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Background and Aim: Intestinal ischemia/reperfusion (II/R) can cause injury of remote organs, including acute renal injury. All of these, in turn, increase the rate of disability and mortality. Anwulignan (Anwu) is an active monomer from Schisandra sphenanthera, which has been used for thousands of years in China as a medical herb. In our previous study, we found that Anwu can improve the intestinal function after ischemia/reperfusion. Therefore, we were curious to know if Anwu can have a protective effect on remote organ injury after II/R. The purpose of the present study was to examine the effect of Anwu on the remote renal injury induced by II/R in rats and investigate its mechanism. Materials and Methods: Forty Sprague Dawley (SD) rats were divided into four groups, and they were sham operation (Sham), sham + Anwu, II/R, and II/R + Anwu groups. After reperfusion or sham operation, blood and kidneys were collected from the rats for the detection of relative biochemical parameters. Results: Renal indexes were not significantly different among all groups. In the II/R group the following were the findings: blood urea nitrogen and creatinine levels were increased, kidney injury score was increased, renal superoxide dismutase was reduced, the activities of reduced glutathione and catalase were decreased, the renal malondialdehyde content was increased, there was an improvement in the levels of renal proinflammatory cytokines, interleukin-6, tumor necrosis factor-α, and interleukin-1β, the expressions of renal oxidative stress-related p-Nrf2 and heme oxygenase (decycling) 1 (HO-1) were decreased, and the Kelch-like ECH-associated protein 1 (Keap1) expression was increased. The expression levels of the apoptotic protein, cleaved caspase-3, were raised, while the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated x protein (Bax) ratio was reduced. However, the administration of Anwu before the surgery significantly reversed the above changes. Conclusion: Anwu has a protective effect against the II/R-induced remote renal injury in rats, which may be related to its regulation of antioxidant, anti-inflammatory, and antiapoptotic pathways. [ABSTRACT FROM AUTHOR]

• A 3D-OHP with ammonia and liquid metal was first developed for high-power and high-heat-flux dissipation. • Liquid metal can promote the unidirectional flow in the OHP. • Liquid metal improves the heat absorption and release rate of the working fluid. • The 3D-OHP can effectively handle heat dissipation of 1000 W with local heat flux of 111 W/cm2. With the rapid development of microelectronics technology, the power of some advanced electronic devices has reached 1000 W with heat flux of 100 W/cm2. The problem of high-power and high-heat-flux thermal management has become the bottleneck of the development of advanced electronic devices. In this paper, a three-dimensional oscillating heat pipe (3D-OHP) with 18 channels was developed for this problem. A new hybrid fluid of ammonia and liquid metal was used as a working fluid. The wall temperature and heat transfer performance of the 3D-OHP charged with the hybrid fluid were investigated experimentally. The results indicate that the 3D-OHP can effectively solve the problem of heat dissipation with the heating power of 1000 W and the heat flux of 111.1 W/cm2. Liquid metal can ensure the efficient operation of ammonia OHP under supercritical pipe diameter, and promote the working fluid to form a unidirectional flow. Liquid metal has a great ability to absorb and release heat which significantly enhances the heat transfer performance of the 3D-OHP. When the heat flux reached 111 W/cm2, the 3D-OHP with 2.11% liquid metal had the best heat transfer performance, and the thermal resistance was 0.0351 °C/W. Compared with pure ammonia 3D-OHP, it could reduce the temperature difference of the 3D-OHP by 9.1 °C and enhance the heat transfer performance by 20.57%. The capacity of the ammonia-liquid metal 3D-OHP to deal with high-power and high-heat-flux is higher than the existing studies. [ABSTRACT FROM AUTHOR]

