Melt memory in random ethylene-1-alkene copolymers.

Chain flexibility or stiffness based polymer conformation plays a crucial role in affecting the dynamics and kinetics of polymers, which is related to the hierarchical architecture of chains. A series of random copolymers of ethylene and 1-alkenes including 1-hexene, 1-octene, and 1-dodecene were synthesized with metallocene catalysts. The crystallization behavior and memory effect in random ethylene-1-alkene copolymers with different side groups were investigated via differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). Rheological tests were performed for understanding their dynamical behavior. The results show that the melting peak and the viscosity decrease but the orthorhombic crystal dimensions increase with co-unit contents increasing in the copolymers. It was found that the scaling relationship between the zero shear viscosity (η0) and molecular weight (Mn) of the copolymers containing ethylene-1-hexene and ethylene-1-octene is 3.6, which is higher than the classical scaling value of 3.4. The memory of crystals in the melt is enhanced with the increase of 1-alkene contents but is independent of the types of 1-alkenes. The enhanced melt memory effect in the copolymers was proposed due to the effect of the 1-alkene based side groups on the dynamics of polymer chains. The present work would be helpful to understand the chain stiffness based polymer dynamics and processing of polyolefins and copolymers prepared with the metallocene catalyst.

Factors that determine a Patient's willingness to physician selection in online healthcare communities: A trust theory perspective.

Health care users and patients are increasingly using online health communities to seek medical service, especially during the COVID-19 epidemic. The factors that determine the online trust between physicians and patients perplex the stakeholders for a long time. Based on the trust theory, this study explored the influence of physicians' personal quality and online reputation on patients' selection. A longitudinal panel data collection exercise, covering 11905 physicians on haodf. com, was conducted on May 20, 2018, May 22, 2019 and May 25, 2020. The random effect models are used to test our hypothesis. Results show that physicians' quality (competence, benevolence, and integrity) and online reputation (online reviews and online rating) can significantly affect patients' selection. Moreover, the physician's gender can enhance the influence of online reputation on patients' selection. As online healthcare community becomes an increasingly appealing channel for health, the frequency of the physician's quality information updating and the quality of online service are equally important to online physician-patient trust.

Hepatic insulin resistance induced by mitochondrial oxidative stress can be ameliorated by sphingosine 1-phosphate.

The bioactive lipid mediator sphingosine 1-phosphate (S1P) is considered to be involved in the development of insulin resistance (IR) via effects on oxidative stress; the mechanism however is not yet fully revealed. To this end, we investigated the role and mechanism of S1P on hepatic IR. We found that treatment of the normal human liver cell LO2 with 1000 nM insulin for 48 h reduced glucose uptake and increased serine phosphorylation of insulin receptor substrate-1, indicating a reduction in insulin receptor signaling. Moreover, the same concentration of insulin caused accumulation of reactive oxygen species (ROS) in the cytosol and mitochondria, and enhanced expression of the antioxidant transcription factor (Nrf2) and upregulated Nrf2 nuclear translocation. Using known inhibitors and donors of ROS (H2O2, ·O2-, ·OH), the results demonstrated the differential roles for the specific ROS in regulating IR in LO2 cells, with H2O2 having a more significant inhibitory role compared with ·O2- and ·OH. Cell treatment with S1P at 0.1-5.0 µM reversed the effects of high insulin concentrations on ROS generation, glucose uptake, and insulin signaling. H2O2 also reversed the beneficial effects of S1P in alleviating IR. These results show that H2O2 signaling plays a key determinant in hepatic IR induced by insulin. S1P can ameliorate hepatic IR by reducing mitochondrial ROS generation, and the possible anti-IR effect mechanism may be involved in H2O2 signaling.

miR-503-3p induces apoptosis of lung cancer cells by regulating p21 and CDK4 expression.

Studies have shown that microRNAs (miRNAs) can promote or suppress tumor growth and therefore act as targets for cancer therapy. Hsa-miR-503-5p, a mature miRNA derived from 5' ends of pre-miR-503, has been proved to regulate cell proliferation, transformation, migration and invasion. However, the biological function of miR-503-3p derived from 3' ends of pre-miR-503 has never been reported. In current study, we found that miR-503-3p inhibits lung cancer cell viability and induces cell apoptosis. To better understand the molecular mechanism underlying the miR-503-3p participating in this process, PCR array and RNA-sequencing (RNA-seq) were performed and some differential expression genes were discovered between NC and miR-503-3p treated groups. Biological interaction network showed that p21 and CDK4 are the most important proteins involving miR-503-3p signal pathway. Dual-luciferase assay results shown miR-503-3p directly regulates the expression of p21 by targeting 3'-UTR of its mRNA. These results shed light on the potential roles of miR-503-3p, indicating that it may act as an anti-oncogene factor to inhibit lung cancer cell viability.

