service quality under highly dynamic conditions. These findings shows that the DTPP framework provides a robust solution for resource-efficient and latency-guaranteed DT services in VEC. Full article

Parkinson’s disease (PD) is characterized by pathological changes in the substantia nigra, which in its early stages may manifest as structural and functional asymmetries between the two hemispheres. Microwave imaging has recently emerged as a promising non-invasive tool to detect subtle dielectric variations. In the context of Parkinson’s disease, such contrasts are expected to arise from the underlying physiological alterations in brain tissue, although their magnitude has not yet been fully characterized. In this work, we investigate the feasibility of differential microwave imaging, where detection is based on permittivity contrasts, through a controlled phantom study. A simple two-dimensional head phantom was constructed using a 3D-printed cylindrical container filled with water, incorporating a Teflon tube to represent the substantia nigra. The tube was filled with hot water, whose gradual cooling emulated small dielectric changes. Since the dielectric properties of water vary linearly with temperature over 0.5–3 GHz, we first validated this dependence through both numerical analysis and experimental measurements. Four antennas were then employed in a differential imaging configuration, with image reconstruction performed via the multi-frequency bi-focusing algorithm. The results show that the system can successfully detect a dielectric contrast corresponding to a temperature variation as small as 0.4 °C, equivalent to approximately 0.17% in relative permittivity. While the exact dielectric changes associated with PD remain to be determined, these results demonstrate that the proposed approach is sensitive to very small contrasts, supporting the potential of differential microwave imaging as a candidate tool for future investigations into Parkinson’s disease detection. Full article

In the realm of composite solid propellant research, the enhancement of energy performance without altering the underlying formulation holds paramount significance. This investigation employed an in situ displacement technique to establish a highly reactive interface, successfully synthesizing the [nCu+nCo+nFe]/μAl composite material, which considerably augmented the energy performance of RDX/AP. The decomposition pathways of ammonium perchlorate (AP) and RDX were optimized, resulting in a reduction in their thermal decomposition temperatures by 1.3 °C and 22.4 °C, respectively. Simultaneously, the highly reactive interface promoted efficient oxygen transport, thereby facilitating more rapid and complete reactions of aluminum. Moreover, the distinct dual-catalyst efficacy of the composite significantly enhanced the combustion efficiency of the composite energy micro-unit. Consequently, the [nCu+nCo+nFe]/μAl+RDX/AP composite energetic micro-units exhibited a notable decrease in combustion duration (from 1.58 s to 1.07 s) and elevated combustion flame temperatures (ranging from 1712.8 °C to 2205.6 °C) alongside an expanded combustion area, thus underscoring its potential for advanced propulsion applications. Full article

Background: Limited cutaneous systemic sclerosis (lcSSc) is an autoimmune disease with a wide range of different biomarkers, while inflammation-based ratios have been less extensively investigated. This study aimed to evaluate the associations between inflammation-based ratios, disease-specific parameters, and endothelial dysfunction, as well as to assess the predictive role of inflammation-based ratios in lcSSc. Methods: A total of 38 lcSSc patients and 38 matched controls with primary Raynaud’s phenomenon were analyzed at baseline regarding inflammation-based ratios, lcSSc-specific parameters, and parameters of endothelial dysfunction. LcSSc patients were prospectively observed during a 3-year follow-up period in which lcSSc complications were recorded annually. Results: LcSSc patients had a significantly higher neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio (MLR), fibrinogen-to-albumin ratio, monocyte/high-density lipoprotein (HDL) ratio, and neutrophil/HDL ratio versus controls (all p < 0.05). During follow-up, the MLR, C-reactive protein (CRP)/albumin ratio, monocyte/HDL ratio, and neutrophil/HDL ratio increased significantly (all p < 0.05) in lcSSc patients. The monocyte/HDL ratio correlated positively with the DETECT score step 2 (r = 0.453, p = 0.032) and negatively with the UCLA SCTC GIT total score (r = −0.469, p = 0.024). The CRP/albumin ratio correlated significantly with the EUSTAR index (r = 0.473, p = 0.024) and the fibrinogen-to-albumin ratio correlated with asymmetric dimethylarginine (r = 0.452, p = 0.044). The MLR and CRP/albumin ratio were associated with development of pulmonary arterial hypertension (p = 0.036, p = 0.006), and the lymphocyte/HDL ratio was associated with newly developed interstitial lung disease (p = 0.004). Conclusions: Readily available inflammation-based ratios may reflect vascular and inflammatory activity and could contribute to risk stratification for pulmonary complications in lcSSc; however, these exploratory findings require confirmation in larger cohorts. Full article

