Search Results (508)

It is well-known that the morbidity and clinical burden of type 2 diabetes mellitus (T2DM) are predominantly associated with its chronic complications, in which fibrosis is a significant contributor. Recently, sodium–glucose cotransporter 2 (SGLT2) inhibitors have made a pivotal advancement in the therapeutic landscape not only improving glycemic control, but also demonstrating high effectiveness in the prevention and treatment of T2DM complications. In this work, we aimed to assess the transcription factors (TFs) mediating the effects of SGLT2 inhibitor empagliflozin (EMPA) treatment by a comprehensive analysis of the allele-specific expression (ASE) events utilizing the RNA-seq data. Initial logistic regression analysis of the in vitro transcriptomic data for EMPA-treated peripheral blood mononuclear cells (PBMCs) of three healthy donors revealed a significant inter-individual variation in ASE for 240 genes linked to EMPA treatment beyond the glucose-lowering effects. Then, 146 TFs were predicted to regulate the expression of the corresponding targets using motifbreakR and DESeq2. Among these, multiple TFs (including ATF3, ATF4, E2F1, EGR1, FOS, JUN, JUNB, IRF8, KLF6, KLF11, SNAI1, TWIST1, and ZEB1) were involved in the TGF-β/SMAD3 canonical profibrotic signaling cascade, pertinent to diabetes-related fibrosis, playing a significant role in the development of diabetic complications. Further analysis of the in vivo data for the PBMCs from ten T2DM patients initiating EMPA therapy identified 98 TFs related to the ASE variation in both in vitro and in vivo cohorts. To conclude, our integrative allele-specific approach enables the prediction of novel EMPA-responsive regulatory interactions and suggests the important mediators of the mechanisms underlying the effects of EMPA on human PBMCs. Full article

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease with a complex molecular basis. This study aims to identify key molecules involved in OA pathogenesis, focusing on the role of acetylation-related gene expression. Methods: Public microarray datasets GSE82107 and GSE169077 were integrated to construct a differential expression landscape between OA patients and healthy controls. Acetylation-linked differentially expressed genes (acetylation-DEGs, ARDEGs) were extracted by intersecting DEGs with a curated set of acetyltransferases, deacetylases and acetylation substrates. A protein–protein interaction (PPI) network was built and subjected to LASSO-penalized regression to prioritise hub genes. Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Variation Analysis (GSVA) were performed to characterize biological themes. Immune infiltration was quantified with CIBERSORTx and single-sample Gene Set Enrichment Analysis (ssGSEA). Single-cell RNA-seq data (GSE216651) were employed for orthogonal validation. For experimental corroboration, synovial tissue was collected from OA patients undergoing arthroplasty; mRNA and protein levels of hub genes were determined by qRT-PCR, Western blot and immunofluorescence. The destabilisation of the medial meniscus (DMM) mouse model was used for in vivo verification. Results: Twenty-one high-confidence ARDEGs were identified. Analysis of the PPI network yielded ten hub nodes, six of which (EGR1, PFKFB3, HDAC4, MMP13, PDK4 and ACADL) retained non-zero coefficients in the least absolute shrinkage and selection operator (LASSO) model. Enrichment analyses implicated these genes in embryonic development, collagen-containing extracellular matrix remodeling and PI3K–Akt signaling. Immune infiltration analysis showed potential differences in immune cell abundance between OA and healthy controls. Single-cell dataset analysis verified the expression patterns of key genes in different cell types. Concordant dysregulation of EGR1, PFKFB3, HDAC4, MMP13 and PDK4 was observed at both mRNA and protein levels in human OA synovium and DMM mouse joints. Conclusion: This comprehensive analysis identified acetylation-related genes and analyzed their potential biological roles in OA. The identified ARDEGs may provide new insights into OA diagnosis and treatment. Full article

Post-combustion amine absorption is the most mature CO₂ capture technology, while membrane separation is a promising alternative due to its modularity and operational simplicity. Process intensification through exhaust gas recirculation (EGR) has also gained attention for increasing flue gas CO₂ concentration and reducing capture energy demand. However, comprehensive techno-economic comparisons of absorption, membrane, and hybrid systems under EGR-integrated NGCC conditions remain limited. This study presents a techno-economic assessment of multiple CO₂ capture configurations for a 450 MW NGCC power plant. Process simulations were performed using Aspen Plus and Aspen Custom Modeler to evaluate absorption, membrane, and hybrid systems integrated with conventional and selective EGR. The analysis considers full steam cycle integration and compares energy consumption, net plant efficiency, levelized cost of electricity (LCOE), and CO₂ avoidance cost. The results show that EGR significantly improves carbon capture performance. Among all cases, selective EGR combined with amine absorption delivers the best performance, reducing the energy penalty by more than 30% compared with standalone absorption and by over 70% relative to membrane separation. This configuration achieves an LCOE of approximately 72 USD/MWh and a CO₂ avoidance cost of about 39 USD/tCO₂, outperforming the selective EGR–membrane system (77 USD/MWh and 51 USD/tCO₂). These findings demonstrate that integrating selective EGR with amine absorption is a highly promising strategy for improving the technical and economic feasibility of CCSU in NGCC power plants. Full article

