Search Results (497)

Radiant tube burners (RTBs) are widely used in industrial heat-treatment furnaces, yet the coupled effects of hydrogen co-firing and exhaust gas recirculation (EGR) on their thermal fields remain insufficiently understood. This study presents a three-dimensional CFD analysis of 28 operating conditions, spanning hydrogen fractions from 0 to 100% and EGR rates from 0 to 20% at a fixed excess air ratio of 10%. The model employs the eddy dissipation concept with a reduced two-step methane mechanism, detailed hydrogen kinetics, and a Discrete Ordinates radiation model with a weighted-sum-of-gray-gases approach. All cases exhibit splitting flames: hydrogen enrichment intrinsically raises the laminar flame speed above the flame morphological transition threshold, while in pure methane, radiative preheating increases the flame speed by 29%, eliminating the triangular flame mode. The volumetric temperature uniformity index peaks near 30% H₂, whereas EGR improves uniformity in hydrogen-rich cases but slightly degrades it in methane-rich conditions. Surface temperature uniformity is maximized at 20% EGR due to near-wall thermal blanketing. Thermal efficiency increases with hydrogen fraction, from 59.1% at 0% H₂ without EGR to 68.6% at 100% H₂ with 10% EGR, while higher EGR suppresses peak temperatures. These findings provide guidance for balancing energy efficiency and temperature uniformity in hydrogen-ready RTBs. Full article

This study reports the first synthesis and full spectroscopic characterization (FT-IR, ¹H NMR, ¹³C NMR) of a novel benzoylthiourea-based compound 2-chloro-N-((2-hydroxy-4-nitrophenyl)carbamothioyl)benzamide (HNCB) and evaluates its behavior as a combustion-modifying additive in diesel–ethanol blends. Blends containing 50, 100, and 200 ppm HNCB were tested in a single-cylinder direct-injection compression ignition engine at five torque levels (0–24 Nm) and four Exhaust gas recirculation rates (0–30%) to assess combustion, performance, and emissions. Ethanol improved mixture formation and combustion stability, while HNCB, particularly at 100 ppm, provided the most favorable overall balance of combustion phasing, heat-release characteristics, and emission control. At 24 Nm and 0% exhaust gas recirculation, Diesel + Ethanol + HNCB (100 ppm) increased maximum cylinder pressure by 4.1% relative to diesel and reduced cyclic indicated mean effective pressure variability. The 50 ppm blend yielded the lowest specific fuel consumption, with reductions of up to 37% at partial loads and the highest brake thermal efficiency values under several exhaust gas recirculation conditions. Nitrogen oxides emissions decreased by up to 65–75%, whereas the 200 ppm blend increased hydrocarbon and soot at 30% exhaust gas recirculation. Overall, HNCB acted as an effective combustion modifier under the tested conditions. Full article

Background: MEIS proteins are essential homeobox transcription factors that play critical roles in development and have been increasingly implicated in oncogenesis, including breast cancer. Methods: In this study, we identified and characterized novel small-molecule MEIS2 inhibitors through in silico docking targeting the active region of the human MEIS2 homeobox domain. Lead candidates MEISi-2E, MEISi-3, and MEISi-4 were identified with binding energies ranging from −3.0 to −3.90 kcal/mol. The inhibitory potential of these molecules was validated in vitro using a species-conserved MEIS-Luciferase Reporter construct containing the TGACAG targeted locus. Results: Our results demonstrate that MEISi-2E, MEISi-3, and MEISi-4 significantly suppress MEIS-driven luciferase activity and downregulate the expression of Meis1, Meis2, and downstream genes such as IL17RB, CDH1, EGR2, PAX6, and SERPINE1 while upregulating negative regulator TGIF1 and SOX3. In breast cancer cell lines, these inhibitors exhibited potent growth inhibition, with MEISi-3 showing an exceptional IC50 as low as 0.1 μM in SK-BR-3 cells. Mechanistic studies using flow cytometry revealed that these inhibitors induce dose-dependent apoptosis and necrosis. Importantly, the novel inhibitors showed minimal toxicity to healthy human dermal and MRC5 fibroblasts, suggesting a favorable safety profile. Conclusions: These findings establish these small molecules as promising therapeutic candidates for targeting MEIS2-dependent pathways in breast cancer. Full article

