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Al alloys have widespread industrial applications. However, their mechanical strength is often much lower than steels. Here, we investigate the influence of solutes on achieving ultrahigh strength and thermal stability of nanotwinned Al alloys. In situ micropillar compression tests show the addition of a small amount of Ti can significantly increase the mechanical strength of Al-Ni alloys to 2 GPa. Deformation induced detwinning, Ni segregation and grain coarsening as discovered in binary Al-Ni alloys are mostly absent in the ternary Al-Ni-Ti alloys. Moreover, the ternary Al-Ni-Ti alloys have outstanding thermal stability. Density function theory calculations reveal the synergetic pinning effect of Ni-Ti solute pairs on incoherent twin boundaries. This study demonstrates that the proper selection of synergistic solute pairs is critical to improve the thermal stability and mechanical properties of nanotwinned Al alloys.

Gastric cancer is the most common gastrointestinal malignancy and the leading cause of cancer-related deaths in East Asia. Increasing evidence has revealed that autophagy is closely associated with tumor initiation and progression. The present work aimed to investigate the role of autophagy in adjuvant chemotherapy for gastric cancer.Gastric cancer stem cells (CSCs) were isolated from gastric cancer cell lines using the cell surface markers CD44 and CD54 and cultured in a three-dimensional cell culture system. Western blotting was used to detect their protein expression levels in gastric CSCs. In addition, the cells were treated with inhibitors to investigate the underlying mechanisms of autophagy.After isolation of gastric CSCs expressing CD44 and CD54, Western blot analysis showed that the levels of the autophagic marker LC3II were markedly enhanced in CD44+CD54+ gastric CSCs. Moreover, the ratio of LC3II/LC3I protein levels was higher in CD44+CD54+ gastric CSCs than in non-CSCs. By contrast, both a chemotherapeutic agent (5-fluorouracil) and autophagy inhibitor (chloroquine) exhibited an inhibitory effect on the cell viability of gastric CSCs, and their combination further enhanced such inhibitory effects. Mechanistically, the addition of Notch inhibitor decreased the cell viability of gastric CSCs treated with 5-fluorouracil and chloroquine. In addition, 5-fluorouracil and chloroquine both increased the expression of Notch1 in gastric CSCs.These findings show that autophagy regulated drug sensitivity of gastric cancer cells through the Notch signaling pathway.

Although the excimer laser, which utilizes 'non-thermal ablation effects', has achieved encouraging results in early clinical trials, the long-term results have failed to show any advantage over conventional percutaneous transluminal coronary angioplasty (PTCA).A new system, Smooth Excimer Laser Coronary Angioplasty (SELCA), has been developed to reduce the tissue damage in the vessel wall caused by shock waves and vapour bubbles.SELCA (wavelength 308 nm, pulse duration 115 ns, repetition rate 150 Hz and energy density 50 mJ mm(-2)) lowers the amount of shock wave formation and pressure peak amplitude in the surrounding tissue by about eight times when compared to the conventional 308 nm excimer laser (ELCA). In this preclinical evaluation, this new system was compared to ELCA. Fifty New Zealand White rabbits were stimulated by repeated weak DC impulses for a period of 28 days in order to form an atherosclerotic plaque in the right carotid artery. The vessels were excised 3, 7,14 and 28 days after laser irradiation for immunohistochemical analysis.SELCA and ELCA laser treatment lead to a decrease in maximal intimal wall thickness 3 days after intervention (control: 177+/-4 microm; SELCA: 131+/-22microm; ELCA: 120 +/-33microm). In the period between 3 and 28 days, a moderate increase in intimal wall thickness was observed after SELCA treatment compared to a significant increase after ELCA (28 days after intervention: SELCA: 157+/-22microm; ELCA: 274 +/-28microm). Bromodeoxyuridine (BrdU) was applied 18 and 12 h before excision of the vessels in order to determine the percent of cells undergoing DNA synthesis. The percent of BrdU labelled SMC in the intima (control: 13 +/- 2 cells mm(-2)) increased in both groups after 3 days (SELCA: 248 +/- 107 cells mm(-2); ELCA: 162 +/- 41 cells mm(-2)) and 7 days (SELCA: 162+/- 55 cells mm(-2); ELCA: 279 +/- 119 cells mm(-2)).The present results demonstrate that vascular wall injury and increase in intimal wall thickness following SELCA are reduced in comparison to the results achieved with the conventional technique. Further trials are necessary to assess whether these improvements will lead to more favourable long-term results after excimer laser angioplasty.

