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Abstract Higher serum cholesterol levels have been associated with an increased risk of dry eye disease (DED). The relationship between statin (HMG‐CoA reductase inhibitor) use and DED in patients with hyperlipidemia remains unclear. To investigate the association between statin use and the risk of DED in patients with hyperlipidemia, we conducted a population‐based retrospective cohort study utilizing data from Taiwan's Longitudinal Generation Tracking Database. Patients were categorized into statin users and nonusers, with a 5‐year follow‐up period. The study identified patients with newly diagnosed hyperlipidemia, excluding those with prior DED diagnoses. Matching and adjustments for covariates resulted in 41,931 individuals in each group. Patients receiving statin therapy were compared with those unexposed. Cumulative exposure doses were also evaluated to assess dose–response relationships. The primary outcome was the incidence of DED diagnosed during the follow‐up period. Cox proportional hazards regression models estimated the risk of DED, and conditional logistic regression analyzed the dose–response effect of statin exposure. Among 41,931 matched pairs, statin users exhibited a slightly increased risk of developing DED compared with nonusers (adjusted hazard ratio, 1.06; 95% CI, 1.02–1.11; p

Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1β, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.

Acute pancreatitis (AP) is an inflammatory disease mediated by damage to acinar cells and pancreatic inflammation. In patients with AP, subsequent systemic inflammatory responses and multiple organs dysfunction commonly occur. Interactions between cytokines and oxidative stress greatly contribute to the amplification of uncontrolled inflammatory responses. Molecular hydrogen (H2) is a potent free radical scavenger that not only ameliorates oxidative stress but also lowers cytokine levels. The aim of the present study was to investigate the protective effects of H2 gas on AP both in vitro and in vivo. For the in vitro assessment, AR42J cells were treated with cerulein and then incubated in H2-rich or normal medium for 24 h, and for the in vivo experiment, AP was induced through a retrograde infusion of 5% sodium taurocholate into the pancreatobiliary duct (0.1 mL/100 g body weight). Wistar rats were treated with inhaled air or 2% H2 gas and sacrificed 12 h following the induction of pancreatitis. Specimens were collected and processed to measure the amylase and lipase activity levels; the myeloperoxidase activity and production levels; the cytokine mRNA expression levels; the 8-hydroxydeoxyguanosine, malondialdehyde, and glutathione levels; and the cell survival rate. Histological examinations and immunohistochemical analyses were then conducted. The results revealed significant reductions in inflammation and oxidative stress both in vitro and in vivo. Furthermore, the beneficial effects of H2 gas were associated with reductions in AR42J cell and pancreatic tissue damage. In conclusion, our results suggest that H2 gas is capable of ameliorating damage to the pancreas and AR42J cells and that H2 exerts protective effects both in vitro and in vivo on subjects with AP. Thus, the results obtained indicate that this gas may represent a novel therapy agent in the management of AP.

The aim of this study was to determine the main constituents of the essential oil isolated from Fortunella crassifolia Swingle peel by hydro-distillation, and to test the efficacy of the essential oil on antimicrobial activity. Twenty-five components, representing 92.36% of the total oil, were identified by GC-MS analysis. The essential oil showed potent antimicrobial activity against both Gram-negative (E. coli and S. typhimurium) and Gram-positive (S. aureus, B. cereus, B. subtilis, L. bulgaricus, and B. laterosporus) bacteria, together with a remarkable antifungal activity against C. albicans. In a food model of beef extract, the essential oil was observed to possess an effective capacity to control the total counts of viable bacteria. Furthermore, the essential oil showed strongly detrimental effects on the growth and morphological structure of the tested bacteria. It was suggested that the essential oil from Fortunella crassifolia Swingle peel might be used as a natural food preservative against bacteria or fungus in the food industry.