The hierarchy of events accompanying induction of apoptosis by the proteasome inhibitor Bortezomib was investigated in Jurkat lymphoblastic and U937 myelomonocytic leukemia cells. Treatment of Jurkat or U937 cells with Bortezomib resulted in activation of c-Jun-N-terminal kinase (JNK) and p38 MAPK (mitogen-activated protein kinase), inactivation of extracellular signal-regulating kinase 1/2 (ERK1/2), cytochrome c release, caspase-9, -3, and -8 activation, and apoptosis. Bortezomib-mediated cytochrome c release and caspase activation were blocked by the pharmacologic JNK inhibitor SP600125, but lethality was not diminished by the p38 MAPK inhibitor SB203580. Inducible expression of a constitutively active MEK1 construct blocked Bortezomib-mediated ERK1/2 inactivation, significantly attenuated Bortezomib lethality, and unexpectedly prevented JNK activation. Conversely, pharmacologic MEK/ERK1/2 inhibition promoted Bortezomib-mediated JNK activation and apoptosis. Lastly, the antioxidant N-acetyl-l-cysteine (LNAC) attenuated Bortezomib-mediated reactive oxygen species (ROS) generation, ERK inactivation, JNK activation, mitochondrial dysfunction, and apoptosis. In contrast, enforced MEK1 and ERK1/2 activation or JNK inhibition did not modify Bortezomib-induced ROS production. Together, these findings suggest that in human leukemia cells, Bortezomib-induced oxidative injury operates at a proximal point in the cell death cascade to antagonize cytoprotective ERK1/2 signaling, promote activation of the stress-related JNK pathway, and to trigger mitochondrial dysfunction, caspase activation, and apoptosis. They also suggest the presence of a feedback loop wherein Bortezomib-mediated ERK1/2 inactivation contributes to JNK activation, thereby amplifying the cell death process. [Copyright &y& Elsevier]

With the highly integrated development of electronic components, higher requirements are put forward for heat transfer components, there is an urgent need for high-performance heat transfer components. Oscillating heat pipe (OHP) is novel types of heat pipe with excellent heat transfer capability. However, the heat transfer limit hinders their operation and application. This paper proposes an OHP under trans-critical conditions with the working fluid of R218 and explores its operating characteristics and heat transfer capability. Visualization experiments and pressure monitoring were conducted to analyze the state changes within the OHP under trans-critical conditions. After evaporation section temperature surpassing the critical temperature of R218, the pressure increases with the temperature, once the pressure reached near the critical pressure, OHP can transcend the limitation of the critical temperature and realize efficient oscillating operation under trans-critical conditions. With stable operation, the working fluid velocity can reach up to 1.49 m/s, and the OHP under trans-critical conditions presented excellent heat transfer performance with the thermal resistance of 0.22 °C/W. This paper proves the feasibility of the OHP under trans-critical conditions and provides a basis for further research. [ABSTRACT FROM AUTHOR]

Ammonium paratungstate (APT) is an important intermediate for the production of tungsten-containing products. However, its morphology problems caused by crystal agglomeration affect its properties. In this paper, the mechanism of agglomeration during the evaporative crystallization of APT was studied. The experimental result reveals that the temperature, as a critical parameter, significantly affects hydrates purification of crystallization. Combined with on-line and off-line analysis, it is proposed that the crystal agglomeration mainly results from hydrate transformation from heptahydrate to pentahydrate. Furthermore, based on this agglomeration mechanism, the strategy of adding seeds was applied to control the supersaturation within the metastable region and to avoid the nucleation of heptahydrates. The effect of seeds properties, such as the effect of its mass and size on the particle size distribution and agglomeration degree of the products, were investigated in batch crystallization. Finally, we obtained monodisperse crystals of pure APT·5H 2 O with better performance. [Display omitted] • Controllable preparation of pure monodisperse APT·5H 2 O crystals. • Investigate the mechanism of agglomeration and transcrystallization of APT. • The bulk density increased from 1.9 g/cm3 to 2.3 g/cm3 and the angle of repose decreased from 45° to 34°. [ABSTRACT FROM AUTHOR]

Abstract: YM155, a small-molecule survivin suppressant, exhibits anti-tumor activities in vitro, in vivo and in clinical trials. However, the mechanism of YM155 action remains unclear. In this study, YM155 was administered to a panel of cell lines and the effects of YM155 on Bcl-2 family members were analyzed. Our results show that YM155 strikingly downregulates Mcl-1 in a broad spectrum of cancer cell lines and that the Mcl-1 modulation occurs at the transcriptional level, independently of survivin modulation or caspase activity. Furthermore, analysis of the contribution of Mcl-1 or survivin downregulation to YM155-induced cell death in vitro showed that knockdown of Mcl-1 sensitizes cells to YM155-induced cytotoxicity. Finally, our data demonstrate that downregulation of Mcl-1 by YM155 synergistically lowers the threshold of Bcl-2 family member inhibitor ABT-263-induced cell death. Our findings reveal a novel mechanism by which survivin-independent Mcl-1 suppression plays a critical role in YM155-mediated anti-tumor activities. YM155 treatment in combination with ABT-263 thus affords a new strategy for cancer treatment. [Copyright &y& Elsevier]