Growing evidence suggests an important pathogenetic role of brain-specific gangliosides in the mechanisms underlying Alzheimer’s disease (AD), the most common form of dementia. Nutritional strategies targeting ganglioside sialylation—for example, through agglutinin-mediated modulation—have therefore attracted increasing research interest. In particular, wheat malt extract (WME), a food-derived source of wheat germ agglutinin (WGA) with high affinity for gangliosides, may influence molecular pathways involved in AD pathogenesis. Twelve-month-old female APPswe/PS1E9 transgenic mice, a model of AD, and wild-type (WT) littermates received WME or tap water for three weeks. Behavioral performance was subsequently assessed. Amyloid plaque burden and astrocyte activation were evaluated using Congo red staining and GFAP immunoreactivity, respectively. Gene expression of selected AD markers in the brain was quantified by RT–qPCR. Aged WT mice exhibited robust, region-specific molecular responses to WME, including upregulation of activity-dependent and synaptic plasticity genes (Arc, Egr1, Bdnf, Syp), enhancement of metabolic and insulin-related signaling (Pgc1a, Sirt1, Igf1r, Irs2), increased Cldn5 expression, and reduced pro-inflammatory Il1β expression. APP/PS1 mice exhibited limited response to WME, suggesting more persistent transcriptional signatures of synaptic impairment, metabolic dysregulation, and neuroinflammation than in WT mice. We found no significant effects of WME treatment on amyloid plaque density and behavior in APP/PS1 mice. No effects on astrocyte activation were observed in either group. These findings demonstrate that dietary WME counteracts abnormal behaviors and molecular changes in neuron plasticity, metabolic, and vascular markers under conditions of normal aging but fails to improve the hallmarks of AD pathology. This highlights the potential of WGA-containing nutrients as a preventive nutritional approach targeting pathogenic mechanisms of aging and, potentially, AD pathology. Full article

Injecting CO₂ into gas reservoirs is a crucial approach for enhancing natural gas recovery and achieving CO₂ geological storage, where the gas–gas diffusion behavior between CO₂ and CH₄ directly influences gas mixing efficiency. Direct observation of the spatiotemporal evolution of concentration fields during diffusion remains insufficient. In this study, a gas–gas diffusion experimental system capable of multi-time and multi-space stratified sampling within a high-temperature high-pressure PVT cell was established based on real reservoir fluid compositions. Non-equilibrium diffusion experiments were conducted under different pressures, different initial CO₂ mole fractions, and different diffusion times. A diffusion model was developed according to Fick’s second law. The results suggest that the gas column can be divided into a natural gas zone, a transition zone, and a CO₂ zone by the dimensionless concentration gradient threshold. At 5 MPa, the transition zone width expands rapidly within the first 4 h (dimensionless width increases from 0 to 0.6902), after which growth slows. Increasing pressure significantly inhibits diffusion, reducing transition zone width and prolonging equilibration time. Rising initial CO₂ concentration also suppresses diffusion mixing, particularly in the later stage. Component profile analysis confirms that, under high pressures and high CO₂ concentrations, the diffusion flux across the interface is weakened. Compared to CH₄, the diffusion equilibration time of CO₂ is shorter and more sensitive to pressure changes. The obtained diffusion coefficients (CH₄: 2.92 × 10⁻⁸ to 4.79 × 10⁻⁸ m²/s; CO₂: 3.91 × 10⁻⁸ to 6.08 × 10⁻⁸ m²/s) are on the order of 10⁻⁸ m²/s, consistent with bulk-phase PVT literature data, validating the reliability of the experimental method and inversion model. This study lays an experimental foundation for predicting multi-component gas mass transfer under conditions of CO₂-enhanced gas recovery and CO₂ geological storage. Full article

Dimethyl ether (DME) is a promising alternative fuel for compression ignition (CI) engines due to its potential to simultaneously reduce nitrogen oxides (NO_x) and particulate matter (PM) emissions while maintaining diesel-equivalent power. However, its combustion behavior under varying injection timing and exhaust gas recirculation (EGR) conditions remains insufficiently characterized for practical calibration. This study investigates the combustion, emissions, and performance of DME relative to diesel using a fully instrumented John Deere 6068CI550 single-cylinder research engine modified for high-pressure common-rail DME operation. Baseline tests were conducted at three ISO 8178 C1 steady-state modes with matched combustion phasing, load, and EGR to isolate fuel property effects. Injection timing and EGR sweeps were then performed at 1600 rpm and 50% load. Results show that DME produces 10–35% lower NO_x and orders-of-magnitude lower PM than diesel while maintaining comparable thermal efficiency. DME exhibits a single-stage premixed heat release structure with reduced peak apparent heat release rates and 4–5° shorter combustion durations than diesel. Stable combustion was sustained up to 55% EGR, beyond which incomplete combustion increased carbon monoxide (CO), total hydrocarbons (THC), and fuel consumption. Optimal low-emission operation occurred near CA50 ≈ 16° ATDC and EGR levels of 30–40%. These findings demonstrate DME’s ability to mitigate the traditional diesel NO_x–PM tradeoff and support its viability as a low-emission CI fuel. Full article

