Fructose intake is known to induce obesity, insulin resistance, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the effects of fructose drinking on gut ...leakiness, endotoxemia, and NAFLD and study the underlying mechanisms in rats, mice, and T84 colon cells. Levels of ileum junctional proteins, oxidative stress markers, and apoptosis‐related proteins in rodents, T84 colonic cells, and human ileums were determined by immunoblotting, immunoprecipitation, and immunofluorescence analyses. Fructose drinking caused microbiome change, leaky gut, and hepatic inflammation/fibrosis with increased levels of nitroxidative stress marker proteins cytochrome P450‐2E1 (CYP2E1), inducible nitric oxide synthase, and nitrated proteins in small intestine and liver of rodents. Fructose drinking significantly elevated plasma bacterial endotoxin levels, likely resulting from decreased levels of intestinal tight junction (TJ) proteins (zonula occludens 1, occludin, claudin‐1, and claudin‐4), adherent junction (AJ) proteins (β‐catenin and E‐cadherin), and desmosome plakoglobin, along with α‐tubulin, in wild‐type rodents, but not in fructose‐exposed Cyp2e1‐null mice. Consistently, decreased intestinal TJ/AJ proteins and increased hepatic inflammation with fibrosis were observed in autopsied obese people compared to lean individuals. Furthermore, histological and biochemical analyses showed markedly elevated hepatic fibrosis marker proteins in fructose‐exposed rats compared to controls. Immunoprecipitation followed by immunoblot analyses revealed that intestinal TJ proteins were nitrated and ubiquitinated, leading to their decreased levels in fructose‐exposed rats. Conclusion: These results showed that fructose intake causes protein nitration of intestinal TJ and AJ proteins, resulting in increased gut leakiness, endotoxemia, and steatohepatitis with liver fibrosis, at least partly, through a CYP2E1‐dependent manner.
As the technology of flexible electronics has remarkably advanced, the long-term reliability of flexible devices has attracted much attention, as it is an important factor for such devices in ...reaching real commercial viability. To guarantee the bending fatigue lifetime, the exact evaluation of bending strain and the change in electrical resistance is required. In this study, we investigated the bending strains of Cu thin films on flexible polyimide substrates with different thicknesses using monolayer and bilayer bending models and monitored the electrical resistance of the metal electrode during a bending fatigue test. For a thin metal electrode, the bending strain and fatigue lifetime were similar regardless of substrate thickness, but for a thick metal film, the fatigue lifetime was changed by different bending strains in the metal electrode according to substrate thickness. To obtain the exact bending strain distribution, we conducted a finite-element simulation and compared the bending strains of thin and thick metal structures. For thick metal electrodes, the real bending strain obtained from a bilayer model or simulation showed values much different from those from a simple monolayer model. This study can provide useful guidelines for developing highly reliable flexible electronics.
In this study, we explore how the strategic positioning of conductive yarns influences the performance of plated knit strain sensors fabricated using commercial knitting machines with both conductive ...and non-conductive yarns. Our study reveals that sensors with conductive yarns located at the rear, referred to as 'purl plated sensors', exhibit superior performance in comparison to those with conductive yarns at the front, or 'knit plated sensors'. Specifically, purl plated sensors demonstrate a higher sensitivity, evidenced by a gauge factor ranging from 3 to 18, and a minimized strain delay, indicated by a 1% strain in their electromechanical response. To elucidate the mechanisms behind these observations, we developed an equivalent circuit model. This model examines the role of contact resistance within varying yarn configurations on the sensors' sensitivity, highlighting the critical influence of contact resistance in conductive yarns subjected to wale-wise stretching on sensor responsiveness. Furthermore, our findings illustrate that the purl plated sensors benefit from the vertical movement of non-conductive yarns, which promotes enhanced contact between adjacent conductive yarns, thereby improving both the stability and sensitivity of the sensors. The practicality of these sensors is confirmed through bending cycle tests with an in situ monitoring system, showcasing the purl plated sensors' exceptional reproducibility, with a standard deviation of 0.015 across 1000 cycles, and their superior sensitivity, making them ideal for wearable devices designed for real-time joint movement monitoring. This research highlights the critical importance of conductive yarn placement in sensor efficacy, providing valuable guidance for crafting advanced textile-based strain sensors.