The aim of this study was to determine the vasomotor response to in vivo excimer laser irradiation with regard to laser-induced tissue effects. Transfemoral excimer laser angioplasty was performed in the right carotid artery of 11 New Zealand white rabbits. In four additional rabbits (sham group), the procedure was performed without the application of laser energy. Angiography documented vessel dissection in five laser-treated animals. Perforation occurred in one animal. Rings of the treated artery and controls of the contralateral artery were investigated in a contraction chamber. The passive stress-strain relation (PSS) and the maximum contraction force (MCF) after stimulation with noradrenaline, serotonin and potassium chloride were determined. The treated vessels had a higher PSS than the control (p=0.05). The MCF was lower in the treated vessels (p

To study the ablation effects induced by excimer laser coronary angioplasty (ELCA), we examined 41 segments of nine isolated coronary arteries. An electronic intracoronary ultrasound device (ICUS: 20 MHz, 3.5F, Endosonics) was positioned coaxially within the vessel. Angioplasty was performed using a 1.7 mm ELCA catheter (Spectranetics) which was placed in the lumen and directed vertically onto the intimal surface of the vessel (fluence: 10-50 mJ.mm-2). The laser catheter was removed after each lasing cycle to allow the stepwise evaluation of the morphological effects of ELCA and to avoid reaching the adventitia. Ultrasound images were compared with the corresponding histological specimens. In all cases, the ablation site could be correctly identified by ICUS. No penetration of the adventitia was seen at histology. Ablation depth was 0.31 +/- 0.18 mm as determined by histology and 0.34 +/- 0.18 mm as determined by ultrasound; the diameter of the crater was 0.63 +/- 0.21 mm, and 0.75 +/- 0.16 mm, respectively, and wall thickness was 0.68 +/- 0.18 mm, and 0.83 +/- 0.20 mm, respectively. A statistical relationship between ultrasonic and histology measurements was only found, however, for assessment of wall thickness (r = 0.71).The identification of small ablation effects by ICUS was possible with great accuracy and ELCA could be performed without penetration of the adventitial layers. However, exact quantification of the crater dimensions was not possible due to limitations of the axial and lateral resolution. Thus, for the guidance of ELCA by ICUS a further improvement in the resolution capabilities of ICUS devices is mandatory.

OBJECTIVE:To evaluate the effect of drug on chemical degradation of lipopolysaccharide (LPS) from oral anaerobes.METHODS:LPSs from porphyromonas gingivalis (Pg),bacteroides fragilis (Bf) and fusobacteria nucleatum (Fn) were extracted by the hot phenol-water method and purified by the phenol-chloroform-petroleum ether procedure.1.0 ml (200microg) various LPSs were incubated with 2.0 ml various drugs at 37degrees centigrade for 15 or 30 minutes in vitro,respectively.The chemical degradation of LPS was quantitated by limulus synthetic chromogenic substrated method after dialysis.RESULTS:The order of degradation was 30% hydrogen peroxide (H),50% citric acid (C),garlic guice (G),1:1 diluted G,25% C and 3% H,and their efffcts were dose dependent and were time dependent except H but the effect of lysozyme was minimal.CONCLUSION:The study may imply that the dose and the mechanism of various drugs on LPS degradation are different and remains to be elucidated.

