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Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.

Intracerebral hemorrhage (ICH) is a devastating neurological condition that is characterized by high morbidity and long-term disability, which frequently results in severe neurological deficits. Given the limited therapeutic options, pharmacological neuroprotection has emerged as a crucial area of research. This study explored the neuroprotective potential of huperzine A (HupA) in a murine model of collagenase-induced ICH in the caudate nucleus. Three experimental groups—Sham, ICH, and ICH + HupA—were assessed at multiple timepoints (1, 3, 7, and 14 days post-ICH) for neurological function, neuroinflammatory responses, and ferroptosis-related markers. Our findings reveal that HupA exerts significant neuroprotection through dual mechanisms: (1) attenuating neuroinflammation via the suppression of IL-1β/IL-6 release and inhibition of glial activation, and (2) mitigating ferroptosis by reducing iron accumulation and upregulating glutathione peroxidase 4 (GPX4) expression, and thereby preserving neuronal viability. These results highlight the therapeutic potential of HupA in alleviating ICH-induced brain injury, and thereby offers a promising multi-target strategy for ICH treatment.

This work evaluates the influence of combining twisted fins in a triple-tube heat exchanger utilised for latent heat thermal energy storage (LHTES) in three-dimensional numerical simulation and comparing the outcome with the cases of the straight fins and no fins. The phase change material (PCM) is in the annulus between the inner and the outer tube, these tubes include a cold fluid that flows in the counter current path, to solidify the PCM and release the heat storage energy. The performance of the unit was assessed based on the liquid fraction and temperature profiles as well as solidification and the energy storage rate. This study aims to find suitable and efficient fins number and the optimum values of the Re and the inlet temperature of the heat transfer fluid. The outcomes stated the benefits of using twisted fins related to those cases of straight fins and the no-fins. The impact of multi-twisted fins was also considered to detect their influences on the solidification process. The outcomes reveal that the operation of four twisted fins decreased the solidification time by 12.7% and 22.9% compared with four straight fins and the no-fins cases, respectively. Four twisted fins improved the discharging rate by 12.4% and 22.8% compared with the cases of four straight fins and no-fins, respectively. Besides, by reducing the fins’ number from six to four and two, the solidification time reduces by 11.9% and 25.6%, respectively. The current work shows the impacts of innovative designs of fins in the LHTES to produce novel inventions for commercialisation, besides saving the power grid.

Toll-Like Receptor 9 (TLR9) elicits cellular response to nucleic acids derived from pathogens or dead cells. Previous studies have shown that TLR9-driven response may lead to differential impact on the pathogenesis of liver diseases. This study aimed to determine how TLR9 may contribute to chronic alcohol exposure-induced liver pathogenesis. We observed that TLR9 KO mice were more susceptible to alcohol-induced liver injury, which was evidenced by higher serum ALT/AST levels and more lipid accumulation in alcohol-fed TLR9 KO mice than wild-type mice. Alcohol-induced oxidative stress and mitochondrial dysfunction were also exacerbated by TLR9 KO. We found that chronic alcohol exposure-induced hepatic CHOP and ATF6 activation were enhanced in TLR9 KO mice. By using primary hepatocytes and AML-12 cells, we confirmed that TLR9 activation by CpG ODN administration significantly ameliorated acetaldehyde-induced cell injury via suppressing ATF6-CHOP signaling. By using STAT3 knockdown AML12 cells, we showed that TLR9-mediated STAT3 activation inhibited ATF6-CHOP signaling cascade and thereby protecting against acetaldehyde-induced mitochondrial dysfunction and cell injury. Interestingly, we found that TLR9 KO mice ameliorate chronic alcohol exposure-induced CXCL1 induction and neutrophils infiltration in the liver. Furthermore, hepatocyte lack of STAT3 significantly ameliorated CpG ODN and LPS-increased CXCL1 levels in hepatocytes. Overall, our data demonstrate that TLR9 signaling in hepatocytes counteracts alcohol-induced hepatotoxicity but worsens proinflammatory response.