BACKGROUND: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is regarded as a promising anticancer agent, but chemoresistance affects its efficacy as a treatment strategy. Apoptosis induced by the combination of DHA and Apo2L/TRAIL has not been well documented, and the mechanisms involved remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that DHA enhances the efficacy of Apo2L/TRAIL for the treatment of pancreatic cancer. We found that combined therapy using DHA and Apo2L/TRAIL significantly enhanced apoptosis in BxPC-3 and PANC-1 cells compared with single-agent treatment in vitro. The effect of DHA was mediated through the generation of reactive oxygen species, the induction of death receptor 5 (DR5) and the modulation of apoptosis-related proteins. However, N-acetyl cysteine significantly reduced the enhanced apoptosis observed with the combination of DHA and Apo2L/TRAIL. In addition, knockdown of DR5 by small interfering RNA also significantly reduced the amount of apoptosis induced by DHA and Apo2L/TRAIL. CONCLUSIONS/SIGNIFICANCE: These results suggest that DHA enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through reactive oxygen species-mediated up-regulation of DR5.

Epithelial to mesenchymal transition (EMT) induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-κB is closely involved in the progression of EMT. Compared with HIF-1α, the correlation between NF-κB and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear.Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-κB, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1α into pancreatic cancer cells under normoxic conditions heightened NF-κB activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-κB activity in this setting attenuated the EMT phenotype.These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells.

Innovative product design is essentially an activity involving creative cognitive thinking. Therefore, research on the innovative design process and of methods, computer-aided innovation tools should be conducted based on systematic exploration based on the principles of innovative cognitive thinking. We aim to uncover some general principles that can serve as a systematic thinking framework for product designers, provide a feasible framework and method of innovative thinking for designers, and provide theoretical and methodological support for further development of computer-aided innovation platforms. This paper summarizes the sources and content of studies on the idea generation and design processes behind product innovation. Specifically, we break down the general innovative design process of products, outlining the cognitive mechanisms and propose an integrated application strategy that incorporates multiple methods. And taking "the solution program to the coking of oily sludge pyrolysis equipment" as an example, this paper demonstrated and verified the effectiveness and practicability of the method and strategy proposed. Based on the results on improvements in the equipment, the designers put forward some creative and implementable design schemes. The entire thinking process was relatively smooth and efficient. The example presented in this paper shows that the proposed method can effectively guide/assist/motivate designers to think creatively. [ABSTRACT FROM AUTHOR]

Background c-Jun NH2-terminal kinases (JNKs) are strongly activated by a stressful cellular environment, such as chemotherapy and oxidative stress. Autophagy is a protein-degradation system in which double-membrane vacuoles called autophagosomes are formed. The autophagy-related gene Beclin 1 plays a key role in this process. We previously found that autophagy was induced by dihydroartemisinin (DHA) in pancreatic cancer cells. However, little is known about the complex relationship between ROS, JNK activation, autophagy induction, and Beclin 1 expression. Methods Cell viability and CCK-8 assays were carried out to determine the cell proliferation; small interfering RNAs (siRNAs) were used to knockdown c-Jun NH2-terminal kinases (JNK1/2) genes; western blot was performed to detect the protein expression of LC3, JNK, Beclin 1, caspase 3 and β-actin; production of intracellular ROS was analyzed using FACS flow cytometry; autophagy induction was confirmed by electron microscopy. Results In the present study, we explored the role of DHA and Beclin 1 expression in autophagy. DHA-treated cells showed autophagy characteristics, and DHA also activated the JNK pathway and up-regulated the expression of Beclin 1. Conversely, blocking JNK signaling inhibited Beclin 1 up-regulation. JNK activation was found to primarily depend on reactive oxygen species (ROS) resulting from the DHA treatment. Moreover, JNK pathway inhibition and Beclin 1 silencing prevented the induction of DHA-induced autophagy. Conclusions These results suggest that the induction of autophagy by DHA is required for JNK-mediated Beclin 1 expression. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the main constituents of the essential oil isolated from Fortunella crassifolia Swingle peel by hydro-distillation, and to test the efficacy of the essential oil on antimicrobial activity. Twenty-five components, representing 92.36% of the total oil, were identified by GC-MS analysis. The essential oil showed potent antimicrobial activity against both Gram-negative (E. coli and S. typhimurium) and Gram-positive (S. aureus, B. cereus, B. subtilis, L. bulgaricus, and B. laterosporus) bacteria, together with a remarkable antifungal activity against C. albicans. In a food model of beef extract, the essential oil was observed to possess an effective capacity to control the total counts of viable bacteria. Furthermore, the essential oil showed strongly detrimental effects on the growth and morphological structure of the tested bacteria. It was suggested that the essential oil from Fortunella crassifolia Swingle peel might be used as a natural food preservative against bacteria or fungus in the food industry. [ABSTRACT FROM AUTHOR]

