The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.
Pigs are animals that live in groups and have social hierarchies within the group. After mixing, they can re-establish social hierarchies within several days through fighting. Dominance hierarchical indices, such as I&SI, Elo rating, and Glicko rating, have been used to analyze social hierarchies of some social animals but not pigs. I&SI index involves iterative calculations that first minimize the number of inconsistencies (I) in a dominance matrix, and then minimize the strength of those inconsistencies (SI). Elo rating and Glicko rating indices are based on the sequence in which interactions occur, and continuously update ratings by looking at interactions sequentially. To study the temporal dynamics of social hierarchy formation and maintenance in weaned pigs after mixing, a total of 102 pigs (47 females and 55 barrows) were selected by similar body weight and mixed in 10 pens (10 or 11 females or barrows per pen). Their behavior was recorded and observed for 72 h after mixing. Results showed that hierarchical indices I&SI, Elo rating, and Glicko rating were associated with each other (|r| = 0.681 ~ 0.942, p < 0.001). I&SI was associated with logarithms of frequency of active attack (|r| = 0.65, p < 0.05) and tended to associated with logarithms of frequency of standoff (|r| = 0.48, p < 0.1). Elo rating, and Glicko rating were associated with the logarithms of duration of being bullied (|r| = 0.393~0.401, p < 0.05). In addition, Glicko rating tended to be associated with the logarithms of duration of active attack and frequency of active attack (|r| = 0.416~0.439, p < 0.1). Multiple linear regression analyses of logarithms of dyadic behavior indicators for three hierarchical indices indicated the same effects. The time (hours) to achieve social stability of pigs after mixing was lower for females than barrows (23.06 ± 4.15 vs. 40.55 ± 4.71 h; p < 0.001). The most dominant pig (the first ranked) in each pen quickly appeared within a few hours after mixing and remained stable. Overall, our study demonstrated that the ranks calculated by the three dominance hierarchical indices: I&SI, Elo rating, and Glicko rating, were consistent and partially associated with part of the dyadic behavioral indicators in weaned pigs after mixing.
High-mobility group box 2 (HMGB2) is an abundant, chromatin-associated protein that plays an essential role in the regulation of transcription, cell proliferation, differentiation, and tumorigenesis. However, the underlying mechanism of HMGB2 in adipogenesis remains poorly known. Here, we provide evidence that HMGB2 deficiency in preadipocytes impedes adipogenesis, while overexpression of HMGB2 increases the potential for adipogenic differentiation. Besides, depletion of HMGB2 in vivo caused the decrease in body weight, white adipose tissue (WAT) mass, and adipocyte size. Consistently, the stromal vascular fraction (SVF) of adipose tissue derived from hmgb2−/− mice presented impaired adipogenesis. When hmgb2−/− mice were fed with high-fat diet (HFD), the body size, and WAT mass were increased, but at a lower rate. Mechanistically, HMGB2 mediates adipogenesis via enhancing expression of C/EBPβ by binding to its promoter at “GGGTCTCAC” specifically during mitotic clonal expansion (MCE) stage, and exogenous expression of C/EBPβ can rescue adipogenic abilities of preadipocytes in response to HMGB2 inhibition. In general, our findings provide a novel mechanism of HMGB2-C/EBPβ axis in adipogenesis and a potential therapeutic target for obesity.
An approach for designing the compliant adaptive wing leading edge with composite material is proposed based on the topology optimization. Firstly, an equivalent constitutive relationship of laminated glass fiber reinforced epoxy composite plates has been built based on the symmetric laminated plate theory. Then, an optimization objective function of compliant adaptive wing leading edge was used to minimize the least square error (LSE) between deformed curve and desired aerodynamics shape. After that, the topology structures of wing leading edge of different glass fiber ply-orientations were obtained by using the solid isotropic material with penalization (SIMP) model and sensitivity filtering technique. The desired aerodynamics shape of compliant adaptive wing leading edge was obtained based on the proposed approach. The topology structures of wing leading edge depend on the glass fiber ply-orientation. Finally, the corresponding morphing experiment of compliant wing leading edge with composite materials was implemented, which verified the morphing capability of topology structure and illustrated the feasibility for designing compliant wing leading edge. The present paper lays the basis of ply-orientation optimization for compliant adaptive wing leading edge in unmanned aerial vehicle (UAV) field. ª 2014 Production and hosting by Elsevier Ltd. on behalf of CSAA & BUAA.
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