The acts of opening and closing the eyes are of importance for congenital blindness: Evidence from resting-state fMRI.

Volitional eye closure is observed only in conscious and awake humans, and is rare in animals. It is believed that eye closure can focus one's attention inward and facilitate activities such as meditation and mental imagery. Congenital blind individuals are also required to close their eyes for these activities. Resting-state functional magnetic resonance imaging (RS-fMRI) studies have found robust differences between the eyes-closed (EC) and eyes-open (EO) conditions in some brain regions in the sighted. This study analyzed data from 21 congenital blind individuals and 21 sighted controls by using amplitude of low-frequency fluctuation (ALFF) of RS-fMRI. The blind group and the sighted group shared similar pattern of differences between the EC and EO condition: ALFF was higher in the EC condition than the EO condition in the bilateral primary sensorimotor cortex, bilateral supplementary motor area, and inferior occipital cortex, while ALFF was lower in the EC condition than the EO condition in the medial prefrontal cortex, highlighting the "nature" effect on the difference between the EC and EO conditions. The results of other matrices such as fractional ALFF (fALFF) and regional homogeneity (ReHo) showed similar patterns to that of ALFF. Moreover, no significant difference was observed between the EC-EO pattern of the two subgroups of congenital blind (i.e., with and without light perception), suggesting that the EC-EO difference is irrespective of residual light perception which reinforced the "nature" effect. We also found between-group differences, i.e., more probably "nurture effect", in the posterior insula and fusiform. Our results suggest that the acts of closing and opening the eyes are of importance for the congenital blind, and that these actions and their differences might be inherent in the nature of humans.

The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population.

BACKGROUND: A cross-talk between Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) plays a vital role in aortic pathophysiology. The objective of this study was to evaluate the interactions between TLR4 and MMP9 polymorphisms in the risk of aortic aneurysm (AA) and its subtypes. METHODS: KASP method was used to detect polymorphisms of TLR4 (rs11536889 and rs1927914) and MMP9 (rs17576) in 472 AA patients and 498 controls. According to location and size, AA patients were further classified into abdominal AA (AAA), thoracic AA (TAA), and large AA (>5.0 cm), small AA(≤5.0 cm), respectively. RESULTS: The significant interaction effect of TLR4rs1927914 with MMP9rs17576 polymorphisms was observed for the risk of TAA (Pinteraction = 0.038, OR = 6.186) and large AA (Pinteraction = 0.044, OR = 5.892). There were epistatic effects between TLR4rs1927914 and MMP9rs17576 polymorphisms on the risk of overall AA, AAA, TAA and large AA when they were present together. Moreover, the cumulative effects of the pairwise interaction TLR4rs1927914-MMP9rs17576 were associated with an increased risk of overall AA (Ptrend = 0.032) and AAA (Ptrend = 0.031). CONCLUSIONS: The novel interaction between TLR4rs1927914 and MMP9rs17576 polymorphisms could increase the risk of AA disease or its subtypes by exerting epistatic and cumulative effects.

Serum matrix metalloproteinase-9 is a valuable biomarker for identification of abdominal and thoracic aortic aneurysm: a case-control study.

BACKGROUND: Matrix metalloproteinase-9 (MMP9) has been reported to play a key role in the pathogenesis of aortic aneurysm. However, few studies have assessed serum MMP9 levels in both abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). In this study, we investigated the serum levels of MMP9 in aortic aneurysm to evaluate its predictive and diagnostic efficacy for AAA and TAA, and explored the association of MMP9 with circulating laboratory markers. METHODS: A total of 296 subjects were enrolled, including 105 AAA patients, 79 TAA patients and 112 healthy controls. The levels of serum MMP9 were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to control group, both AAA and TAA patients had higher serum MMP9 levels in the overall comparison and subgroup analysis based on subjects aged<65 years, either male or female, hypertension, non-diabetes and non-hyperlipidemia (all P<0.05). Moreover, MMP9 levels were significantly higher in TAA group than those in AAA group in the total comparison, and this discrepancy was also found in the non-diabetes, non-hyperlipidemia and aortic diameter ≥ 5.5 cm subgroup analysis. Serum MMP9 levels were influenced by age and hypertension. There was a positive association of serum MMP9 with CRP (r = 0.33, P < 0.001) and Hcy (r = 0.199, P = 0.033). Multiple logistic analyses showed that serum MMP9 was an independent risk factor for AAA and TAA. Based on receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of MMP9 for predicting TAA was 0.83 with 70% sensitivity and 91% specificity, while the AUC of MMP9 to detect AAA was 0.69 and the sensitivity and specificity were 50% and 88%. CONCLUSIONS: Serum MMP9 was closely related to the existence of aortic aneurysms and could be a valuable marker for the discrimination of aortic aneurysm, especially for TAA.

Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA.

Sunitinib resistance is a major challenge for advanced renal cell carcinoma (RCC). Understanding the underlying mechanisms and developing effective strategies against sunitinib resistance are highly desired in the clinic. Here we identified an lncRNA, named lncARSR (lncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response. Therefore, lncARSR may serve as a predictor and a potential therapeutic target for sunitinib resistance.

[Influence of different designs of marginal preparation on stress distribution in the mandibular premolar restored with endocrown].

OBJECTIVE: To evaluate the effect of different designs of marginal preparation on stress distribution in the mandibular premolar restored with endocrown using three-dimensional finite element method. METHODS: Four models with different designs of marginal preparation, including the flat margin, 90° shoulder, 135° shoulder and chamfer shoulder, were established to imitate mandibular first premolar restored with endocrown. A load of 100 N was applied to the intersection of the long axis and the occlusal surface, either parallel or with an angle of 45° to the long axis of the tooth. The maximum values of Von Mises stress and the stress distribution around the cervical region of the abutment and the endocrown with different designs of marginal preparation were analyzed. RESULTS: The load parallel to the long axis of the tooth caused obvious stress concentration in the lingual portions of both the cervical region of the tooth tissue and the restoration. The stress distribution characteristics on the cervical region of the models with a flat margin and a 90° shoulder were more uniform than those in the models with a 135° shoulder and chamfer shoulder. Loading at 45° to the long axis caused stress concentration mainly on the buccal portion of the cervical region, and the model with a flat margin showed the most favorable stress distribution patterns with a greater maximum Von Mises stress under this circumstance than that with a parallel loading. Irrespective of the loading direction, the stress value was the lowest in the flat margin model, where the stress value in the cervical region of the endocrown was greater than that in the counterpart of the tooth tissue. The stress level on the enamel was higher than that on the dentin nearby in the flat margin model. CONCLUSIONS: From the stress distribution point of view, endocrowns with flat margin followed by a 90° shoulder are recommended.

Protective effect of O6-methylguanine-DNA-methyltransferase on mammalian cells.

BACKGROUND: O(6)-methylguanine-DNA-methyltransferase (MGMT) is a specific DNA revising enzyme transferring alkylated groups from DNA to its cysteine residue to avoid the abnormal twisting of DNA. Therefore, it is one of the drug resistant genes targeted in the treatment of cancer. This study explored the protective effect of MGMT gene transferred into mammalian cells. METHODS: Mammalian expression vector containing the MGMT gene cloned from human hepatocytes by RT-PCR was constructed and transferred into K562 cells and human peripheral blood mononuclear cells (PBMCs) via liposome, then assayed for gene expression at RNA and protein levels. MTT assay was used to check the drug resistance of cells transfected with MGMT gene. RESULTS: MGMT gene was successfully cloned. Real-time PCR showed that the mRNA expression in gene transfected groups in K562 cell line and PBMC were 13.4 and 4.0 times that of the empty vector transfected groups respectively. RESULTS: of Western blotting showed distinct higher expression of MGMT in gene transfected group than in other two groups. The IC(50) values increased to 7 and 2 times that of the original values respectively in stable transfected K562 cells and transient transfected PBMC. CONCLUSION: The alkylating resistance of eukaryotic cells is enhanced after being transfected with MGMT gene which protein product performs the protective function, and may provide the reference for the protective model of peripheral blood cells in cancer chemotherapy.