Epilepsy is mainly characterized by spontaneous seizures caused by hyperactive neural circuits. To delineate the cell-type-specific mechanisms underlying neuronal hyperexcitability, we resolve the hyperexcitability of excitatory neurons across epileptic human brain trans-foci at single-cell resolution to identify the key drivers and potential diagnostic signatures. We constructed a comprehensive atlas encompassing 240,000 cells derived from the temporal cortex and hippocampus, detecting trans-regional cellular and molecular diversity. We further delineated dynamic trajectories, gene expression patterns, and functional reorganization across cell types. Using the LASSO and random forest algorithms, we prioritized the core genes and developed a logistic regression-based diagnostic model. Despite transregional cellular landscape conservation, major cell types varied in abundance. Detailed analysis delineated various excitatory neuron subtypes’ dynamic trajectories, intricate expression, and functional reorganization, with pronounced dysfunction in the posterior hippocampal and temporal cortex networks, indicating hyperactive pro-epileptic effects. Excitatory neurons exhibit an intrinsic ability to autonomously organize themselves into distinct, highly active modules, characterized by a high activation state during epileptogenesis, as illustrated by ten epilepsy-associated functions. Transcription circuits FOSL2/FOS/EGR3/EGR1 promote neuronal hyperexcitability. Integrating epilepsy bulk RNA-seq data, we identified 24 overlapping genes between differential genes and circuit targets. The LASSO and random forest algorithms prioritized three core genes (IL1B, SOCS6, and COL4A1). A logistic regression model based on these three genes showed variable performance, with an apparent AUC of 1.000 in the discovery cohort (GSE256068) and AUCs of 0.974 and 0.722 in and two validation cohorts, indicating the need for further validation. Our study establishes the FOSL2/FOS/EGR3/EGR1 circuit as a master regulator of pathological neuronal hyperactivity across epileptic foci, linking transcriptional activation to network dysfunction. Identifying overactive factors may represent a candidate molecular pathway for future therapeutic exploration against hyperexcitability. Full article

Prenatal exposure to ionizing radiation is a known risk factor for neurodevelopmental deficits; however, the molecular mechanisms linking chronic embryonic insult to abnormal brain development remain poorly understood. This study investigated the long-term consequences of chronic prenatal gamma irradiation throughout gestation in C57BL/6 mice. Behavioural analysis of adult offspring revealed a specific increase in depression-like behaviours, with no significant alterations in anxiety or general exploratory activity. Immunohistochemical assessment demonstrated a significant reduction in adult hippocampal neurogenesis, marked by decreased doublecortin (DCX)-positive newborn neurons in the subgranular zone and fewer NeuN-positive mature neurons in the dentate gyrus hilus. Integrated RNA-seq, qPCR, and Western blot analyses implicated the upregulation of the Mef2c/Egr1 signalling pathway in this neurogenic deficit. Furthermore, miRNA sequencing identified a pronounced decrease in miR-1843a-3p, which was subsequently validated to directly target Mef2c. Collectively, these findings suggest that prenatal gamma irradiation disrupts neurogenic processes and adult brain function, leading to specific behavioral abnormalities. This long-term impairment is associated with, and may be at least partially mediated by, dysregulation of the miR-1843a-3p/Mef2c/Egr1 pathway. Full article