Mitochondrial translocation of pro-apoptotic Bax prior to apoptosis is well established after treatment with many cell death stimulants or under apoptosis-inducing conditions. The mechanism of ...mitochondrial translocation of Bax is, however, still unknown. The aim of this work was to investigate the mechanism of Bax activation and mitochondrial translocation to initiate apoptosis of human hepatoma HepG2 and porcine kidney LLC-PK1 cells exposed to various cell death agonists. Phosphorylation of Bax by JNK and p38 kinase activated after treatment with staurosporine, H2O2, etoposide, and UV light was demonstrated by the shift in the pI value of Bax on two-dimensional gels and confirmed by metabolic labeling with inorganic 32Pphosphate in HepG2 cells. Specific inhibitors of JNK and p38 kinase significantly inhibited Bax phosphorylation and mitochondrial translocation and apoptosis of HepG2 cells. A specific small interfering RNA to MAPKK4 (the upstream protein kinase of JNK and p38 kinase) markedly decreased the levels of MAPKK4 and MAPKK3/6, blocked the activation of JNK or p38 kinase, and inhibited Bax phosphorylation. However, the negative control small interfering RNA did not cause these changes. Confocal microscopy of various Bax mutants showed differential rates of mitochondrial translocation of Bax before and after staurosporine treatment. Among the Bax mutants, T167D did not translocate to mitochondria after staurosporine exposure, suggesting that Thr167 is a potential phosphorylation site. In conclusion, our results demonstrate, for the first time, that Bax is phosphorylated by stress-activated JNK and/or p38 kinase and that phosphorylation of Bax leads to mitochondrial translocation prior to apoptosis.
Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other ...conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C p.Glu373Ala) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T p.Cys268Phe) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.
•Hepatic inflammation is one of the most distinguishing features of NASH.•miR-451 expression was down-regulated in the inflammatory progression of NAFLD.•Downregulation of miR-451 mediates the ...hepatic inflammation.•miR-451 over-expression suppresses PA-induced proinflammatory cytokine production in steatotic cells.•miR-451 expression inhibits PA- induced NF-κB activation in steatotic cells.
Mechanisms associated with the progression of non-alcoholic fatty liver disease (NAFLD) remain unclear. We attempted to identify the pattern of altered gene expression at different time points in a high fat diet (HFD)-induced NAFLD mouse model. The early up-regulated genes are mainly involved in the innate immune responses, while the late up-regulated genes represent the inflammation processes. Although recent studies have shown that microRNAs play important roles in hepatic metabolic functions, the pivotal role of microRNAs in the progression of NAFLD is not fully understood. We investigated the functions of miR-451, which was identified as a target gene in the inflammatory process in NAFLD. miR-451 expression was significantly decreased in the palmitate (PA)-exposed HepG2 cells and in liver tissues of HFD-induced non-alcoholic steatohepatitis (NASH) mice. Its decreased expressions were also observed in liver specimens of NASH patients. In vitro analysis of the effect of miR-451 on proinflammatory cytokine provided evidence for negative regulation of PA-induced interleukin (IL)-8 and tumor necrosis factor-alpha (TNF-α) production. Furthermore, miR-451 over-expression inhibited translocation of the PA-induced NF-κB p65 subunit into the nucleus. Our result showed that Cab39 is a direct target of miRNA-451 in steatotic cells. Further study showed that AMPK activated through Cab39 inhibits NF-κB transactivation induced in steatotic HepG2 cells. miR-451 over-expression in steatotic cells significantly suppressed PA-induced inflammatory cytokine. These results provide new insights into the negative regulation of miR-451 in fatty acid-induced inflammation via the AMPK/AKT pathway and demonstrate potential therapeutic applications for miR-451 in preventing the progression from simple steatosis to severely advanced liver disease.
We report the case of a patient who developed extensive brain lesions during fingolimod (FTY720) treatment in the TRANSFORMS study. His initial diagnosis was multiple sclerosis, but after ...encephalopathy anti-aquaporin4 antibody (anti-AQP4 Ab) was detected, it was changed to neuromyelitis optica spectrum disorder. After treatment with fingolimod, he developed bilateral extensive brain lesions. The brain MRI showed lesions predominantly involving the right frontal and parietal lobes, with vasogenic edema and enhancement. He had residual encephalomalacia and no recurrence with steroid treatment over 3 years following withdrawal of fingolimod.