Generally, the oscillating heat pipe (OHP) diameter should be kept below a specific critical size. As a result, the working fluid forms a vapor-liquid slug train under the capillary action, producing a gas-spring-mass mechanical vibration system. Determining the critical diameter is essential for the OHP to form this slug train. A conventional critical diameter model only considers the surface tension and gravity. However, the vapor bubble flow in the liquid slug plays a key role in forming this essential slug train. Even if the hydraulic diameter of an OHP is much larger than the conventional critical diameter, the OHP can still function. The dynamic flow significantly affects the formation of the vapor-liquid slug-train. Therefore, a semi-empirical model was developed considering the effects of the dynamic flow and the heat input, filling ratio, and working fluid. The concept of dynamic critical diameter (DCD) was proposed. The model shows that the OHP DCD increases when the heat input increases for a given evaporator temperature. In addition, the model can predict that the OHP DCD decreases when the evaporator temperature increases. • The concept of dynamic critical diameter (DCD) was proposed. • The mechanism of vapor-liquid plugs formation in OHP with pipe diameters exceeding conventional MCD is revealed. • A semi-empirical DCD model was developed. • The filling ratio should be between the values of 0.24 and 0.75 when the diameter exceeds MCD. [ABSTRACT FROM AUTHOR]

• Gallium-based liquid metal-copper foam TIM is prepared by galvanic corrosion. • The thermal conductivity of the TIM is 51.58±0.01 W/(m·K). • Under the pressure of 0.35 MPa, the TIM does not overflow. • With the increase in wettability, the thermal contact resistance decreased by 58.28%. As a promising thermal interface material (TIM), gallium-based liquid metal (GBLM) could significantly reduce the thermal contact resistance (TCR) at the solid-solid interfaces, while the leakage of GBLM and the wettability between liquid metal and solid surface restrict further application. In this study, the GBLM was wrapped with a copper foam (CF) skeleton, which prevents leakage and improves the thermal conductivity of the GBLM. Gallium-based liquid metal-copper foam (GBLM-CF) TIM was prepared by the self-wetting of the CF surface through the galvanic corrosion of GBLM. As the concentration of HCl increases from 0 to 5 M, the interfacial tension (IFT) in the HCl solution decreases from 536.80±1.00 mN/m to 481.52±0.49 mN/m, demonstrating that the IFT of the GBLM is inversely proportional to the concentration of HCl. Meanwhile, the decrease of contact angle (CA) by 8° indicates that the presence of CuGa 2 on the surface promotes the wettability of GBLM. With the increase of external pressure and the improvement of wettability, the TCR between the GBLM and the copper sheet decreased by 58.28%. The TCR of the sample using GBLM-CF as TIM is 83% lower than that of thermal grease. Moreover, the thermal conductivity of GBLM-CF TIM (51.58±0.01 W/(m·K)) is 212.6% higher than that of GBLM (16.50±0.02 W/(mK)). The GBLM-CF TIM presented in this study can be used for the efficient thermal management of electronic equipment. [ABSTRACT FROM AUTHOR]

