控制薄壁细长径零件淬火变形的工艺措施

从某产品零件淬火变形原因分析出发,较详细地讨论了此类产品淬火变形机理和控制变形的具体方法,取得了理想的效果。

变径细长轴类零件的旋风铣削方法研究

提出了一种用旋风铣削代替车削加工变径细长工件的加工方法。介绍了该方法的加工原理和刀具与工件的相对运动关系,设计了数控变径旋风铣床。此加工方法可以有效地提高变径细长工件的径向尺寸精度、表面质量及生产效率,减小工件表面的形状误差,具有广泛的工程意义。

Ginsenoside Rg_3 inhibit hepatocellular carcinoma growth via intrinsic apoptotic pathway

AIM:To investigate the anti-tumor function of ginsenoside Rg3 on hepatocellular carcinoma(HCC) in vitro and in vivo,and its mechanism.METHODS:Hep1-6 and HepG2 cells were treated by Rg3 in different concentrations(0,50,100 and 200 μg/mL) in vitro.After incubation for 0,6,12,24 and 48 h,cell viability was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay.Apoptosis was identified by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling.Caspase-3 activity was measured by chromophore p-nitroanilide and flow cytometry.Bcl-2 family proteins were ascertained by Western-blotting.Mitochondria membrane potentialwas detected by 5,5',6' 6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide.Forty liver tumor-bearing C57Bl6 mice were divided randomly into 4 groups for intra-tumor injection of saline,ginsenoside Rg3,cyclophosphamide(CTX) and ginsenoside Rg3 + CTX combination.RESULTS:The survival time was followed up to 102 d.The mice in the Rg3 + CTX group showed significant increased survival time compared with those in the control group(P < 0.05).Rg3 could inhibit HCC cell proliferation and induce cell apoptosis in vitro in the concentration and time dependent manner.It also induced mitochondria membrane potential to decrease.Caspase-3 activation can be blocked by the inhibitor z-DEVD-FMK.Bax was up-regulated while Bcl-2 and Bcl-XL were down-regulated after Rg3 treatment.CONCLUSION:Our data suggested that Rg3 alone or combined with CTX inhibited tumor growth in vivo and prolonged mouse survival time by inducing HCC cell apoptosis via intrinsic pathway by expression alterations of Bcl-2 family proteins.

Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer

AIM： To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma （HCC）. METHODS： Erlotinib-induced alterations in gene expression were evaluated using cDNA array technology; changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting. RESULTS： Erlotinib treatment inhibited the mitogen activated protein （MAP）-kinase pathway and signal transducer of activation and transcription （STAT）- mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cDNA array technology. Overexpression of proapoptotic factors like caspases and gadds associated with a down-regulation of antiapoptotic factors like Bcl-2, Bcl-XL or jun D accounted for erlotinib＇s potency to induce apoptosis. Downregulation of cell cycle regulators promoting the G1/S-transition and overexpression of cyclin-dependent kinase inhibitors and gadds contributed to the induction of a G1/G0-arrest in response to erlotinib. Furthermore, we displayed the transactivation of EGFR-mediated signaling by the IGF-1-receptor and showed erlotinib＇s inhibitory effects on the receptor-receptor cross talk. CONCLUSION： Our study sheds light on the understanding of the mechanisms of action of EGFR-TK- inhibition in HCC-cells and thus might facilitate the design of combination therapies that act additively or synergistically. Moreover, our data on the pathways responding to erlotinib treatment could be helpful in predicting the responsiveness of tumors to EGFR-TKIs in the future.

Targeting stem cell signaling pathways for drug discovery:advances in the Notch and Wnt pathways

Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.

Fatty acid metabolism and cancer development

Although the type and etiology of cancers are different, pathways in glucose metabolism, pentose phos- phate pathway （PPP） and glutamine metabolism have been reprogrammed in cancer cells to adapt to their rapid growth and proliferation. Recent research has also shown that mul- tiple lipid metabolic pathways are altered in cancer cells. Here, we provide a brief review for the role of fatty acid metabolism in cancer development with a special focus on fatty acid uptake and de novo synthesis, triglycerides syn- thesis, storage and degradation. Reprogramming in fatty acid metabolism plays important roles in providing energy, macromolecules for membrane synthesis and lipid signals during cancer development. Understanding the mechanism of deregulated lipid metabolic pathways in cancer cells would reveal novel therapeutic approaches to combat cancer.

Multi-Type Directed Scale-Free Percolation

In this paper,we study a long-range percolation model on the lattice Z d with multi-type vertices and directed edges.Each vertex x ∈ Z d is independently assigned a non-negative weight Wx and a type ψx,where(Wx) x∈Z d are i.i.d.random variables,and(ψx) x∈Z d are also i.i.d.Conditionally on weights and types,and given λ,α > 0,the edges are independent and the probability that there is a directed edge from x to y is given by pxy = 1 exp(λφψ x ψ y WxWy /| x-y | α),where φij 's are entries from a type matrix Φ.We show that,when the tail of the distribution of Wx is regularly varying with exponent τ-1,the tails of the out/in-degree distributions are both regularly varying with exponent γ = α(τ-1) /d.We formulate conditions under which there exist critical values λ WCC c ∈(0,∞) and λ SCC c ∈(0,∞) such that an infinite weak component and an infinite strong component emerge,respectively,when λ exceeds them.A phase transition is established for the shortest path lengths of directed and undirected edges in the infinite component at the point γ = 2,where the out/in-degrees switch from having finite to infinite variances.The random graph model studied here features some structures of multi-type vertices and directed edges which appear naturally in many real-world networks,such as the SNS networks and computer communication networks.