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Papillary thyroid carcinoma (PTC) is the most frequent histological type of differentiated thyroid carcinoma. Long noncoding RNAs (lncRNAs) have been widely reported to play a key role in human malignancies, and PTC is included. This study aimed to find out the functions and mechanism of lncRNA LINC00475 in PTC. LINC00475 was upregulated in PTC cells and was mainly located in the cytoplasm according to reverse-transcription polymerase chain reaction analyses and subcellular fractionation assays. As shown by cell counting kit-8 assays, ethynyl deoxyuridine incorporation assays, wound healing assays, and transwell assays, LINC00475 knockdown suppressed cell viability, proliferation, migration, and invasion. Mechanistically, LINC00475 upregulated the expression of messenger RNA zinc finger CCHC-type containing 12 (ZCCHC12) by binding to miR-376c-3p. ZCCHC12 was a direct target gene of miR-376c-3p in PTC cells. The relationship between miR-376c-3p and LINC00475 (or ZCCHC12) in PTC cells was probed by luciferase reporter assays, RNA pulldown assays, and RNA immunoprecipitation assays. In addition, both mRNA and protein levels of ZCCHC12 were downregulated due to miR-376c-3p overexpression or LINC00475 silencing. ZCCHC12 overexpression partially reversed the suppressive effect of LINC00475 knockdown on malignant behaviors of PTC cells. In conclusion, LINC00475 promotes PTC cell proliferation, migration, and invasion by upregulating ZCCHC12 via the interaction with miR-376c-3p.

Equivalent single-degree-of-freedom (ESDOF) models are widely used to evaluate the collapse capacity of multistory structures, and their rationality is very important because it greatly affects the accuracy of the evaluation results. Prior studies have indicated that obvious cyclic deterioration (CD) behaviors exist before structural collapse, and such deterioration behaviors are the primary sources of collapse for reinforced concrete (RC) frames subjected to long-duration ground motions. Although several ESDOF models have been developed to represent the global mechanical behaviors during the collapse of RC frames, such models cannot reasonably consider CD behaviors. This paper establishes an ESDOF model capable of considering CD behaviors by utilizing the Ibarra-Krawinkler (I-K) model. The ESDOF model includes a monotonic backbone curve with a negative tangent stiffness and a hysteretic rule to consider CD behaviors based on hysteretic energy dissipation. A simple method utilizing the empirical relationship between the monotonic ductility capacity and hysteretic energy dissipation capacity of RC columns to determine the hysteretic energy dissipation capacity of the ESDOF model is proposed. The CD behaviors are simulated by calculating the hysteretic energy dissipation capacity of the ESDOF model using the empirical relationship, which is obtained by the regression analysis of the existing experimental data of the RC column tests. The proposed ESDOF model is validated by pseudo-static collapse experiments and collapse fragility analyses. The results demonstrate that CD behaviors cannot be ignored when performing the collapse analyses of RC frames and that the proposed ESDOF model can adequately predict the collapse capacity of RC frames. [ABSTRACT FROM AUTHOR]