Propoxur enhances MMP-2 expression and the corresponding invasion of human breast cancer cells via the ERK/Nrf2 signaling pathway.

Propoxur is considered a prime etiological suspect of increasing tumor incidence, but the role is still undefined. In this study, two human breast cancer cells lines, MCF-7 and MDA-MB-231 cells, were used as cell models. Cells were respectively treated with 0, 0.01, 1, or 100 µM propoxur. PD98059, a MEK inhibitor, was administered to block the ERK/MAPK pathway. Migration and reactive oxygen species were measured by wound healing and Transwell assays, and flow cytometry. Protein expression and subcellular location were detected by western blotting and immunofluorescence staining, respectively. Results showed that propoxur treatment enhanced cell migration and invasion in a dose-dependent manner, while MMP-2 expression, but not MMP-9, was significantly increased in two cell lines. Meanwhile, the treatment increased intracellular reactive oxygen species, Nrf2 expression and nuclear translocation, and ERK1/2 phosphorylation. Inversely, inhibition of ERK1/2 activation with PD98059 significantly attenuated propoxur-induced Nrf2 expression and nuclear translocation. Moreover, PD98059 suppressed propoxur-induced cell migration and invasion, and MMP-2 overexpression. Collectively, these results indicate that propoxur can trigger reactive oxygen species overproduction, further promoting breast cancer cell migration and invasion by regulating the ERK/Nrf2 signaling pathways.

sMICA as novel and early predictors for acute myocardial infarction.

BACKGROUND AND AIMS: MHC class I polypeptide-related chain A (MICA) molecule is induced in response to viral infection, various types of stress, such as endoplasmic reticulum stress, and ischemia or/and reperfusion, by which MICA was shed from the cell surface into the extracellular domain, generating a soluble form (sMICA). In the present study, we designed to investigate the serum sMICA level in patients with AMI and determine whether sMICA could be an early biomarker for diagnosis of AMI. METHODS: There were 103 patients who presented with first-time AMI that was assessed after the incident. The control group consisted of 103 healthy volunteers. Serum levels of sMICA and Troponin T were detected by the specific ELISA kits. RESULTS: Serum levels of sMICA reach the peaks [(1.34 ± .18 and 1.72 ± .20)n/l] at 6-12 h and serum levels of cTnT reach the peaks [(1.16 ± .28 and 1.14 ± .34)n/l] at 12-24 h. Both of them were significantly higher than the healthy controls [(.168 ± .014) n/l, p = .000] for sMICA and [(.13 ± .06) n/l, p = .000] for Troponin T (cTnT). sMICA is more sensitive in the early diagnosis of AMI than cTnT. The combined ROC analysis revealed an AUC value of .78 (95 % CI .69-.83) in discriminating AMI patients from healthy controls. CONCLUSIONS: We have detected high levels of sMICA in patients with AMI. Elevated serum sMICA may be a novel biomarker for the early detection of myocardial injury in humans.

Claudin-4 is required for vasculogenic mimicry formation in human breast cancer cells.

Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Claudins are aberrantly expressed in aggressive breast cancer. However, the relationship between claudins and VM formation is not clear. We examined VM in two human breast cancer cell lines with different aggressive capabilities (MDA-MB-231 and MCF-7 cells) and one human umbilical vein endothelial cell line (HUVEC). Both HUVEC and MDA-MB-231 cells formed vascular channels in Matrigel cultures, while MCF-7 cells did not. Western blot analysis revealed a possible correlation between claudin-4 and -6 expression in breast cancer cell lines and tumor aggressiveness, with protein levels correlating with the ability to form vascular channels. Treatment of MDA-MB-231 and HUVEC cells with claudin-4 monoclonal antibodies completely inhibited the ability of cells to form vascular channels. Moreover, knockdown of claudin-4 by short hairpin RNA completely inhibited tubule formation in MDA-MB-231 cells. Overexpression of claudin-4 in MCF-7 cells induced formation of vascular channels. Immunocytochemistry revealed that membranous claudin-4 protein was significantly associated with vascular channel formation. Collectively, these results indicate that claudin-4 may play a critical role in VM in human breast cancer cells, opening new opportunities to improve aggressive breast cancer therapy.