The APOE4 allele represents the strongest genetic risk factor for late-onset Alzheimer’s disease (AD), yet its influence on early cellular programs remains poorly understood. In this study, we investigated transcriptional differences between human induced pluripotent stem cells (iPSCs) carrying the APOE3 or APOE4 genotype. RNA sequencing revealed pronounced genotype-dependent transcriptional changes, with enrichment of genes associated with neural development and metallothioneins in APOE4 cells, while genes related to extracellular matrix organization and cell adhesion were downregulated. Protein–protein interaction network analysis confirmed the presence of clusters linked to neurodevelopmental processes and cellular stress responses in APOE4 cells. Increased expression and nuclear localization of the early neural marker SOX1 further suggest a shift towards early neural lineage commitment in APOE4 cells. In addition, altered expression of early growth response (EGR) transcription factors and reduced TNFR2 protein levels indicated genotype-specific differences in stress and inflammatory signaling pathways. Together, these findings suggest that APOE genotype-dependent alterations in transcriptional regulation, stress responses, and inflammatory signaling may already emerge in pluripotent cells and potentially influence early differentiation programs. Full article

This study evaluates the corrosion evolution of N80 steel in H₂S/CO₂ environments simulating Carbon Capture, Utilization, and Storage-Enhanced Gas Recovery (CCUS-EGR) processes. High-pressure autoclave experiments were conducted to analyze the impacts of CO₂/H₂S partial pressure ratios (2.9–67.4), temperature (40–80 °C), and flow rate. Grey relational analysis indicates that the CO₂/H₂S partial pressure ratio dominates uniform corrosion (γ = 0.880), while flow rate and temperature primarily govern pitting behavior (γ > 0.85). Increasing the ratio from 2.9 (H₂S-dominated) to 67.4 (CO₂-dominated) doubled the uniform corrosion rate to 1.042 mm/y but reduced pitting by 46%. Mechanistically, the semiconductor conductivity of FeS (∼10⁻¹ S/cm) drives deep pitting via “large cathode–small anode” galvanic effects. Additionally, fluid shear stress selectively erodes porous FeCO₃, enriching surface FeS and creating differential corrosion patterns. A comprehensive evolution model describing the transition from a H₂S-dominated regime to mixed control and finally to a CO₂-dominated regime is established, providing a theoretical foundation for wellbore integrity management throughout the CCUS-EGR lifecycle. Full article

Background: Tumor-associated macrophages (TAMs) are key components of the hepatocellular carcinoma (HCC) microenvironment, but their spatial heterogeneity remains incompletely characterized. We aimed to assess the biological and prognostic relevance of a BAG3-associated TAM program in HCC. Methods: Public single-cell RNA sequencing (scRNA-seq) datasets were analyzed to characterize TAM heterogeneity, and an integrated validation scRNA-seq dataset was used to assess reproducibility. Spatial transcriptomics was used to provide spatial context in a small treatment-exposed cohort. Pseudotime, regulatory network, and cell–cell communication analyses were performed to characterize state transitions and microenvironmental interactions. Survival modeling evaluated the prognostic relevance of the BAG3-associated program. Results: Five TAM subsets were identified, including MARCO⁺, MT⁺ RTM−, MMP9⁺, UBE2C⁺, and BAG3⁺ TAMs. Among them, BAG3⁺ TAMs, a less well-characterized subset, exhibited coordinated stress-adaptive, proteostasis-related, and matrix-remodeling programs that were reproduced in the validation dataset. Pseudotime analysis suggested a continuum of TAM states, with BAG3⁺ TAM stress-remodeling features enriched toward late pseudotime. Communication analysis centered on BAG3⁺ TAMs suggested crosstalk between inflammatory stress cues and angiogenic, stromal-remodeling, and immunomodulatory programs; this pattern was primarily supported by HBV-derived samples and recurrently involved the MIF–CD74 axis. Spatial mapping further supported BAG3⁺ TAM-enriched niches with elevated AP-1, EGR1, and NFKB1 activity. A BAG3-associated risk score derived from a 10-gene signature remained an independent prognostic factor for overall survival after clinical adjustment. Conclusions: These findings characterize a BAG3-associated TAM program with spatial, immunoregulatory, and prognostic relevance in HCC, and support its further evaluation in biomarker and mechanistic studies. Full article

Peripheral nerve ischemia–reperfusion injury is considered to contribute to sensory disturbances that impair quality of life in patients with diabetic neuropathy and chemotherapy-induced neuropathy. However, the spinal mechanisms underlying these disturbances remain unclear, partly due to the lack of established animal models and evaluation systems. In the present study, we used a rat hindlimb ischemia–reperfusion model and in vivo extracellular recording to examine bidirectional changes in neuronal activity in the spinal dorsal horn. Ischemia was induced by tightly binding the rat ankle with a rubber band, followed by reperfusion. Behavioral analysis showed a significant increase in hindlimb licking behavior after reperfusion, indicating the development of sensory disturbance-like responses. Extracellular recordings from superficial dorsal horn neurons showed diverse patterns of spontaneous firing and responses to mechanical stimulation, with both hypersensitive and desensitized responses. Furthermore, mRNA expression levels of immediate early genes (Egr1, Egr3, and Fos) were upregulated in the spinal cord after reperfusion. These results suggest that this ischemia–reperfusion model reproduces complex neuronal responses relevant to peripheral neuropathy and provides a useful evaluation system for evaluating both increased and decreased neural activity. This approach may contribute to elucidating the mechanisms of sensory disturbances and to the development of new treatments for neuropathic conditions. Full article

