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Recruitment of inflammatory cells is a major feature of alcoholic liver injury however; the signals and cellular sources regulating this are not well defined. C-C chemokine receptor type 2 (CCR2) is expressed by active hepatic stellate cells (HSC) and is a key monocyte recruitment signal. Activated HSC are also important sources of hydrogen peroxide resulting from the activation of NADPH oxidase 4 (NOX4). As the role of this NOX in early alcoholic liver injury has not been addressed, we studied NOX4-mediated regulation of CCR2/CCL2 mRNA stability. NOX4 mRNA was significantly induced in patients with alcoholic liver injury, and was co-localized with αSMA-expressing activated HSC. We generated HSC-specific NOX4 KO mice and these were pair-fed on alcohol diet. Lipid peroxidation have not changed significantly however, the expression of CCR2, CCL2, Ly6C, TNFα, and IL-6 was significantly reduced in NOX4 HSCKO compared to fl/fl mice. NOX4 promoter was induced in HSC by acetaldehyde treatment, and NOX4 has significantly increased mRNA half-life of CCR2 and CCL2 in conjunction with Ser221 phosphorylation and cytoplasmic shuttling of HuR. In conclusion, NOX4 is induced in early alcoholic liver injury and regulates CCR2/CCL2 mRNA stability thereby promoting recruitment of inflammatory cells and production of proinflammatory cytokines.

Type 2 diabetes is clinically associated with progressive necroinflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Advanced glycation end-products (AGEs) accumulate during prolonged hyperglycemia, but the mechanistic pathways that lead to accelerated liver fibrosis have not been well defined. In this study, we show that the AGEs clearance receptor AGER1 was downregulated in patients with NASH and diabetes and in our NASH models, whereas the proinflammatory receptor RAGE was induced. These findings were associated with necroinflammatory, fibrogenic, and pro-oxidant activity via the NADPH oxidase 4. Inhibition of AGEs or RAGE deletion in hepatocytes in vivo reversed these effects. We demonstrate that dysregulation of NRF2 by neddylation of cullin 3 was linked to AGER1 downregulation and that induction of NRF2 using an adeno-associated virus-mediated approach in hepatocytes in vivo reversed AGER1 downregulation, lowered the level of AGEs, and improved proinflammatory and fibrogenic responses in mice on a high AGEs diet. In patients with NASH and diabetes or insulin resistance, low AGER1 levels were associated with hepatocyte ballooning degeneration and ductular reaction. Collectively, prolonged exposure to AGEs in the liver promotes an AGER1/RAGE imbalance and consequent redox, inflammatory, and fibrogenic activity in NASH.

According to the experimental data and proposed kinetic model, reaction obeys a first-order-reaction kinetic.

By improving growth conditions, prolifera- tion of bacteria, analysis and identification of metabolites resulting from degradation, it can be applied in a semi- industrial pilot to attempt for clean-up the dyes and produc- ing beneficial metabolites such as acids, alcohols and other harmless substances.

Background: Streptomyces l vis is a member of Actinomycetes family. Chemical compounds extracted from this bacterium have been used as antibiotics, anti-tumoral, anti-bacterial, anti-fungal, antiviral, anticancer factors. The purpose of this study‚ was to investigate different metabolites of Streptomyces strains isolated from north west soils, of Iran and antimicrobial effects of them.Methods: The soil samples were taken from north west of Iran in 2010. The isolated bacteria were purified and identified by conventional methods. The metabolites of this bacterium were extracted by 7 different solvents (diethyl ether, dichloromethane, hexane, ethyl acetate, chloroform, methanol and water). The antimicrobial effects of metabolites were tested by disk agar diffusion method on Gram-positive and Gram- negative bacteria. The metabolites with antibacterial effects were analyzed by gas chromatography-mass spectrometry (GC-MS).Results: Metabolites produced from diethyl ether solvent affected Gram- positive and Gram- negative strains and 15 different compounds identified in the active metabolite of the bacterium. The main ingredients were: Docosanoic acid, methyl ester (11.578%), 9-12-octadecadienoic acid (2.961%), 5-Tetracosenois acid, methyl ester (8.389%), Bis (2-ethylhexyl) phthalate (2.153%), and D-alpha-Tocopherol (0.959%).Conclusion: Results of this study showed that docosanoic acid, methyl ester (11.578%) and 5-tetracosenois acid methyl ester (8.389%), were the main metabolites of Streptomyces levis isolated from north west soils of Iran. Antimicrobial effects of extracts could be due to the presence of 1, 2-benzene dicarboxylic acid diisooctyl ester compounds and bis (2-ethylhexyl) phthalate in the metabolite.

