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Background: We intended to investigate the role and regulatory mechanism of EPS8L3 in increase the development of pancreatic cancer (PC). Methods: In order to analyze the relationship between EPS8L3 level and clinicopathological indicators of PC patients, qRT-PCR was used to detect the expression of EPS8L3 in tumor specimens of 40 PC patients. EPS8L3 knockdown models were then constructed in PC cell lines. Furthermore, the effect of EPS8L3 on PC cell function was analyzed by CCK-8 and Transwell assay. Dual luciferase reporter gene assay and recovery assay were used to further investigate the underlying mechanism. Results: qRT-PCR results indicated that EPS8L3 was highly expressed in PC tissues compared with adjacent ones. At the same time, the incidence of distant metastasis was higher in PC patients with high EPS8L3 level. In vitro analysis such as CCK-8 and Transwell experimentations indicated that knockdown of EPS8L3 markedly inhibited the proliferative and metastatic ability. Bio-informatics together with luciferase report assay proposing that EPS8L3 can target GSK3B. Western Blot results revealed that knockdown of EPS8L3 markedly reduced the GSK3B expression in PC cells, and there was a positively associated between the two in PC cells. In addition, the recovery experimentation proved that EPS8L3 and GSK3B have a mutual regulation effect. Overexpression of GSK3B can reversal the prohibitive effect of EPS8L3 knockdown on the malignant development of PC cells, thereby jointly regulating the occurrence and development of PC. Conclusions: EPS8L3 promotes the development of PC by regulating GSK3B, suggesting that EPS8L3 can be used as a biomarker for early diagnosis and treatment of PC.

The exploration of efficient and environmentally friendly oxidation method is highly desirable to overcome the critical problems of poor selectivity and heavy metal contamination for the fine chemicals industry. Herein, a self-supported 3D Se-Ni5P4 nanosheet electrocatalyst was rationally designed and fabricated. Benefiting from the synergistic effect of aminoxyl radical and mesoporous Se-Ni5P4/GF, an excellent performance of ≥98% selectivity and 33.12 kg/(m3·h) space-time yield was obtained for sterol intermediate oxidation with the enhanced mass transfer effect of the continuous flow system. The doping of anionic selenium and phosphorus modulated the electronic structure of Se-Ni5P4, and the oxyhydroxides generated by surface reconstruction accelerated the turnover of TEMPO, thereby enhancing the intrinsic electrocatalytic activity. A scale-up experiment was conducted with stacked-flow electrolyzer demonstrated the application potential. This work provided an efficient synergistic electrocatalytic strategy to facilitate rapid electron and mass transfer for electrochemical alcohol oxidation and highlighted the potential for practical electrosynthesis applications.

Background: Allicin, a major component of garlic, is regarded as a cardioprotective agent and is associated with increased endothelial function. Methods: The effects of allicin on lipopolysaccharide (LPS)-induced vascular oxidative stress and inflammation in cultured human umbilical vein endothelial cells (HUVECs) and the mechanisms underlying these effects were studied. The protective effects were measured using cell viability, a lactate dehydrogenase (LDH) assay and cell apoptosis as indicators, and the anti-oxidative activity was determined by measuring reactive oxygen species (ROS) generation, oxidative products and endogenous antioxidant enzyme activities. HUVEC mitochondrial function was assessed by determining mitochondrial membrane potential (MMP) collapse, cytochrome c production and mitochondrial ATP release. To investigate the potential underlying mechanisms, we also measured the expression of dynamic mitochondrial proteins using western blotting. Furthermore, we evaluated the Nrf2 antioxidant signaling pathway using an enzyme-linked immunosorbent assay (ELISA). Results: Our results demonstrated that allicin enhanced HUVEC proliferation, which was suppressed by LPS exposure, and LDH release. Allicin ameliorated LPS-induced apoptosis, suppressed ROS overproduction, reduced lipid peroxidation and decreased the endogenous antioxidant enzyme activities in HUVECs. These protective effects were associated with the inhibition of mitochondrial dysfunction as indicated by decreases in the MMP collapse, cytochrome c synthesis and mitochondrial ATP release. In addition, allicin attenuated the LPS-induced inflammatory responses, including endothelial cell adhesion and TNF-α and IL-8 production. Furthermore, allicin increased the expression of LXRα in a dose-dependent manner. Allicin-induced attenuation of inflammation was inhibited by LXRα siRNA treatment. Finally, allicin activated NF-E2-related factor 2 (Nrf2), which controls the defense against oxidative stress and inflammation. Conclusions: Taken together, the present data suggest that allicin attenuated the LPS-induced vascular injury process, which may be closely related to the oxidative stress and inflammatory response in HUVECs. Allicin modulated Nrf2 activation and protected the cells against LPS-induced vascular injury. Our findings suggest that allicin attenuated the LPS-induced inflammatory response in blood vessels.

