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The article presents a novel strategy for enhancing the efficiency of machines that are used for complex structure machining. It proposes a low-cost five-axis four-linkage milling system as an alternative to the more expensive five-axis five-linkage system. Kinematic analysis of the machine tool is conducted to establish a correlation between the tool location data and the displacement of kinematic axes. An interpolation algorithm is then devised to determine a four-axis linkage milling strategy. The theoretical errors of the interpolation trajectory are observed to be reduced following the transformation. The research employs impeller processing as a case study, wherein the five-axis linkage machining path is translated into a more efficient five-axis four-linkage path using the interpolation algorithm. The practical application of this novel milling strategy confirms its effectiveness in processing the integral impeller within acceptable efficiency parameters. The results provide a theoretical foundation for the practical application of the low-cost five-axis four-linkage machining strategy in high-precision five-axis five-linkage machine tools. [ABSTRACT FROM AUTHOR]

Adenovirus-mediated expression of hypoxia-inducible factor 1 α double mutant (pAd-HIF-1 α-Ala564-Ala803) can be effectively transfected into bone marrow stem cells (MSCs) in the MSCs and cardiomyocytes co-culture system at normoxia to regulate the expression of downstream target genes of hypoxia-inducible factor 1 α (HIF-1 α), which in turn can promote MSC differentiation into cardiomyocytes. Fibroblasts share common characteristics with MSCs such as the morphology, phenotype and differentiation potential. Therefore, we further studied whether the pAd-HIF-1 α-Ala564-Ala803 also can convert neonatal rat cardiac fibroblasts (NCFs) into (cardio)myocyte phenotype via regulating the downstream target genes of HIF-1α at normoxia. The immunostaining analysis showed that NCFs treated with pAd-HIF-1 α-Ala564-Ala803 exhibited higher protein expression levels of smooth muscle α-actin (SMA, myocyte marker) and cardiac troponin T (cTnT, cardiomyocyte marker), compared with phosphate-buffered saline and pAd-LacZ treatments. The reverse transcription-polymerase chain reaction results showed that NCFs transfected with pAd-HIF-1 α-Ala564-Ala803 augmented messenger RNA (mRNA) expression of transforming growth factor- β1 (TGF- β1), Smad4, NKx2.5, GATA4, myocardin, SMA and cTnT. The effects of HIF-1 α-Ala564-Ala803 on NCFs were attenuated by pre-transfection of TGF- β1 or myocardin small interference RNAs. Adult CFs transfected with pAd-HIF-1 α-Ala564-Ala803 showed a lower protein expression of SMA but not cTnT without any change in the mRNA expression level of NKx2.5, myocardin. Therefore, NCFs but not adult CFs possess a similar differentiation potential to MSCs as evidenced by the fact that pAd-HIF-1 α-Ala564-Ala803 can convert NCFs into (cardio)myocyte phenotype via regulating its downstream target genes. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Bone marrow derived stromal cells (MSCs) can prevent the apoptosis of ischemic cardiomyocytes (CMCs). This anti-apoptosis activity may be related to an activation of the HIF-1α signal pathway in MSCs. Therefore, we investigated protective effects of an adenovirus (Ad)-mediated active form of HIF-1α (HIF-1α-Ala564-Ala803) modified MSCs on CMCs against CoCl2-induced apoptosis. At normoxia, pAd-HIF1α-Ala564-Ala803 exhibited a stable HIF-1α protein expression in MSCs. Compared with the single CMC culture, the TGF-β1 level and the Bcl-2 expression were significantly increased, concomitant with a reduced expression of caspase-3, the LDH release and TUNEL-positive CMCs in CMC and MSC, β-galactosidase (LacZ)-MSC or HIF-1α-Ala564-Ala803-MSC coculture exposed to CoCl2. Furthermore, these effects were more prominent in CMC and HIF-1α-Ala564-Ala803-MSC coculture than in CMC and MSC or LacZ-MSC coculture exposed to CoCl2. Pre-transfection of TGF-β1-small interfering RNA (siRNA) effectively inhibited the TGF-β1 level, resulting in a dramatic reduction in the Bcl-2 expression as well as an increased level of apoptosis in CMC and HIF-1α-Ala564-Ala803-MSC coculture exposure to CoCl2, whereas pre-transfection of green fluorescent protein (GFP)-siRNA had no such effects. These data suggest that HIF1α-Ala564-Ala803 modified MSCs have better protective effects of CMCs against the CoCl2-induced apoptosis and these protective effects are at least partly TGF-β1-mediated. [Copyright &y& Elsevier]

Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H 2 S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H 2 S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT 1 R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H 2 O 2 ) incubation, and these H 2 O 2 -induced alterations were reversed by diphenyleneiodonium, apocynin and H 2 S supplementation. Flow cytometry and Western blotting revealed that blockade of H 2 S biosynthesis using dl -propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H 2 S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H 2 S supplementation and losartan (an AT 1 R blocker) pretreatment. In conclusion, our study indicates that H 2 S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H 2 S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression. [ABSTRACT FROM AUTHOR]