Background: Type 2 diabetes mellitus (T2DM) is a major cause of death with an increasing incidence at an epidemic rate. The existing treatments for T2DM lack long-term effective blood glucose control. In this study, the effects of miR-21 antagomir on T2DM and the related mechanism were investigated using streptozotocin (STZ)-induced T2DM rats.Methods: 30 T2DM rats were randomly divided into 3 groups (n=10): T2DM group, T2DM rats with miR-21 antagomir group, T2DM rats with NC antagomir group. The expression of miR-21 in rats was detected by qRT-PCR. blood glucose, triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-Cho), insulin, adiponectin, ITT and GTT were detected. The expression of TIMP3 in si-TIMP3 rats and the expression of TIMP3 in T2DM rats with miR-21 antagomir and si-TIMP3 was detected by Western blotting.Results: We found that miR-21 antagomir reduced blood glucose concentration in T2DM rats. MiR-21 antagomir improved lipid metabolic disorder by decreasing the levels of triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-Cho) and increasing the level of high-density lipoprotein cholesterol (HDL-Cho). Also, miR-21 antagomir reduced the value of homeostasis model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (HbAc1), plasma insulin, and up-regulated the plasma adiponectin. These results, combined with insulin tolerance tests (ITT) and glucose tolerance tests (GTT) results, showed that miR-21 improved insulin resistance in STZ-induced T2DM rats. Then the target relationship between miR-21 and tissue inhibitor of metalloproteinases 3 (TIMP3) was proved by luciferase reporter assay. More impressively, miR-21 significantly increased the expression level of TIMP3 in STZ-induced T2DM rats. Conclusion:Our study taken together has shown that miR-21 antagomir improved insulin resistance and lipid metabolism disorder in STZ-induced T2DM rats by up-regulating the expression level of TIMP3. This study suggested that miR-21 antagomir could be used as an effective therapeutic strategy and the underlying mechanism was revealed.

Introduction: Ti6Al4V titanium alloy is widely used in producing orthopedic and maxillofacial implants, but drawbacks include high elastic modulus, poor osseointegration performance, and toxic elements. A new medical titanium alloy material with better comprehensive performance is urgently needed in the clinic.Methods: Ti10Mo6Zr4Sn3Nb titanium alloy (referred to as Ti-B12) is a unique medical ß titanium alloy material developed by us. The mechanical properties of Ti-B12 depict that it has advantages, such as high strength, low elastic modulus, and fatigue resistance. In our study, the biocompatibility and osseointegration properties of Ti-B12 titanium alloy are further studied to provide theoretical guidance for its clinical transformation.Results and Discussion: The titanium alloy Ti-B12 displays no significant effect on MC3T3-E1 cell morphology, proliferation, or apoptosis in vitro. Neither Ti-B12 titanium alloy nor Ti6Al4V titanium alloy depicts a significant difference (p > 0.05); Ti-B12 material extract injected into the abdominal cavity of mice does not cause acute systemic toxicity. The skin irritation test and intradermal irritation test reveal that Ti-B12 does not cause skin allergic reactions in rabbits. Compared to Ti6Al4V, Ti-B12 titanium alloy material has more advantages in promoting osteoblast adhesion and ALP secretion (p < 0.05). Although there is no significant difference in OCN and Runx2 gene expression between the three groups on the 7th and 14th days of differentiation induction (p > 0.05), the expression of Ti-B12 group is higher than that of Ti6Al4V group and blank control group. Furthermore, the rabbit in vivo test present that 3 months after the material is implanted in the lateral epicondyle of the rabbit femur, the Ti-B12 material fuses with the surrounding bone without connective tissue wrapping. This study confirms that the new β-titanium alloy Ti-B12 not only has low toxicity and does not cause rejection reaction but also has better osseointegration performance than the traditional titanium alloy Ti6Al4V. Therefore, Ti-B12 material is expected to be further promoted in clinical practice.

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A better understanding of how streamflow interacts with climate change and human activities would contribute to the efficiency and effectiveness of water resources management. Specifically, quantifying the climate and human contributions has widely been used when attributing streamflow changes. However, only a few previous studies compared the results derived by different methods that are currently available, and even fewer studies have ever had a close look at the uncertainties induced by various estimations of evapotranspiration. This research first examined the streamflow changes for 12 catchments on the Loess Plateau in China during the period of 1961–2018 with Mann–Kendall test and relevant statistical measurements. Then, 8 Budyko-based climate elasticity methods, each with 13 estimations of evapotranspiration, were used to quantifying human and climate contributions to streamflow change in the study area (i.e., 104 pairs of values for human and climate contributions for one catchment). The results showed that significant declining trends could be found in 11 of the 12 catchments studied. In terms of contribution rates, human activity has been shown as the major contributor to the streamflow decrease (60–90%) compared to climate change (10–50%). By comparing the contribution results derived by possible combinations of attribution method and evapotranspiration estimation, the variability due to different Budyko-based methods being used seems to be related to geographical location and climate. Although the spatial pattern of variability due to different estimations of evapotranspiration is not obvious, it is necessary to consider the uncertainties induced when launching contribution analysis over specific regions.

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