Excessive fatty acid release from the white adipose tissue (WAT) contributes to the development of alcoholic liver disease (ALD). Lipin1 (LPIN1), as a co-regulator of DNA-bound transcription factors and a phosphatidic acid (PA) phosphatase (PAP) enzyme that dephosphorylates PA to form diacylglycerol (DAG), is dramatically reduced by alcohol in the WAT. This study aimed at determining the role of adipose LPIN1 in alcohol-induced lipodystrophy and the development of ALD. Transgenic mice overexpressing LPIN1 in adipose tissue (LPIN1-Tg) and wild type (WT) mice were fed a Lieber-DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks. Alcohol feeding to WT mice resulted in significant liver damage, which was significantly alleviated in the LPIN1-Tg mice. Alcohol feeding significantly reduced epididymal WAT (EWAT) mass, inhibited lipogenesis, and increased lipolysis in WT mice, which were attenuated in the LPIN1-Tg mice. LPIN1 overexpression also partially reversed alcohol-reduced plasma leptin levels. In WT mice, alcohol feeding induced hepatic lipid accumulation and down-regulation of beta-oxidation genes, which were dramatically alleviated in the LPIN1-Tg mice. LPIN1 overexpression also significantly attenuated alcohol-induced hepatic ER stress. These results suggest that overexpression of LPIN1 in adipose tissue restores WAT lipid storage function and secretive function to alleviate alcohol-induced liver injury.

The hepatoprotective effect of interleukin 22 (IL-22) has been reported in several models of liver injuries, including alcohol-associated liver disease (ALD). However, the intestinal role of IL-22 in alcoholic hepatitis remains to be elucidated. Intestinal IL-22 levels were measured in mice fed with alcohol for 8 weeks. IL-22 was then administered to alcohol-fed mice to test its protective effects on alleviating alcoholic hepatitis, focusing on intestinal protection. Acute IL-22 treatment was conducted in mice to further explore the link between IL-22 and the induction of antimicrobial peptide (AMP). Intestinal epithelial cell-specific knockout of signal transducer and activator of transcription 3 (STAT3) mice were generated and used for organoid study to explore its role in IL-22-mediated AMP expression and gut barrier integrity. After alcohol feeding for 8 weeks, the intestinal levels of IL-22 were significantly reduced in mice. IL-22 treatment to alcohol-fed mice mitigated liver injury as indicated by normalized serum transaminase levels, improved liver histology, reduced lipid accumulation, and attenuated inflammation. In the intestine, alcohol-reduced Reg3γ and α-defensins levels were reversed by IL-22 treatment. IL-22 also improved gut barrier integrity and decreased endotoxemia in alcohol-fed mice. While alcohol feeding significantly reduced , IL-22 administration dramatically expanded this commensal bacterium in mice. Regardless of alcohol, acute IL-22 treatment induced a fast and robust induction of intestinal AMPs and STAT3 activation. By using cultured intestinal organoids isolated from WT mice and mice deficient in intestinal epithelial-STAT3, we further demonstrated that STAT3 is required for IL-22-mediated AMP expression. In addition, IL-22 also regulates intestinal epithelium differentiation as indicated by direct regulation of sodium-hydrogen exchanger 3 via STAT3. Our study suggests that IL-22 not only targets the liver but also benefits the intestine in many aspects. The intestinal effects of IL-22 include regulating AMP expression, microbiota, and gut barrier function that is pivotal in ameliorating alcohol induced translocation of gut-derived bacterial pathogens and liver inflammation.

This study focuses on a risk assessment method for oil and gas pipelines. Oil and gas pipelines are usually constructed in a complex geological environment and are potentially dangerous. Risk assessment is a key step for their safety management. Therefore, the present paper establishes a risk indicator system as the risk assessment foundation, and we propose a risk assessment method to obtain a quantitative assessment result for the pipeline based on set pair analysis (SPA) theory. For the weight values of each indicator in the assessment process, this paper presents a calculation method based on vague sets theory. Then, a pipeline in the Yanchang oilfield was taken as a case study to verify the feasibility of the method, and the final assessment result was 2.911, which meant the pipeline was relatively safe. The method could also obtain the risk level of each indicator, showing that geological conditions, extreme weather, and public safety awareness were particularly unsafe, and service time, pipeline deformation, ground activity, and operation training were relatively unsafe. It is expected that the risk assessment result could provide a reference for pipeline safety management.

