Crack propagation and strain-induced α’-martensite transformation in selective laser melting 316L stainless steels

At present, in-situ monitoring of metal cracking and propagation is still a challenge. In this work, we used in-situ tensile tests with precast cracks of selective laser melting (SLM) and conventionally manufactured (CM) 316L stainless steels (SSs) to study crack propagation and strain-induced α′-martensite transformation. During in-situ tensile, cracks initiate at the concentration of slip lines at the precast crack, and the strong stress at the crack tip will tear apart the grain boundaries causing the crack to propagate until the samples are completely fractured. After in-situ tensile, abnormal grain growth was observed in the plastic zone at the crack tip of the SLMed 316L SS sample, while austenite to α′-martensite transformation was appeared at the grain boundaries of the SLMed 316L SS sample, and martensitic patches generated by severe plastic deformation induced in the CM 316L SS were also observed. The SLMed 316L SS shows higher strength and resistance to deformation than CM 316L SS. In addition, the stress concentration at the crack tip in crack propagation has a significant effect on the transformation of strain-induced α′-martensite

Astragalin Promotes Osteoblastic Differentiation in MC3T3-E1 Cells and Bone Formation in vivo

Astragalin (AG) is a biologically active flavonoid compound that can be extracted from a number of medicinal plants. However, the effects of AG on osteoblastic differentiation in mouse MC3T3-E1 cells and on bone formation in vivo have not been studied fully. In this study, we found that the activities of alkaline phosphatase (ALP) and mineralized nodules in MC3T3-E1 cells were both significantly increased after treatment with AG (5, 10, and 20 μM). Meanwhile, the mRNA and protein levels of osteoblastic marker genes in MC3T3-E1 cells after AG treatment were markedly increased compared with a control group. In addition, the levels of BMP-2, p-Smad1/5/9, and Runx2 were significantly elevated in AG-treated MC3T3-E1 cells. Moreover, we found that the protein levels of Erk1/2, p-Erk1/2, p38, p-p38, and p-JNK were also significantly increased in AG-treated MC3T3-E1 cells compared to those in the control group. Finally, in vivo experiments demonstrated that AG significantly promoted bone formation in an ovariectomized (OVX)-induced osteoporotic mouse model. This was evidenced by significant increases in the values of osteoblast-related parameters (BFR/BS, MAR, Ob.S/BS, and Ob.N/B.Pm) and bone histomorphometric parameters (BMD, BV/TV, Tb.Th, and Tb.N.) in OVX mice after AG treatment (5, 10, and 20 mg/kg). Collectively, these results demonstrated that AG may promote osteoblastic differentiation in MC3T3-E1 cells via the activation of the BMP and MAPK pathways and promote bone formation in vivo. These novel findings indicated that AG may be a useful bone anabolic agent for the prevention and treatment of osteoporosis

Four-Level Micro-Via Technology (4LµV) for ASIC Integration in Active Flexible Sensor Arrays

Systems-in-foil with multi-sensor arrays require extensive wiring with large numbers of data lines. This prevents scalability of the arrays and thus limits the applications. To enable multiplexing and thus reducing the external connections down to few digital data links and a power supply, active circuits in the form of ASICs must be integrated into the foils. However, this requires reliable multilayer wiring of the sensors and contacts for chip integration. As an elegant solution to this, a new manufacturing process for multilayer wiring in polyimide-based sensor foils has been developed that also allows ASIC chips to be soldered. The electrical four-level micro-via connections and the contact pads are generated by galvanic copper deposition after all other process steps, including stacking and curing of polyimide layers, are completed. Compared to layer by layer via technology, the processing time is considerably reduced. Because copper plating of vias and solderable copper contact pads happens as the final step, the risk of copper oxidation during polyimide curing is completely eliminated. The entire fabrication process is demonstrated for six strain sensor nodes connected to a surface-mounted ASIC as a detecting unit for sensing spatially resolved bending states. Each sensor node is a full-bridge configuration consisting of four strain gauges distributed across interconnected layers. The sensor foil allows bending of +/-120° without damage. This technology can be used in future for all kinds of complex flexible systems-in-foil, in particular for large arrays of sensors

Bifunctional enzyme ATIC promotes propagation of hepatocellular carcinoma by regulating AMPK-mTOR-S6 K1 signaling