Tight sandstone gas constitutes a strategically significant resource in the exploration of unconventional hydrocarbon systems. Current understanding of the geochemical composition and genesis of tight sandstone gas in the Daning–Jixian Block, southeastern Ordos Basin, is insufficient, which hampers a comprehensive assessment of its resource potential. This study is the first to systematically investigate the geochemical characteristics and genetic origin of high-maturity tight sandstone gas in the southeastern Ordos Basin’s Daning–Jixian Block. Gas specimens were systematically acquired from multiple stratigraphic units within the reservoir interval and subjected to compositional and carbon–hydrogen isotope analysis. Compared with other gas fields in the Ordos Basin, the Daning–Jixian Block has higher average methane concentration, and notably lower ethane and propane concentrations; its average δ¹³C₁ and δ²H-CH₄ is heavier, while δ¹³C₂ and δ¹³C₃ are lighter. Based on the δ¹³C₁-δ²H-CH₄ diagram, all gas samples from the block and other basin gas fields fall into the geothermal, hydrothermal and crystalline gas domain, indicating gas genesis associated with over-mature organic matter interacting with external hydrogen. Milkov genetic diagram analysis reveals that the natural gas consists of primarily early-stage kerogen-cracking gas, with a minor contribution from crude oil-derived gas originating from Carboniferous–Permian source rocks. Notably, samples from Daning–Jixian exhibit a unique δ¹³C₁ > δ¹³C₂ reversal, attributed to mixing effects between gas from highly mature kerogen and gas from secondary cracking of crude oil. Consequently, ethane carbon isotopes alone are insufficient for definitive genetic classification. These findings provide a new geochemical interpretation framework for analogous high-maturity tight gas reservoirs. Full article

Brazil is the world’s largest coffee producer, resulting in the production of 1 kg of husk and 0.5 kg of parchment for every 1 kg of coffee beans. Given the large amount of biomass and the constant need for energy production, this study raises the possibility of using waste for pellet production. Samples of coffee husks and parchment were characterized by moisture content (dry basis), proximate analysis (volatile matter, ash and fixed carbon), calorific value, elemental analysis, and thermogravimetry, and the pellets were characterized by moisture content (dry basis), bulk density, energy density, mechanical durability, percentage of fines, and hardness. The results were compared with the ISO 17225-6. The parchment had a higher carbon, 49.5%, C/N 45.1%, and lignin 26.2% and lower ashes 2.8% and extractives 14.2%, resulting in higher calorific value, while coffee husks obtained 46.5%, 26.3%, 24.6%, 5.5%, and 34.3%, respectively. Pellets produced with parchment had a higher density 622 kg/m³ and lower moisture content 10.5%, resulting in higher energy density. The parchment pellets met all the parameters of the ISO 17225-6, while the coffee husk pellets did not meet the parameters for moisture, which is less than 15%, and bulk density, greather than 600 kg/m³. Both types of biomass showed potential for pellet production, with further studies needed on coffee husks. Full article

Bone Morphogenetic Protein-2 (BMP2) is a growth factor that maintains bone homeostasis through the BMP receptor type Ia (BMPRIa) and type II (BMPRII). BMP2 promotes osteogenesis by inducing the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts; however, it can also trigger BMSC differentiation into adipocytes. BMP2’s osteo-inductive ability has made it a potential treatment for osteoporosis, yet its dual role in BMSC differentiation complicates its efficacy. High BMP2 levels cause BMPRIa cleavage, but the downstream effects and the mechanisms governing BMP2-induced osteogenesis or adipogenesis are unresolved. Here, we identify Caspase-1 as a key mediator of BMPRIa cleavage and its downstream effects on adipogenesis. We used primary BMSCs from C57BL/6 mice, stimulated with varying BMP2 concentrations, to explore BMP2-induced BMPRIa cleavage and its impact on PPARγ—a key regulator of adipogenesis. Western blotting and immunostaining using antibodies against BMPRIa and PPARγ uncovered BMPRIa cleavage and revealed the nuclear translocation of the cleaved segment, colocalizing with PPARγ. Caspase-1 inhibition significantly reduced BMPRIa cleavage and PPARγ expression, highlighting its pivotal role in adipogenic differentiation. Understanding the molecular mechanisms of BMP2-induced adipogenesis and Caspase-1 inhibition could improve BMP2 therapeutic efficacy for osteoporosis by promoting osteogenesis over adipogenesis. Full article

Driven by the shipping industry’s pressing need to reduce its environmental impact, methanol has emerged as a promising marine fuel. Methanol-diesel dual-fuel (DF) engines present a viable solution, yet their optimization is challenging due to complex, nonlinear interactions among operational parameters. This study develops an integrated simulation and data-driven framework for multi-objective optimization of a large-bore two-stroke marine DF engine. We first establish a high-fidelity 1D model in GT-POWER, rigorously validated against experimental data with prediction errors within 10% for emissions (NOx, CO, CO₂) and 3% for performance indicators. To address computational constraints, we implement a Polynomial Regression (PR) surrogate model that accurately captures engine response characteristics. The innovative Triple-Adaptive Chaotic Sparrow Search Algorithm (TAC-SSA) serves as the core optimization tool, efficiently exploring the parameter space to generate Pareto-optimal solutions that simultaneously minimize fuel consumption and emissions. The Entropy-Weighted TOPSIS (E-TOPSIS) method then identifies the optimal compromise solution from the Pareto set. At 75% load, the framework determines an optimal configuration: methanol substitution ratio (MSR) = 93.4%; crank angle at the beginning of combustion (CAB) = 2.15 °CA; scavenge air pressure = 1.70 bar; scavenge air temperature = 26.9 °C, achieving concurrent reductions of 7.1% in NOx, 13.3% in CO, 6.1% in CO₂, and 4.1% in specific fuel oil consumption (SFOC) relative to baseline operation. Full article