Artificial pancreas (AP) is an important treatment for patients with Type 1 diabetes (T1D). The control algorithm adopted in an AP system determines its reliability and accuracy. The generalized predictive control (GPC) is a representative adaptive control algorithm and has been widely applied to AP systems. However, we found that the traditional GPC controller does not work well for adolescents with T1D because of their high‐fluctuating blood glucose and high insulin resistance. Here, we propose an improved GPC algorithm with an adaptive reference glucose trajectory and an adaptive softening factor. The slopes of the reference trajectory and the value of softening factor are calculated real‐time on the basis of the blood glucose concentration (BGC) variations. In silico testing was done using the US Food and Drug Administration (FDA) approved virtual patient software T1D mellitus. The BGC trace and density of 20 patient‐subjects (10 adults and 10 adolescents) were recorded. Results showed that the average BGC percentage within the target regions (70–180 mg/dL) of the tests with adaptive reference glucose trajectory and softening factor for adolescents (0.93 ± 0.07) was significantly higher than that of the traditional GPC algorithm tests (0.88 ± 0.11), suggesting that the control quality of the blood glucose of adolescents is significantly improved with our GPC algorithm. Therefore, our improved GPC controller is effective and should have a good applicability in AP systems. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes lacking of effective treatments. Enhanced excitability of dorsal root ganglion (DRG) neuron plays a crucial role in the progression of diabetic neuropathic hyperalgesia. Brain-derived neurotrophic factor (BDNF) is known as a neuromodulator of nociception, but whether and how BDNF modulates the excitability of DRG neurons in the development of DPN remain to be clarified. This study investigated the role of exogenous BDNF and its high-affinity tropomyosin receptor kinase B (TrkB) in rats with streptozotocin-induced diabetic neuropathic pain. The results showed that continued intrathecal administration of BDNF to diabetic rats dramatically alleviated mechanical and thermal hyperalgesia, as well as inhibited hyperexcitability of DRG neurons. These effects were blocked by pretreatment with TrkB Fc (a synthetic fusion protein consisting of the extracellular ligand-binding domain of the TrkB receptor). The expression of BDNF and TrkB was upregulated in the DRG of diabetic rats. Intrathecal administration of BDNF did not affect this upregulation. These data provide novel information that exogenous BDNF relieved pain symptoms of diabetic rats by reducing hyperexcitability of DRG neurons and might be the potential treatment of painful diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Objective To explore whether the downregulation of protein phosphatase 2A catalytic subunit(PP2Ac)involved in the pathogenesis of mitochondria fission/fusion dynamics and functional imbalance induced by human tau accumulation. Methods After cotransfection with mito-dsRed plasmids and pIRES-eGFP-tau40 plasmids 48 hours,the rat primary hippocampal neurons were observed with a laser scanning confocal microscope for their changes in shape and distribution of mitochondria.The expressions of mitochondria fission/fusion protein and PP2Ac and PP2Ab were detected by Western blotting.Furthermore,the shape and distribution of mitochondria of rat primary hippocampal neuron and wild type 293wt cells were assayed 48 hours after co-transfection with siPP2Ac-EGFP plasmids and mito-DsRed plasmids,and the fission/fusion dynamics of 293wt cells was captured with live cell time-lapse imaging after co-transfection with siPP2Ac plasmids and mito-Dendra2 plasmids.After transfection with siPP2Ac plasmids,the relative level of mitochondria fission/fusion protein of 293wt cells was assayed by Western blotting,and mitochondria membrane potential was detected by JC-1 staining,and the cellular viability was measured by CCK8 assay.Finally,the shape and distribution and membrane potential of mitochondria of HEK293 cells with stable transfection of htau40(293htau)were detected after co-transfection with PP2Ac and mito-dsRed plasmids. Results Human tau40 expression decreased distribution of mitochondria and significantly lowered PP2Ac level in primary hippocampal neuron( t =4.814, P =0.0086).Down-regulation of PP2Ac caused mitochondria elongation and perinuclear accumulation in primary hippocampal neuron and 293wt cells;in addition,down-regulation of PP2Ac in 293wt cells significantly increased mitochondria fusion rate( t =2.857, P =0.0074)and the levels of mitochondria fusion protein mitofusin(MFN)1( t =6.768, P =0.0025),MFN2( t =3.121, P =0.0035),and optic atrophy 1( t =3.775, P =0.0199);however,the levels of dynamin-like protein-1 and Fis1 remained unchanged.The down-regulation of PP2Ac in 293wt cells led to the significant decrease in mitochondria membrane potential( t =2.300, P =0.0270)and cell viability( t =6.249, P <0.0001).Finally,up-regulation of PP2Ac attenuated the abnormalities in the shape,distribution and function of mitochondria in the 293htau cells. Conclusion Down-regulation of PP2Ac is involved in the abnormal shape and distribution of mitochondria and its dysfunction induced by human tau40 in rat primary hippocampal neurons and HEK293 cells.

One of the major pathological characteristics of Alzheimer's disease (AD) is the presence of enhanced deposits of beta-amyloid peptide (Aβ). The neuropeptide galanin (GAL) and its receptors are overexpressed in degenerating brain regions in AD. The functional consequences of galaninergic systems plasticity in AD are unclear. The objective of the present study was to investigate whether exogenous galanin could attenuate spatial memory impairment and hippocampal Aβ aggregation in rat model of AD. The effects of Aβ, galanin, galanin receptor 1 agonist M617 and galanin receptor 2 agonist AR-M1896 on spatial memory were tested by Morris water maze. The effects of Aβ, galanin, M617 and AR-M1896 on hippocampal Aβ protein expression were evaluated by western blot assay. The expression of galanin, galanin receptors 1 and 2 in rats' hippocampus were detected by real time PCR and western blot assay. The results showed that (1) Galanin administration was effective in improving the spatial memory and decreasing hippocampal Aβ levels after intracerebroventricular injection of Aβ; (2) AR-M1896 rather than M617 could imitate these effects of galanin; (3) GAL and GALR2 mRNA and protein levels increased significantly in hippocampus after Aβ administration, while GALR1 mRNA and protein levels did not change; (4) GAL, AR-M1896 and M617 administration did not show significant effect on GAL, GalR1 and GalR2 mRNA and protein levels in hippocampus after Aβ administration. These results implied that galanin receptor 2, but not receptor 1 was involved in the protective effects against spatial memory impairment and hippocampal Aβ aggregation.