Background and Purpose Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb S tephaniae tetrandrae, has a long history in Chinese clinical applications to treat diverse diseases. Tetrandrine induced apoptosis or, at low concentrations, autophagy of human hepatocellular carcinoma cells. Here we have tested the effects of inhibitors of autophagy such as chloroquine, on the response to low concentrations of tetrandrine in cancer cells. Experimental Approach Cultures of several cancer cell lines, including Huh7, U251, HCT116 and A549 cells, were exposed to tetrandrine, chloroquine or a combination of these compounds. Cell viability and content of reactive oxygen species (ROS) were measured and synergy assessed by calculation of the combination index. Western blot and RT-PCR assays were also used along with fluorescence microscopy and histochemical techniques. Key Results Combinations of tetrandrine and chloroquine were more cytotoxic than the same concentrations used separately and these effects showed synergy. Such effects involved increased ROS generation and were dependent on caspase-3 but independent of Akt activity. Blockade of tetrandrine-induced autophagy with 3-methyladenine or bafilomycin-A1 induced apoptosis in cancer cells. Lack of p21 protein (p21−/− HCT116 cells) increased sensitivity to the apoptotic effects of the combination of tetrandrine and chloroquine. In a tumour xenograft model in mice, combined treatment with tetrandrine and chloroquine induced ROS accumulation and cell apoptosis, and decreased tumour growth. Conclusions and Implications The combinations of tetrandrine and chloroquine exhibited synergistic anti-tumour activity, in vitro and in vivo. Our results suggest a novel therapeutic strategy for tumour treatment. [ABSTRACT FROM AUTHOR]

• A guideline to optimize the structure of 3DCOHP was proposed, which can enhance the heat transfer performance significantly. • Reducing the top bend curvature radius of 3DCOHP with asymmetric heating mode can promote the formation of unidirectional flow without check valve. • The existence of unequal flow pressure drop between the push-up and push-down causes the formation of unidirectional flow in 3DCOHP. The effects of the bend curvature radius and tube diameter on the heat transfer performance of the three-dimensional coil oscillating heat pipe (3DCOHP) were experimentally studied in asymmetric heating mode. Three types of copper 3DCOHPs using water as the working fluid were studied in vertical orientation. And the filling ratio of each 3DCOHP was set to 50%. It was found that reducing the top bend curvature radius and increasing the tube diameter can both strengthen the formation of unidirectional flow and significantly improve the heat transfer performance of the 3DCOHP. The heat transfer performance of the OHP with a tube diameter of 1.90 mm increased by up to 34.6% when the heating power was set to 40 W. At the same time, the reason of the unidirectional flow in asymmetric heating mode was theoretically analyzed. It was shown that the calculated pressure drops in liquid slug flowing from the evaporation section to both sides powered by vapor expansion are different, which develops the unidirectional flow. These findings provide a guideline to optimize the structure of OHP to enhance its heat transfer capacity. [ABSTRACT FROM AUTHOR]

Background and Purpose: Sorafenib, a potent inhibitor that targets several kinases associated with tumourigenesis and cell survival, has been approved for clinical treatment as a single agent. However, combining sorafenib with other agents improves its anti-tumour efficacy in various preclinical tumour models. ABT-263, a second-generation BH3 mimic, binds to the anti-apoptotic family members Bcl-2, Bcl-xL and Bcl-w, and has been demonstrated to enhance TNFSF10 (TRAIL)-induced apoptosis in human hepatocarcinoma cells. Hence, we investigated the effects of ABT-263 treatment combined with sorafenib.Experimental Approach: The effects of ABT-263 combined with sorafenib were investigated in vitro, on cell viability, clone formation and apoptosis, and the mechanism examined using western blot and flow cytometry. This combination was also evaluated in vivo, in a mouse xenograft model; tumour growth, volume and weights were measured and a TUNEL assay performed.Key Results: ABT-263 enhanced sorafenib-induced apoptosis while sparing non-tumourigenic cells. Although ABT-263 plus sorafenib significantly stimulated intracellular reactive oxygen species production and subsequent mitochondrial depolarization, this was not sufficient to trigger cell apoptosis. ABT-263 plus sorafenib significantly decreased Akt activity, which was, at least partly, involved in its effect on apoptosis. Bax and p21 (CIP1/WAF1) were shown to play a critical role in ABT-263 plus sorafenib-induced apoptosis. Combining sorafenib with ABT-263 dramatically increased its efficacy in vivo.Conclusion and Implications: The anti-tumour activity of ABT-263 plus sorafenib may involve the induction of intrinsic cell apoptosis via inhibition of Akt, and reduced Bax and p21 expression. Our findings offer a novel effective therapeutic strategy for tumour treatment. [ABSTRACT FROM AUTHOR]

