The disruption of microvascular barrier in response to advanced glycation end products (AGEs) stimulation contributes to vasculopathy associated with diabetes mellitus. Here, to study the role of Src and its association with moesin, VE-cadherin and focal adhesion kinase (FAK) in AGE-induced vascular hyperpermeability, we verified that AGE induced phosphorylation of Src, causing increased permeability in HUVECs. Cells over-expressed Src displayed a higher permeability after AGE treatment, accompanied with more obvious F-actin rearrangement. Activation of Src with pcDNA3/flag-SrcY530F alone duplicated these effects. Inhibition of Src with siRNA, PP2 or pcDNA3/flag-SrcK298M abolished these effects. The pulmonary microvascular endothelial cells (PMVECs) isolated from receptor for AGEs (RAGE)-knockout mice decreased the phosphorylation of Src and attenuated the barrier dysfunction after AGE-treatment. In vivo study showed that the exudation of dextran from mesenteric venules was increased in AGE-treated mouse. This was attenuated in RAGE knockout or PP2-pretreated mice. Up-regulation of Src activity induced the phosphorylation of moesin, as well as activation and dissociation of VE-cadherin, while down-regulation of Src abolished these effects. FAK was also proved to interact with Src in HUVECs stimulated with AGEs. Our studies demonstrated that Src plays a critical role in AGE-induced microvascular hyperpermeability by phosphorylating moesin, VE-cadherin, and FAK respectively.

A diverse array of cellular stresses can lead to accumulation of misfolded or unfolded proteins in endoplasmic reticulum (ER), which subsequently elicits ER stress. Inositol-requiring enzyme 1α (IRE1α) is the most sensitive of the three unfolded protein response (UPR) branches which are triggered to cope with ER stress in mammalian cells. IRE1α signaling is quite context-specific on account of many adaptor and modulator proteins that directly interact with it, including heat shock proteins (HSPs), RING finger protein 13 (RNF13), poly (ADP-ribose) polymerase 16 (PARP16), Bax/Bak, and Bax inhibitor-1 (BI-1). The activated IRE1α triggers different downstream pathways depending on the UPRosome formed by distinct modulator proteins. At the initial phase of ER stress, IRE1α-XBP1 axis functions as an adaptive response. While ER stress sustains or intensifies, signals shift to apoptotic responses. Furthermore, IRE1α signaling can be exploited to the development of a wide range of prevalent human diseases, with cancer the most characterized. Here we provide an overview of recent insights into the complex IRE1α signaling network which makes IRE1α an intriguing cell fate switch. Besides, the functional relevance is presented since IRE1α activation also participates in some other physiological processes beyond protein-folding status.

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In this study, a strategy for the fabrication of zirconia-polyimide (ZrO 2 -PI) nanohybrid films with high permittivity (high-k), thermal stability, and excellent mechanical properties has been developed. A colloidal suspension of ZrO 2 nanorods was prepared using the facile microwave-hydrothermal treatment approach. The ZrO 2 -PI nanohybrid film was fabricated by casting an aqueous solution containing water-soluble poly(amic acid) ammonium salt (PAS) and water-dispersible ZrO 2 nanorods followed by thermal imidization. Atomic force microscopy and scanning electron microscopy images indicated that the ZrO 2 nanorods were uniformly dispersed in the PI matrix. Because of the high permittivity of the ZrO 2 nanorods and good compatibility between polyimide and ZrO 2 as well as the nanosize of ZrO 2 , the permittivity increased to 5.1 as the ZrO 2 concentration reached 10% at 10 Hz, while the dielectric loss was as low as 0.05 at 10 Hz. The prepared ZrO 2 -PI nanohybrid films had excellent heat resistance with quite low coefficients of thermal expansion (CTE), as low as 16.3 ppm/K. The ZrO 2 -PI nanohybrid films have excellent thermal stability and good mechanical flexibility. Moreover, no distinct changes were observed for the PAS solution over a storage time of 3 months, after which the nanohybrid film could still be successfully synthesized by thermal imidization. In addition, the water uptake of the ZrO 2 -PI nanohybrid film was approximately 2.5% under 60% relative humidity. The high stability of the PAS precursor, good flexibility, enhanced permittivity, and low CTE behavior of the ZrO 2 -PI nanohybrid films could make this strategy attractive for the ecofriendly design of dielectric polymer nanohybrids as well as for the fabrication of nanohybrid films with potential applications in high charge-storage capacitors and organic field-effect transistors (OFETs) in the flexible electronics industry.

Introduction To describe the clinical and laboratory features of systemic lupus erythematosus (SLE) enteritis and to establish a predictive model of risk and severity of lupus enteritis (LE). Methods Records of patients with SLE complaining about acute digestive symptoms were reviewed. The predictive nomogram for the diagnosis of LE was constructed by using R. The accuracy of the model was tested with correction curves. The receiver operating characteristic curve (ROC curve) program and a Decision curve analysis (DCA) were used for the verification of LE model. Receiver operating characteristic curve was also employed for evaluation of factors in the prediction of severity of LE. Results During the eight year period, 46 patients were in the LE group, while 32 were in the non-LE group. Abdominal pain, emesis, D-dimer >5 μg/mL, hypo-C3, and anti-SSA positive remained statistically significant and were included into the prediction model. Area under the curve (AUC) of ROC curve in this model was 0.909. Correction curve indicated consistency between the predicted rate and actual diagnostic rates. The DCA showed that the LE model was of benefit. Forty-four patients were included in developing the prediction model of LE severity. Infection, SLE disease activity index (SLEDAI), CT score, and new CT score were validated as risk factors for LE severity. The AUC of the combined SLEDAI, infection and new CT score were 0.870. Conclusion The LE model exhibits good predictive ability to assess LE risk in SLE patients with acute digestive symptoms. The combination of SLEDAI, infection, and new CT score could improve the assessment of LE severity.