Abstract Background Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. To effectively treat HCC, new molecular targets and therapeutic approaches must be identified. 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate (IMP) cyclohydrolase (ATIC), a bifunctional protein enzyme, catalyzes the last two steps of the de novo purine biosynthetic pathway. Whether ATIC contributes to cancer development remains unclear. Methods ATIC mRNA levels in different types of human HCC samples or normal tissues were determined from Gene Expression across Normal and Tumor tissue (GENT) database. The expression level of ATIC in human HCC samples or cell lines were examined by RT-PCR and western blot. Overall survival and disease-free survival of HCC patients in the ATIC low and ATIC high groups were determined by Kaplan-Meier analysis. Effects of ATIC knockdown by lentivirus infection were evaluated on cell-proliferation, cell-apoptosis, colony formation and migration. The mechanisms involved in HCC cells growth, apoptosis and migration were analyzed by western blot and Compound C (C-C) rescue assays. Results Here, we first demonstrated that expression of ATIC is aberrantly up-regulated in HCC tissues and high level of ATIC is correlated with poor survival in HCC patients. Knockdown of ATIC expression resulted in a dramatic decrease in proliferation, colony formation and migration of HCC cells. We also identified ATIC as a novel regulator of adenosine monophosphate-activated protein kinase (AMPK) and its downstream signaling mammalian target of rapamycin (mTOR). ATIC suppresses AMPK activation, thus activates mTOR-S6 K1-S6 signaling and supports growth and motility activity of HCC cells. Conclusion Taken together, our results indicate that ATIC acts as an oncogenic gene that promotes survival, proliferation and migration by targeting AMPK-mTOR-S6 K1 signaling

VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via activation of AKT-dependent ROS production in NSCLC

Previous studies have confirmed that protein tyrosine phosphatase 1B (PTP1B) can promote tumour progression in non-small cell lung cancer (NSCLC). Vanadyl alginate oligosaccharides (VAOS) is a new coordination compounds that possesses a good PTP1B inhibitory activity. However, the potent anticancer efficacy of VAOS in human NSCLC requires further study. In this study, VAOS exhibited effective inhibitory effects in NSCLC both in cultured cells and in a xenograft mouse model. VAOS was further identified to induce NSCLC cell apoptosis through activating protein kinase B (AKT) to elevate intracellular reactive oxygen species (ROS) levels by increasing in oxygen consumption and impairing the ROS-scavenging system. Neither silencing of PTP1B by siRNA nor transient overexpression of PTP1B had an effect on the AKT phosphorylation triggered by VAOS, indicating that PTP1B inhibition was not involved in VAOS-induced apoptosis. Through phosphorus colorimetric assay, we demonstrated that VAOS notably inhibited phosphatase and tensin homologue deleted on chromosome 10 (PTEN) dephosphorylation activity, another member of the protein tyrosine phosphatases (PTPases)-upstream factor of AKT. Interestingly, PTEN knockdown sensitized cells to VAOS, whereas ectopic expression of PTEN markedly rescued VAOS-mediated lethality. In vivo, VAOS treatment markedly reduced PTEN activity and tumour cell burden with low systemic toxicity. Thus, our data not only provided a new therapeutic drug candidate for NSCLC, but presented new understanding into the pharmacological research of VAOS

Additional file 1: of Bifunctional enzyme ATIC promotes propagation of hepatocellular carcinoma by regulating AMPK-mTOR-S6Â K1 signaling

Supplementary Materials. (DOCX 818 kb

Circular RNA encoded MET variant promotes glioblastoma tumorigenesis

Abstract Activated by its single ligand, hepatocyte growth factor (HGF), the receptor tyrosine kinase MET is pivotal in promoting glioblastoma (GBM) stem cell self-renewal, invasiveness and tumorigenicity. Nevertheless, HGF/MET-targeted therapy has shown limited clinical benefits in GBM patients, suggesting hidden mechanisms of MET signalling in GBM. Here, we show that circular MET RNA (circMET) encodes a 404-amino-acid MET variant (MET404) facilitated by the N6-methyladenosine (m6A) reader YTHDF2. Genetic ablation of circMET inhibits MET404 expression in mice and attenuates MET signalling. Conversely, MET404 knock-in (KI) plus P53 knock-out (KO) in mouse astrocytes initiates GBM tumorigenesis and shortens the overall survival. MET404 directly interacts with the MET β subunit and forms a constitutively activated MET receptor whose activity does not require HGF stimulation. High MET404 expression predicts poor prognosis in GBM patients, indicating its clinical relevance. Targeting MET404 through a neutralizing antibody or genetic ablation reduces GBM tumorigenicity in vitro and in vivo, and combinatorial benefits are obtained with the addition of a traditional MET inhibitor. Overall, we identify a MET variant that promotes GBM tumorigenicity, offering a potential therapeutic strategy for GBM patients, especially those with MET hyperactivation