Ammonia is increasingly regarded as a carbon-free energy carrier for hard-to-electrify power sectors, including marine propulsion, heavy-duty transport, and distributed generation. Its direct use in internal combustion engines, however, is constrained by high ignition energy, low laminar flame speed, narrow flammability limits, slow low-temperature chemistry, and strong trade-offs among efficiency, nitrogen-containing emissions, and unburned ammonia slip. Hydrogen enrichment is one of the most effective routes for improving ammonia combustion reactivity, but it also introduces a multivariable control problem: hydrogen fraction, ammonia injection timing, injection mode, air-path dilution, ignition strategy, and aftertreatment operation are tightly coupled and strongly condition-dependent. This review synthesizes recent progress in ammonia–hydrogen and ammonia-based dual-fuel engine control from a control-oriented perspective. The discussion first summarizes application scenarios, nonlinear combustion-mode transitions, emission-formation pathways, and control-relevant metrics. It then compares actuator-level strategies, including ammonia injection timing and staging, port and direct injection, hydrogen energy-fraction scheduling, excess-air-ratio and EGR control, high-energy ignition, and turbulent jet ignition. Advanced optimization methods are further reviewed, with emphasis on model predictive control, control-oriented combustion and emission models, artificial-intelligence-based virtual sensors, and reinforcement-learning control. The analysis shows that the central challenge is no longer whether ammonia can burn in an engine, but how a controller can keep the system inside a narrow moving window bounded by misfire, knock, NO_x, N₂O, and NH₃ slip. Finally, future research priorities are proposed, including engine–aftertreatment co-optimization, physics-informed virtual sensing, digital-twin-assisted calibration, lightweight deployment on electronic control units, and robust control under fuel and aging uncertainty. Full article

Major depressive disorder (MDD) has been linked to oxidative stress, mitochondrial dysfunction, and impaired neuronal plasticity, but the reproducibility of related transcriptomic alterations across postmortem brain cohorts remains uncertain. We performed a targeted cross-platform analysis of a prespecified 14-gene panel spanning antioxidant defense, mitochondrial-redox regulation, cellular stress responses, neurotrophic signaling, synaptic plasticity, and polyamine metabolism across seven postmortem dorsolateral prefrontal cortex cohorts comprising 146 MDD cases and 179 controls. Primary support required Fisher-combined evidence, Benjamini–Hochberg correction across the panel, and concordant MDD-minus-control direction across all available cohorts. NPTX2, EGR1, VGF, BDNF, and SAT1 met these criteria, with lower expression in MDD. The same five-gene pattern was supported by weighted signed Stouffer analysis, one-stage generalized least-squares models, random-effects meta-analysis, and 200,000 disease-label permutations; none produced at least five genes meeting the complete primary-support criterion (empirical p = 5.0 × 10⁻⁶). The most robust cross-cohort finding was a convergent lower-expression pattern across genes supporting redox-linked stress adaptation, polyamine homeostasis, neurotrophic signaling, activity-dependent transcription, and synaptic plasticity. This pattern suggests impaired molecular capacity for neuronal stress resilience and adaptive plasticity in MDD. Full article

In heterogeneous edge-water carbonate gas reservoirs during the middle-to-late development stage, edge-water invasion and pressure depletion significantly compromise production stability and gas recovery. To investigate water invasion behavior under permeability heterogeneity and evaluate the effectiveness of CO₂ injection for water control and enhanced gas recovery, a series of long-core depletion experiments and three-dimensional vertically heterogeneous physical-model experiments were conducted based on representative reservoir conditions. The results show that permeability contrast plays a key role in governing water breakthrough timing and gas production performance. High-permeability cores experience earlier water breakthrough but contribute higher overall recovery, whereas low-permeability cores exhibit delayed depletion and pronounced production decline after breakthrough due to large pressure differentials. In multilayer commingled production, interlayer pressure imbalance drives fluid crossflow from low- and medium-permeability zones toward high-permeability zones, leading to premature water breakthrough, delayed layer activation, and the development of water-blocked gas zones, thereby intensifying interlayer heterogeneity. After depletion, CO₂ injection effectively modifies fluid flow pathways and improves reservoir connectivity. Through gravity-assisted displacement and energy replenishment, CO₂ mitigates water invasion, reconnects previously isolated gas zones, and enhances overall reservoir utilization. The findings demonstrate that CO₂ injection provides a dual benefit in both water control and production enhancement, offering valuable insights for improving recovery strategies in heterogeneous edge-water gas reservoirs. Full article