Clinical studies have demonstrated that alcoholics have a lower dietary zinc intake compared to health controls. The present study was undertaken to determine the interaction between dietary zinc deficiency and ethanol consumption in the pathogenesis of alcoholic liver disease. C57BL/6N mice were subjected to 8-week feeding of 4 experimental liquid diets: (1) zinc adequate diet, (2) zinc adequate diet plus ethanol, (3) zinc deficient diet, and (4) zinc deficient diet plus ethanol. Ethanol exposure with adequate dietary zinc resulted in liver damage as indicated by elevated plasma alanine aminotransferase level and increased hepatic lipid accumulation and inflammatory cell infiltration. Dietary zinc deficiency alone increased hepatic lipid contents, but did not induce hepatic inflammation. Dietary zinc deficiency showed synergistic effects on ethanol-induced liver damage. Dietary zinc deficiency exaggerated ethanol effects on hepatic genes related to lipid metabolism and inflammatory response. Dietary zinc deficiency worsened ethanol-induced imbalance between hepatic pro-oxidant and antioxidant enzymes and hepatic expression of cell death receptors. Dietary zinc deficiency exaggerated ethanol-induced reduction of plasma leptin, although it did not affect ethanol-induced reduction of white adipose tissue mass. Dietary zinc deficiency also deteriorated ethanol-induced gut permeability increase and plasma endotoxin elevation. These results demonstrate, for the first time, that dietary zinc deficiency is a risk factor in alcoholic liver disease, and multiple intrahepatic and extrahepatic factors may mediate the detrimental effects of zinc deficiency.

The water resource carrying capacity (WRCC) system comprises multiple complex and non-linear interactions related to society, economy, water resources, and the water environment. A comprehensive comprehension of its internal mechanisms is essential for the continual enhancement of the regional WRCC. This study concentrates on the temporal and spatial variability of the WRCC to investigate a method for dynamic successive assessment. Firstly, the pressure–state–response (PSR) framework is used to develop a systematic and causal indicator system. Then, the variable fuzzy pattern recognition (VFPR) model and an analytic hierarchy process—entropy (AHP-E) model are combined to successively and dynamically assess WRCC. The proposed method is applied to the dynamic successive assessment of WRCC in Hebei Province, and it is obtained that the poor water resource carrying capacity in Hebei Province is mainly due to the basic attribute of the decision on the water resource shortage, but Hebei Province actively adopts a variety of measures to save water and pressurize mining, which has made the province’s water resource carrying capacity tend to become better gradually. Simultaneously, a system dynamics model (SD) for water resource carrying capacity was established based on an analysis of the model structure. Moreover, three scenarios were designed, including existing continuation, high-efficiency water saving, and cross-regional water transfer. Subsequently, each scenario is further categorized into high- and low-speed economic development and population growth schemes. Afterward, simulations and predictions were conducted for a total of six schemes spanning from 2023 to 2030. The results indicate that if the current development model is adopted, the water resource carrying capacity will continue to maintain low levels. It was concluded that the high-speed development of the economy and population, the efficient water conservation, and the interbasin transfer scenario (scenario 2 with high speed) are the best choices for the sustainable development of water resources and social economy in Hebei.

Alcohol-related liver disease (ALD) is characterized by accumulation of hepatic free fatty acids (FFAs) and liver injury. The present study aimed to investigate if mechanistic target of rapamycin complex 1 (mTORC1) plays a role in FFA-induced organelle dysfunction, thereby contributing to the development of ALD. Cell studies were conducted to define the causal role and underlying mechanism of FFA-activated mTORC1 signaling in hepatocellular cell injury. C57BL/6J wild-type mice were subjected to chronic alcohol feeding with or without rapamycin to inhibit mTORC1 activation. We revealed that palmitic acid (PA)-induced ER stress and suppression of LAMP2 and autophagy flux were mTORC1-dependent as rapamycin reversed such deleterious effects. C/EBP homologous protein (CHOP) was downstream of ATF4 which partially modulated LAMP2. Supplementation with rapamycin to alcohol-fed mice attenuated mTORC1 activation and ER stress, restored LAMP2 protein, and improved autophagy, leading to amelioration of alcohol-induced liver injury. Induction of mTORC1 signaling and CHOP were also detected in the liver of patients with severe alcoholic hepatitis. This study demonstrates that hepatic FFAs play a crucial role in the pathogenesis of ALD by activating mTORC1 signaling, thereby inducing ER stress and suppressing LAMP2-autophagy flux pathway, which represents an important mechanism of FFA-induced hepatocellular injury.