The induced mutation frequency by alkylating mutagen glycidyl methacrylate (GMA) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated with or without perturbation of deoxyribonucleoside triphosphate (dNTP) pools; the influence of short treatment at different concentrations of GMA or MNNG on dNTP pools was also explored. The results indicated that the induced mutation frequency increased greatly at high dosages of mutagen (GMA approximately 64 micrograms/ml, MNNG approximately 8 micrograms/ml) and the perturbation on dNTP pools was carried out before the treatment of mutagen; the short treatment with mutagen could induce distinct fluctuations of dNTP pools, but different mutagen might have different effects on dNTP pools. According to the results of the present study and other reports in literature, we conclude that dNTP pools may be the targets of alkylating mutagens and the fluctuations of dNTP pools are closely associated with mutagenesis.

Deoxyribonucleoside triphosphate (dNTP) pools were measured in normal BALB/c3T3 cells, transformation-treated cells and transformed cells with reverse-phase HPLC. The fluctuation of dNTP pools was similar after transformation treatment with alkylating mutagen glycidyl methacrylate (GMA) or Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). However, the gap between deoxyguanosine triphosphate + deoxyadenosine triphosphate (dGTP + dATP) pools and deoxythymidine triphosphate + deoxycytidine triphosphate (dTTP + dCTP) pools was greatly intensified. The measurements also indicated that the dNTP pools in transformed cells were quite different from those in normal cells. The results suggested that dNTP pools may play an important role in cell transformation.

Bereits 1911 wurde unter Claudicatio intermittens-Patienten eine drei- bis funffache Haufung von Rauchern beobachtet. In der Zwischenzeit gibt es keinen Zweifel mehr daran, das Rauchen einer der Risikofaktoren der Arteriosklerose ist [6, 7, 10]. Ein wichtiger Bestandteil des Zigarettenrauches ist das Nikotin. Seine potentiell schadigende Wirkung auf Endothel- und glatte Muskelzellen wurde nachgewiesen [3, 7, 10]. In dieser Studie wurde untersucht, ob eine direkte Wirkung von Nikotin auf das Proliferationsverhalten glatter Muskelzellen und Endothelzellen in vivo nachzuweisen ist und ob praformierte Gefaswandplaques durch Nikotineinwirkung in ihrem weiteren Wachstum stimulierbar sind.

Ziel der Untersuchung war die Bestimmung der proliferativen Reaktion glatter Muskelzellen in der Intima sowie der Haufigkeit thrombotischer Verschlusse nach Stentimplantation im Vergleich zur konventionellen Ballondilatation. Hierzu wurden an der Arteria carotis von 27 Neuseeland-Kaninchen ballonexpandierbare Strecker-Stents implantiert beziehungsweise bei 29 Tieren eine Ballonangioplastie durchgefuhrt. Zehn Tiere dienten als Kontrollgruppe ohne Intervention. Die Tiere erhielten unmittelbar praoperativ sowie postoperativ fur insgesamt drei Tage unfraktioniertes Heparin. Die Gefase wurden 7, 14, 28 und 42 Tage nach Intervention entnommen und histologisch aufgearbeitet. Die Gabe von Bromdesoxyuridin ermoglichte die immunhistologische Bestimmung der neointimalen Proliferationsrate, wobei die glatten Muskelzellen mit einem Antikorper gegen a-Aktin identifiziert wurden. Am 7. Tag nach Intervention zeigte sich eine stark gesteigerte Proliferation glatter Muskelzellen sowohl nach Stentimplantation (16,2 ± 3,7%) als auch nach konventioneller Ballon-angioplastie (12,5 ± 4,8%). Wahrend die Proliferationsrate nach Ballon-angioplastie am 42. Tag jedoch auf den Wert der Kontrollgruppe (0,3 ± 0,4%) zuruckgekehrt war, fand sich nach Stentimplantation eine immer noch signifikante Erhohung der Proliferation (2,7 ± 0,3%; p < 0,0001). Auserdem war die Inzidenz thrombotischer Komplikationen nach Stentimplantation deutlich hoher (25,9% vs. 6,8%). Zusammenfassend weisen unsere Daten auf eine gesteigerte und prolongierte proliferative Reaktion glatter Muskelzellen nach Stentimplantation im Vergleich zur Ballondilatation hin.