Recently, the early diagnosis of Alzheimer’s disease has gained major attention due to the growing prevalence of the disease and the resulting costs imposed on individuals and society. The main objective of this study was to propose an ensemble method based on deep learning for the early diagnosis of AD using MRI images. The methodology of this study consisted of collecting the dataset, preprocessing, creating the individual and ensemble models, evaluating the models based on ADNI data, and validating the trained model based on the local dataset. The proposed method was an ensemble approach selected through a comparative analysis of various ensemble scenarios. Finally, the six best individual CNN-based classifiers were selected to combine and constitute the ensemble model. The evaluation showed an accuracy rate of 98.57, 96.37, 94.22, 99.83, 93.88, and 93.92 for NC/AD, NC/EMCI, EMCI/LMCI, LMCI/AD, four-way and three-way classification groups, respectively. The validation results on the local dataset revealed an accuracy of 88.46 for three-way classification. Our performance results were higher than most reviewed studies and comparable with others. Although comparative analysis showed superior results of ensemble methods against individual architectures, there were no significant differences among various ensemble approaches. The validation results revealed the low performance of individual models in practice. In contrast, the ensemble method showed promising results. However, further studies on various and larger datasets are required to validate the generalizability of the model.

Low-temperature cracking is a significant concern in asphalt pavements, especially in regions exposed to moisture with varying acidity from surface runoff. This study investigated whether nano-iron oxide (Fe₂O₃) and nano-aluminum oxide (Al₂O₃) can enhance the cracking resistance of hot-mix asphalt (HMA) under such environmental stresses. PG 58–22 bitumen was modified with 0.5% and 1% of the nanomaterial by weight. The modified mixtures were evaluated using semi-circular bending (SCB) and Pull-Off tests to assess fracture energy (FE), fracture toughness (FT), cohesion (CP), and adhesion (AP). Moisture conditioning at pH levels of 5, 6, 7, 8, and 9 simulated the effects of acidic and alkaline environments. Exposure to non-neutral moisture significantly reduced the fracture, adhesive, and cohesive properties of unmodified HMA. In contrast, both nanomaterials improved performance across all parameters, with nano-Al₂O₃ demonstrating superior results compared to nano-Fe₂O₃. The nanomaterials also enhanced the m-value of bitumen, indicating improved stress relaxation capacity at low temperatures. Increasing the nanomaterial content from 0.5% to 1% led to further improvements, particularly under extreme pH conditions. Statistical analysis confirmed that aggregate type, bitumen modification, and environmental conditions significantly affected FE, FT, CP, and AP parameters. The only exception was CP, which was not significantly influenced by aggregate type. The combination of limestone aggregate and 1% nano-Al₂O₃ was identified as the most effective in mitigating low-temperature cracking. These findings suggest nano-Al₂O₃ and nano-Fe₂O₃ as promising modifiers for enhancing pavement durability, reducing moisture sensitivity, and improving the longevity of asphalt surfaces exposed to challenging environmental conditions.

Hydroplaning speed can be affected by pavement texture depth, thickness of water film, tire pressure and tread depth. In this study, to understand the influence of pavement texture on the hydroplaning speed, a new lab-scale apparatus has been designed and manufactured. The lack of proportion between linear movement of vehicle shaft and the wheel rotation was found to be a good index to determine hydroplaning threshold. A 5% drop in the ratio of wheel-to-axle rotation has been assumed as an index to determine hydroplaning threshold. Based on the measures, a simplified model was developed that is able to predict the hydroplaning speed depending on pavement’s texture characteristics. The results indicated that a 77% increase in mean texture depth cause 9% increase in hydroplaning threshold speed.

Introduction: High metastasis, resistance to common treatments, and high mortality rate, has made triple-negative breast cancer (TNBC) to be the most invasive type of breast cancer. High telomerase activity and mitochondrial biogenesis are involved in breast cancer tumorigenesis. The catalytic subunit of telomerase, telomerase reverse transcriptase (hTERT), plays a role in telomere lengthening and extra-biological functions such as gene expression, mitochondria function, and apoptosis. In this study, it has been aimed to evaluate intrinsic-, extrinsic-apoptosis and DNMT3a and TET2 expression following the inhibition of telomerase and mitochondria respiration in TNBC cell lines. Methods: TNBC cells were treated with IC50 levels of BIBR1532, tigecycline, and also their combination. Then, telomere length, and DNMT3a, TET2, and hTERT expression were evaluated. Finally, apoptosis rate, apoptosis-related proteins, and genes were analyzed. Results: The present results showed that IC50 level of telomerase and inhibition of mitochondria respiration induced apoptosis but did not leave any significant effect on telomere length. The results also indicated that telomerase inhibition induced extrinsic-apoptosis in MDA-MB-231 and caused intrinsic- apoptosis in MDA-MB-468 cells. Furthermore, it was found that the expression of p53 decreased and was ineffective in cell apoptosis. The expressions of DNMT3a and TET2 increased in cells. In addition, combination treatment was better than BIBR1532 and tigecycline alone. Conclusion: The inhibition of telomerase and mitochondria respiration caused intrinsic- and extrinsic- apoptosis and increased DNMT3a and TET2 expression and it could be utilized in breast cancer treatment.