Background: Epithelial to mesenchymal transition (EMT) induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-&kgr;B is closely involved in the progression of EMT. Compared with HIF-1&agr;, the correlation between NF-&kgr;B and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear. Methodology/Principal Findings: Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1&agr; (HIF-1&agr;) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-&kgr;B, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1&agr; into pancreatic cancer cells under normoxic conditions heightened NF-&kgr;B activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-&kgr;B activity in this setting attenuated the EMT phenotype. Conclusions/Significance: These results suggest that hypoxia or overexpression of HIF-1&agr; induces the EMT that is largely dependent on NF-&kgr;B in pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Purpose To observe whether early cleavage can be a predictor of embryo developmental potential, pregnancy and implantation rates. Methods A total of 9,544 embryos in 1,095 in vitro fertilization or intracytoplasmic sperm injection cycles were observed with regard to the appearance of early cleavage at 25-29 h post-insemination. Results A significantly higher proportion of excellent quality embryos were observed in the early cleavage group compared to the late cleavage group (52.5 versus 28.9%, P<0.01). In the early cleavage group there was also a higher rate of pregnancy per transfer compared with the late cleavage group (38.7 versus 26.3%, P<0.01). In addition, we found that transfer of only one early cleavage embryo resulted in a high pregnancy rate (38.5%) and a low multiple pregnancy rate (18.0%). Conclusion Early cleavage is a strong indicator of embryo quality, and may be used as an additional criterion in the selection of embryos for transfer to increase pregnancy rate and reduce multiple pregnancy rate. [ABSTRACT FROM AUTHOR]

Kerfless technology is a promising alternative for reducing cost and providing flexible thin crystals in silicon-based semiconductors. In this work we propose a protruded seed substrate technology to prepare flexible monocrystalline Si thin film economically. Grooved seed substrate is fabricated by using SiNx thin film as a mask for the wet-etching and thermal oxidation process. After the SiNx layer on the wedged strip is removed by hot phosphoric acid, the pre-defined structured substrate is achieved with the top of the strip serving as the seed site where there is no oxide layer. And a preferred growth of epitaxial Si on the substrate is performed by introducing an intermittent feed method for silicon source gas. The technique in this paper obviously enhances the mechanical stability of the seed structure and the growth behavior on the seed sites, compared with our previous techniques, so this technique promises to be used in the industrial fabrication of flexible Si-based devices. [ABSTRACT FROM AUTHOR]

This paper describes the successful fabrication of 4H-SiC junction barrier Schottky (JBS) rectifiers with a linearly graded field limiting ring (LG-FLR). Linearly variable ring spacings for the FLR termination are applied to improve the blocking voltage by reducing the peak surface electric field at the edge termination region, which acts like a variable lateral doping profile resulting in a gradual field distribution. The experimental results demonstrate a breakdown voltage of 5 kV at the reverse leakage current density of 2 mA/cm2 (about 80% of the theoretical value). Detailed numerical simulations show that the proposed termination structure provides a uniform electric field profile compared to the conventional FLR termination, which is responsible for 45% improvement in the reverse blocking voltage despite a 3.7% longer total termination length. [ABSTRACT FROM AUTHOR]