The following experiments were conducted to evaluate the genotoxic effects of GMA (glycidyl methacrylate) on mammalian and human cells. (1) Using the absorption spectrum shift method in vitro, we observed that the maximums of calf thymus DNA and GMA were shifted toward longer wavelengths (a change of more than 15 nm) and the absorbance decreased after incubation at room temperature for 15 min or more. The result indicates that binding of DNA and GMA had occurred. The binding force is strong, not affected by the addition of concentrated sodium chloride solution, and only slightly decreased by the addition of 8 M urea solution. Therefore the bond between DNA and GMA might be covalent. (2) In cell cultures, unscheduled DNA synthesis (UDS) in human and/or rat lymphocyte was induced and DNA semiconservative replication was inhibited by GMA at concentrations of less than 5.2 mM. (3) Sperm abnormality tests and assays of UDS in germ cells of male mice were conducted to study the in vivo genotoxicity of GMA. The results revealed that GMA could damage DNA, increase sperm abnormality frequency, and reduce the number of sperm cells.

Glycidyl methacrylate (GMA) is a recently recognized chemical mutagen. In order to explore the mutagenicity and mutagenic process of GMA, plasmid pBR322 was used for in vitro binding, mutant screening, and restriction enzyme mapping. The binding between GMA and DNA in vitro has been verified by means of a spectrophotometric method. When pBR322 and GMA-bound pBR322 were used to transform Escherichia coli HB101, the following results were obtained: (1) The transformation efficiency of GMA-bound pBR322 was much lower than that of pBR322 alone. (2) GMA-bound pBR322 induced phenotype changes in competent cells (i.e., tetracycline-resistance inactivation or ampicillin-resistance inactivation). There were two mutants of pBR322, ApRTCS and ApSTcR, in the transformants and a deductive mutant ApsTcs in the nontransformants. (3) All of the selected mutants were stable and heritable. (4) When restriction enzyme maps were used to analyze the mutant ApRTcS, four of seven maps were changed, some sites were shifted to other resistant gene regions, for example, sites of Bg/I, EcoRI, HindIII, HincII, etc., and there was a new recognition site for HincII (252). We did not observe any DNA fragment insertion or deletion on any maps. Our results suggest that when GMA is covalently linked to the plasmid DNA, it gives rise to a premutagenic lesion of DNA that is converted in vivo into a point mutation.

Laser irradiation offers the potential of removing atherosclerotic plaques from blood vessels. We used the Nd:YAG laser to treat coronary atherosclerotic obstruction in patients undergoing coronary bypass. Of the 7 patients treated, all were successfully recanalized without damage to the artery wall (a mild hematoma developed in 1 case), and follow-up examination showed patency 4 months after operation. We conclude that Nd:YAG laser shows promise for the treatment of atherosclerotic obstructions, but more study is needed before wide clinical application is justified.

This study was to assess the potential application of excimer lasers in the ablation of myocardium in vitro for the treatment of constant ventricular tachycardia or hypertrophic cardiomyopathy. A fresh human heart and EMG model 103 XeCl pulse excimer laser machine were used. The pulse repetition rate varied from 1 to 7 Hz. Irradiation directly on the left endocardial and epicardial walls lasted for 10 seconds and was repeated 3 times, creating 3 craters. The histological changes were examined by light microscope. Results showed very close relations between the depth or volume of vaporized craters and the pulse repetition rate on the endocardial (r = 0.9674, P less than 0.001 and r = 0.8962, P less than 0.01, respectively) and epicardial walls (r = 0.9602, P less than 0.001 and r = 0.9612, P less than 0.001, respectively). A sharp, clear border without debris or coagulating necrosis was seen under the microscope. We concluded that the pulse excimer laser, differing from Ar+ or Nd:YAG lasers, might be a powerful tool for manipulating the human ventricular wall, but more work needs to be done before it can be widely applied in the treatment of cardiovascular disease.