Wire arc additive manufacturing (WAAM) technique has revealed the potential of replacing existing aerospace industry parts manufactured by traditional manufacturing routes. The reduced mechanical properties compared to wrought products, the porosity formation, and solidification cracking are the prime constraints that are restricting wide-spread applications of WAAM products using aluminium alloys. An interpass temperature is less studied in robotic WAAM and is the vital aspect affecting the properties of a formed product. This paper highlights the effects of change in interpass temperature on porosity content and mechanical properties of WAAM parts prepared using DC pulsed GMAW process, with 5356 aluminium consumable wire. The samples prepared with different interpass temperatures were studied for the distribution of pores with the help of computed tomography radiography (CT radiography) technique. A WAAM sample produced with higher interpass temperature revealed 10.41% less porosity than the sample prepared with lower interpass temperature. The pores with size less than 0.15mm3 were contributing over 95% of the overall porosity content. Additionally, on a volumetric scale, small pores (<0.15mm3) in the higher interpass temperature sample contributed 81.47% of overall volume of pores whereas only 67.92% volume was occupied in lower interpass temperature sample with same sized pores. The different solidification rates believed to have influence on the hydrogen evolution mechanism. Tensile properties of higher interpass temperature sample were comparatively better than lower interpass temperature sample. For the deposition pattern used in this study, horizontal specimens were superior to vertical specimens in tensile properties.
Background: Increased risk and cancer-related mortality is observed in pancreatic cancer (PC) patients with diabetes mellitus (DM). Whether using metformin as glucose-lowering therapy can result in survival benefit in this group of patients is still unclear. Methods: A meta-analysis of 21 studies that including 38,772 patients was performed to investigate the association between metformin and overall survival in patients with PC and concurrent DM. Results: A significant survival benefit was observed in metformin treatment group compared with non-metformin group (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.74–0.91). These associations were observed in both subgroups of Asian countries (HR = 0.69, 95% CI: 0.60–0.79) and Western countries (HR = 0.86, 95% CI: 0.76–0.95), the former was more obvious. Survival benefit was gained for patients at early stage (HR = 0.75, 95% CI: 0.64–0.85) and mixed stage (HR = 0.81, 95% CI: 0.70–0.91), but not for patients at advanced stage (HR = 0.99, 95% CI: 0.74–1.24). Similarly, survival benefit was also observed in patients receiving surgery (HR = 0.82, 95% CI: 0.69–0.94) and comprehensive treatment (HR = 0.85, 95% CI: 0.77–0.93), but not in chemotherapy group (HR = 0.99, 95% CI: 0.67–1.30). No obvious benefit was suggested when pooled by time-varying COX model (HR = 0.94, 95% CI: 0.86–1.03). Conclusions: These results suggest that metformin is associated with survival benefit in patients with PC and concurrent DM. Further randomized controlled trials and prospective studies with larger sample sizes are required to confirm our findings.
Objective: It is unclear whether uterine fibroids are associated with the occurrence of hypertensive disorders of pregnancy (HDP). Thus, this study aimed to evaluate the association between uterine fibroids and HDP in a prospective cohort. Methods: Overall, 2404 pregnant women who received antenatal care were enrolled in a prospective cohort in China between 2014 and 2016; 2277 women met the inclusion criteria of this study. The clinical characteristics of participants were assessed via questionnaires and physical examinations at baseline (before the 20th week of gestation), 21st–27th, 28th–34th, and 35th–39th gestational weeks. Ultrasound examination was performed before the 20th week of pregnancy to determine the presence of uterine fibroids. Linear mixed-effect and Cox proportional hazard regression models were used to analyze the association of uterine fibroids with blood pressure and HDP. Results: Of 2277 pregnant women, 242 (10.6%) had uterine fibroids, and 45 (2.0%) subsequently developed HDP. The incidence of HDP in women with and without uterine fibroids was 5% ( n = 12) and 1.6% ( n = 33), respectively. The longitudinal SBPs and DBPs were significantly higher in women with uterine fibroids than in those without. The multivariable Cox model showed that the presence of uterine fibroids was associated with increased HDP risk (adjusted hazard radio: 2.95, 95% confidence interval: 1.35–6.44). Conclusion: Uterine fibroids in early pregnancy were associated with an increased HDP risk. Blood pressure of women with uterine fibroids should be closely monitored, and HDP preventive measures are crucial.
Mesenchymal stem cells (MSCs) can differentiate into neuronal-like cell types under specific conditions. The classical antioxidant inducers such as β-mercaptoethanol (BME), butylated hydroxyanisol (BHA), and dimethylsulfoxide (DMSO) are limited in clinical because of toxicity. Resveratrol, a safer, natural antioxidant, can stimulate osteoblastic differentiation of MSCs. However, its effect of inducing MSCs to differentiate into neuronal-like cells is less well studied, and its differentiated mechanisms are not well understood. Sonic hedgehog (Shh) signaling, mediated by the primary cilia, is crucial for embryonic development and tissue differentiation, but relatively little is known about the role of Shh signaling and primary cilia in neuronal-like differentiation of MSCs. Here we show that primary cilia, harboring patched 1 (Ptc1), are present in growth-arrested MSCs and that smoothened (Smo) and Gli1 are present in cytoplasm of MSCs, which are important components of the Shh signaling pathway. After resveratrol induction, MSCs acquire neuronal-like cell morphologies and phenotypes, Smo translocates to the primary cilia, Gli1 enters the nucleus, and expressions of Smo and Gli1 proteins increase, which can be inhibited by cyclopamine, a Smo antagonist. Meanwhile, Smo agonist (SAG) attains similar effects compared with the resveratrol group. These data indicate that resveratrol can induce MSCs to differentiate into neuronal-like cells and activate Shh signaling pathway in the primary cilia. Moreover, the primary cilia and Shh signaling are essential for resveratrol inducing neuronal-like differentiation of MSCs. Our finding is important for understanding the neuronal-like differentiation mechanism of MSCs for resveratrol and promoting its clinical therapeutic utility.
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