Background: endoscopic submucosal dissection (ESD) has been widely recognized by patients and doctors due to its advantages in early gastric cancer (EGC). The accurate prediction of the risk of lymph node metastasis (LNM) in EGC is important to select suitable treatments with this procedure for patients. Unfortunately, the accuracy of endoscopic ultrasound and computed tomography in the diagnosis of EGC lymph node status is extremely limited. The purpose of the present study was to establish an LNM nomogram risk model of early gastric cancer patients based on clinical data, to guide treatment for clinicians. Methods: a retrospective examination of the records of EGC patients undergoing radical gastrectomy from August 2012 to August 2019 in the Gastrointestinal Center of Subei People’s Hospital was performed. The clinicopathological data were classified into a training set and validation set according to the time. Univariate and multivariate analyses were performed to identify risk factors related to LNM. A risk model for predicting the occurrence of LNM in EGC was established and validated. Results: of the 503 EGC patients, 78 (15.5 %) had lymph node metastasis. Logistic stepwise regression analysis showed that the predictive factors included sex, tumor location, tumor diameter, differentiation, ulcer and lymphatic vascular invasion. The discrimination of the LNM prediction model was satisfactory with an AUC of 0.8033 (internal validation) and 0.7353 (external validation). The correction effect of the calibration was satisfactory and the DCA decision curve analysis showed a strong clinical practicability. Conclusion: the nomogram risk prediction model of LNM has been established for EGC patients to assist in formulating personalized treatment plans.

Epigallocatechin-3-gallate (EGCG) has been shown to possess anti-inflammatory effects. Microcystin-LR (MC-LR) is a potent toxin and our past research suggested that it also mediated human umbilical vein endothelial cell (HUVEC) injury. The aim of this study was to investigate the effects of EGCG on MC-LR-induced oxidative stress and inflammatory responses in HUVECs. HUVECs were stimulated with MC-LR in the presence or absence of EGCG. MC-LR (40 μM) significantly increased cell death and decreased cell viability, migration, and tube formation, whereas EGCG (50 μM) inhibited these effects. Furthermore, the results indicated that EGCG inhibited the production of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in MC-LR-stimulated HUVECs. Compared with MC-LR, EGCG significantly increased superoxide dismutase (SOD) and glutathione (GSH) levels and decreased malondialdehyde (MDA) levels. Moreover, the analysis indicated that EGCG suppressed MC-LR-induced NF-κB activation. In conclusion, the effects of EGCG were associated with inhibition of the NF-κB signaling pathway, which resulted in decreased ROS and TNF-α, thereby attenuating MC-LR-mediated oxidative and inflammatory responses.

It is known that irisin increases total body energy expenditure, decreases body weight, and enhances insulin sensitivity. Although previous studies have demonstrated that irisin induces vascular endothelial cell (EC) angiogenesis, the molecular mechanisms underlying irisin-induced angiogenesis under conditions reflecting atherosclerosis are not known. The aim of the present study is to investigate whether irisin could inhibit oxidized low-density lipoprotein (oxLDL) impaired angiogenesis. We investigated the effect of irisin on angiogenesis in vitro by evaluating cell viability, cell migration, and the capacity to form capillary-like tubes using human umbilical vein endothelial cells and human microvascular endothelial cells (HUVECs and HMEC-1) that were treated with oxLDL. We also evaluated the effects of irisin on angiogenesis in vivo by Matrigel plug angiogenesis assay and in a chicken embryo membrane (CAM) model. Our results demonstrated that irisin increased oxLDL-treated EC viability as well as migration and tube formation. Moreover, oxLDL inhibited angiogenic response in vivo, both in the Matrigel plug angiogenesis assay and in the CAM model, and was attenuated by irisin. Furthermore, irisin decreased apoptosis, inflammatory cytokines, and intracellular reactive oxygen species (ROS) levels in oxLDL-treated EC. In addition, we found that irisin upregulated pAkt/mTOR/Nrf2 in oxLDL-treated EC. Both mTOR/Nrf2 shRNA and LY294002 could inhibit the protective effect of irisin. Taken together these results, they suggested that irisin attenuates oxLDL-induced vascular injury by activating the Akt/mTOR/Nrf2 pathway. Our findings suggest that irisin attenuates oxLDL-induced blood vessel injury.

The characteristics of cloud-to-ground (CG) lightning for nine hailstorms in Yunnan province of China are analyzed statistically. It is determined that the hailstorms were found to present dominant negative CG lightning flashes at any given stage. One specific hailstorm occurring on July 16, 2006, is analyzed in detail by using the data from a CG lightning location network and Doppler radar. This severe hailstorm, which exhibited strong vertical development with cloud tops reaching 15.9 km, produced hailstones as large as 15 mm and had a lifespan of 3 h and 12 min. The total CG lightning within the hailstorm showed high levels of activity with flash rates of up to 79 fl/5 min. The analysis of the storm cell’s lifecycle shows similar trends between the CG lightning flash rates and radar-derived parameters. Cloud-to-ground flashes tended to initiate within the cloud region with reflectivity of more than 30 dBZ at the −10 °C isotherm height. A distinct increase in CG flash rate is shown during the rapid development stages of hailstorms. The CG lightning jump pattern appears to be an effective tool for short-term forecasting of possible occurrences of severe weather.