The injection of CO₂ into mature natural gas reservoirs is widely recognised for its potential to store carbon dioxide while simultaneously enhancing natural gas recovery. However, across all reservoir pressure and temperature ranges, CO₂ and natural gas are miscible, leading to contamination of the produced gas and increasing surface processing costs. Although miscibility has been a limiting factor in deploying CO₂-EGR-based projects, several strategies have been proposed to mitigate it. In this study, we have analysed the inclusion of water in the CO₂ injection process to reduce mixing, improve natural displacement, and improve carbon dioxide storage security through solubility and residual trapping mechanisms. The simulation was conducted in a 3D reservoir using the CMG-GEM simulator. The results show that the inclusion of water injection improves natural gas recovery by up to 8.04% compared with when only CO₂ was injected. The CO₂ breakthrough time increased by up to 931 days, while the hysteresis and solubility trapped CO₂ were improved by 2.68% and 3.06%, respectively. EGR and CO₂ storage security were found to be affected by reservoir heterogeneity, injection rate, and the perforation depths of injector and producer wells. Full article

Background/Objectives: Liver fibrosis, a wound-healing response to chronic liver injury characterized by excessive extracellular matrix (ECM) accumulation, represents a major global health burden with no approved anti-fibrotic therapies. Pien Tze Huang (PZH), an officially approved traditional Chinese medicine (NMPA Drug Approval No. Z35020243), has demonstrated hepatoprotective effects, yet its epigenetic mechanisms in fibrosis treatment remain unexplored. Methods: We performed the first integrated methylome–transcriptome–proteome analysis to investigate PZH’s anti-fibrotic mechanisms in a CCl₄-induced mouse model using reduced representation bisulfite sequencing (RRBS), RNA-seq, and TMT-labeled LC-MS/MS. Results: We identified 10,974 differentially methylated loci (DMLs) and 773 differentially expressed genes (DEGs) modulated by PZH treatment. Integration analysis revealed ANXA3 and CORO1A as candidate therapeutic targets exhibiting significant inverse methylation-expression correlations validated at both transcriptomic and proteomic levels. Notably, PZH treatment modulated the CRLF-CLCF1 cytokine complex and the EGR-3 transcription factor network (42/44 genes enriched), suggesting broad transcriptional reprogramming in fibrotic liver. Protein–protein interaction (PPI) analysis highlighted key gene pairs such as Dnmt1-Uhrf1, Cbfb-Runx1, and Col4a1-Col4a2, implicating PZH in epigenetic maintenance, transcription factor regulation, and ECM remodeling. Conclusions: These findings suggest mechanistic insights into PZH’s multi-target anti-fibrotic effects and offer a rationale for developing potential therapeutic targets for liver fibrosis. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with limited treatment options. Here, we demonstrate that fucoxanthin (FUCO), a natural marine carotenoid, attenuates free fatty acid (FFA)-induced hepatocellular steatosis and inflammatory responses in vitro by targeting the EGR2-CD36 axis (EGR2, early growth response protein 2; CD36, cluster of differentiation 36). In FFA-induced hepatocyte models (HepG2, Hep3B, and AML12), FUCO significantly reduced lipid accumulation and inflammatory markers without cytotoxicity. Mechanistic studies revealed that FUCO specifically inhibited fatty acid uptake and transport by downregulating CD36, while triglyceride (TG) degradation remained unaffected. RNA sequencing identified EGR2 as a master regulator induced by FFA and suppressed by FUCO. Functional validation showed that EGR2 overexpression completely blocked FUCO’s lipid-lowering effects and restored CD36 expression, confirming that FUCO acts through EGR2-dependent CD36 inhibition. Bioinformatic analysis further supported EGR2-mediated regulation of CD36 via tumor necrosis factor (TNF) and sterol regulatory element-binding factor (SREBF) pathways. Collectively, our findings establish EGR2 as a critical molecular target for FUCO and provide mechanistic insights that may support its further evaluation in preclinical models for MASH therapy. Full article

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