Silver nanowires (AgNWs) based conductive electrode have shown potential for use in large area flexible optoelectronic applications. Presently, considerable efforts are being made to lower the ...surface roughness and enhance the opto-electrical performance of AgNWs based transparent conductive electrode(TCE) for optoelectronic application, which require a smooth surface for high efficiency performance. In this work, we designed a hybrid metal electrode with low surface roughness fabricated by coating an AgNWs onto a metal mesh on Polyethylene terephthalate substrate (AgNW/MM/PET). The AgNW/MM/PET TCE, fabricated by a method of hot pressing after wire wound-rod coating process, exhibits a low surface roughness of 8 nm and 16.33 nm of maximum peak-to-valley value with the low sheet resistance of 0.668 Ω/sq. and a high optical transmittance of 91.25% at λ = 550 nm. In addition, the hot pressed AgNW/MM/PET TCE shows excellent mechanical stability along with long-term reliability in bending tests and strong adhesion in taping test, compared to the annealed AgNW/MM/PET TCE. Therefore, the hot pressed AgNW/MM/PET electrodes with low surface roughness and high opto-electrical performance could be a potential candidate to replace indium doped tin oxide electrodes in flexible electronic application.
•Hot pressed Silver nanowire (AgNW) on Metal mesh (MM) electrode was prepared.•Hot pressed AgNW/MM/PET electrode exhibited low surface roughness of 8 nm.•Hot pressed AgNW/MM/PET exhibits 0.668 Ω/sq. with 91.25% of transmittance.•Hot pressed AgNW/MM/PET electrode was reliable in bending and taping test.
Scope
Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a chronic recurrent inflammatory disease of the digestive tract and increases the risk of colon cancer.
Method and ...Results
This study evaluates the effects of dietary intervention with freeze‐dried plum (FDP), a natural antioxidant and anti‐inflammatory fruit with no toxicity on dextran sulfate sodium (DSS)‐induced acute and chronic experimental colitis in a mouse model and studies the molecular mechanisms of protection through the gut–liver axis. The results show that FDP decreases the levels of inflammatory mediators, which is a nitrative stress biomarker in both acute and chronic models. FDP markedly reduces DSS‐induced injury to the colonic epithelium in both acute and chronic models. In addition, FDP significantly decreases the levels of pro‐oxidant markers such as CYP2E1, iNOS, and nitrated proteins (detected by anti‐3‐NT antibody) in DSS‐induced acute and chronic colonic injury models. Furthermore, FDP markedly reduces markers of liver injury such as serum ALT/AST, antioxidant markers, and inflammatory mediators in DSS‐induced acute and chronic colonic injury.
Conclusion
These results demonstrate that the FDP exhibits a protective effect on DSS‐induced acute and chronic colonic and liver injury through the gut–liver axis via antioxidant and anti‐inflammatory properties.
In order to establish the anti‐inflammatory and antioxidant efficacy of freeze‐dried plum against ulcerative colitis, the authors employ DSS‐induced mouse models of acute and chronic UC. The data demonstrate that FDP supplementation improves shortening of colonic and small intestine compared with those in DSS‐exposed mice, and attenuates the elevated levels of inflammatory and pro‐oxidant marker proteins in the gut‐liver axis.
This study investigated how, through knowledge calibration and a causal path model, psychological distance can explain the level of satisfaction with nuclear energy policy. The investigation used ...multiple regression analysis and path analysis to explore relationships among variables. Data from 1056 adults revealed that more knowledge-calibrated individuals have more positive attitudes toward nuclear energy policy. In addition, the psychological distance influences policy satisfaction by mediation of perceived risk of nuclear energy. This study aimed to increase the understanding of the dynamic of satisfaction with and acceptance of nuclear energy policy among stakeholders. Thus, based on the construal level theory, the study addressed the importance of knowledge and psychological distance in explaining variation in satisfaction and acceptance about nuclear policy.
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