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by a progressive clinical course and associated with a wide range of gene transcription signatures. This review examined studies retrieved from PubMed (published between 2005 and 2025) that investigated transcription factors (TFs) correlated with SCZ. Approximately 150 studies aligning with the eligibility criteria were selected. The synthesized evidence identified more than 40 TFs implicated in the pathogenesis and risk of SCZ. Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR). The discussion shed light on how these TFs in consort with hundreds of potential genes could shape the pathophysiology of SCZ. Indeed, SCZ represents a complex genomic, nuclear, metabolic, and immune disorder characterized by a diseased cellular microenvironment, with hypoxia emerging as a key feature. Although targeting TFs pharmacologically remains challenging, innovative therapeutic strategies—such as antineoplastic and antipsychotic agents that modulate the cellular microenvironment—may offer promising new directions for SCZ treatment. Full article

Addressing the problem of limited methane (CH₄) recovery degree under different production conditions in a target low-permeability carbonate gas reservoir, this study intends to further investigate the effect of carbon dioxide (CO₂) injection on enhanced gas recovery (EGR). A group of long-core physical simulation experiments of CO₂ injection for EGR was adopted. Field injection–production parameters were converted to laboratory conditions through similarity criteria to simulate the actual production process of gas wells. Systematic experiments on CH₄ depletion and CO₂ displacement were carried out under different irreducible water saturation, gas injection timing pressure and injection rates. The influence laws of each key parameter on the CO₂ breakthrough time and CH₄ recovery degree were analyzed emphatically, and the optimal injection–production scheme was obtained. For the target low-permeability carbonate gas reservoir (permeability < 1 mD), the optimal CO₂ injection scheme is as follows: for layers with medium to high irreducible water saturation (≥40%), CO₂ injection at a rate of 36,000 m³/d per well after the end of stable production (formation pressure > 7.38 MPa) can increase the CH₄ recovery degree by 3–5%. This study provides experimental support for the optimization of CO₂ injection schemes for enhanced recovery in gas reservoirs and the adjustment of gas reservoir development strategies under different irreducible water saturation conditions. Full article

Internal combustion engines fueled by fossil fuels are major contributors to greenhouse gas (GHG) emissions. This study analyzes and predicts GHG emissions from hydrogen-enriched compressed natural gas (HCNG)-fueled spark-ignition (SI) engines. Experiments were conducted under stoichiometric conditions, and emissions before and after the three-way catalytic converter (TWC) were analyzed by varying hydrogen fraction (0–50%), EGR ratio (0–23%), engine speed (900 rpm–1500 rpm), engine load (25–75%), and spark timing (8–49 °CA bTDC). Before the TWC, increasing the hydrogen fraction from HCNG0% to HCNG40% at 1500 rpm, 50% load, and 23% EGR reduced total GHG emissions from 184.3 to 65.17 g/kWh. Similarly, for HCNG20% at 900 rpm and 30% load, the TWC reduced the CO₂-equivalent emissions of CO, CH₄, and NOx from 18.531, 8.149, and 9.057 g${\mathrm{C}\mathrm{O}}_{2eq}$/kWh to 7.013, 1.626, and 0.429 g${\mathrm{C}\mathrm{O}}_{2eq}$/kWh, respectively. Pearson correlation analysis revealed strong linear relationships between operating parameters and GHG emissions. Furthermore, emissions were predicted using four Gaussian process regression (GPR) models: Squared, Exponential, Matern 5/2, and Rational. Among these, the Exponential GPR demonstrated the highest predictive accuracy, achieving RMSE values of 0.098, 0.022, and 0.035, with corresponding R² values of 0.999, 0.807, and 0.996 for CO, CH₄, and NOx, respectively. The findings of this study offer valuable insights into GHG emissions and support the development of cleaner, more efficient HCNG engines. Full article