Background and purpose Sorafenib, a potent inhibitor that targets several kinases associated with tumourigenesis and cell survival, has been approved for clinical treatment as a single agent. However, combining sorafenib with other agents improves its anti-tumour efficacy in various preclinical tumour models. ABT-263, a second-generation BH3 mimic, binds to the anti-apoptotic family members Bcl-2, Bcl-xL and Bcl-w, and has been demonstrated to enhance TNFSF10 (TRAIL)-induced apoptosis in human hepatocarcinoma cells. Hence, we investigated the effects of ABT-263 treatment combined with sorafenib. Experimental Approach The effects of ABT-263 combined with sorafenib were investigated in vitro, on cell viability, clone formation and apoptosis, and the mechanism examined using western blot and flow cytometry. This combination was also evaluated in vivo, in a mouse xenograft model; tumour growth, volume and weights were measured and a TUNEL assay performed. Key Results ABT-263 enhanced sorafenib-induced apoptosis while sparing non-tumourigenic cells. Although ABT-263 plus sorafenib significantly stimulated intracellular reactive oxygen species production and subsequent mitochondrial depolarization, this was not sufficient to trigger cell apoptosis. ABT-263 plus sorafenib significantly decreased Akt activity, which was, at least partly, involved in its effect on apoptosis. Bax and p21 ( CIP1/WAF1) were shown to play a critical role in ABT-263 plus sorafenib-induced apoptosis. Combining sorafenib with ABT-263 dramatically increased its efficacy in vivo. Conclusion and Implications The anti-tumour activity of ABT-263 plus sorafenib may involve the induction of intrinsic cell apoptosis via inhibition of Akt, and reduced Bax and p21 expression. Our findings offer a novel effective therapeutic strategy for tumour treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: The mammalian target of rapamycin (mTOR) plays a pivotal role in hepatocellular carcinoma (HCC). Previous studies indicated that inhibition of mTORC1 enhanced histone deacetylase inhibitors (HDACis)-mediated anti-tumor activity, accompanied with feedback activation of AKT. Therefore, dual targeting of mTORC1/C2 should be more efficient in suppressing AKT activity and in enhancing the anti-tumor activity of HDACi in HCC. Methods: The interactions between mTOR kinase inhibitors (mTORKis) (i.e., Pp242, AZD8055, OSI027) and HDACis (i.e., SAHA, LBH589) were examined in vitro using HCC cell lines and in vivo using patient-derived primary HCC xenografts on SCID mice. Results: mTORKis significantly enhanced HDACi-induced apoptosis in HCC cells. The inhibition of both mTORC1/2 not only efficiently blocked mTORC1 signaling, but also abrogated AKT-feedback activation caused by selective mTORC1 inhibition. The co-treatment of mTORKi and HDACi further inhibited AKT signaling and upregulated Bim. Dysfunction of mTORC2 by shRNA significantly lowered the threshold of HDACi-induced cytotoxicity by abrogating AKT activation. Knockdown of AKT1 sensitized Pp242/HDACi-induced apoptosis and ectopic expression of constitutively active AKT1 abrogated the combination-induced cytotoxicity, indicating AKT plays a vital role in the combination-induced effects. Knockdown of Bim prevented Pp242/HDACis-induced cytotoxicity in HCC. Lastly, in vivo studies indicated that the combination of AZD8055 and SAHA almost completely inhibited tumor-growth, without obvious adverse effects, by abrogating AKT and upregulating Bim; while either agent alone shows only 30% inhibition in primary HCC xenografts. Conclusions: Our findings suggest that a combining-regimen of mTORKi and HDACi may be an effective therapeutic strategy for HCC. [ABSTRACT FROM AUTHOR]

Abstract: An acoustic-optic Q-switched YAG laser is newly developed for truing and dressing of bronze-bonded diamond grinding wheels through ablation in the radial direction. The laser ablation merges truing and dressing as a single process and can be easily controlled through an online closed-loop control system. The laser truing and dressing characteristics are investigated by wheel surface topography and a high-speed grinding test. A two-dimensional mathematical model is developed to simulate laser truing and dressing of bronze-bonded diamond grinding wheel. Based on the model, the ablation depth produced on bond and diamond abrasives by a pulsed laser under different parameters as well as the temperature field on grinding wheel surface produced in the laser ablation process are numerically simulated. Both the experimental results and the theoretical analysis indicate that the truing and dressing processes can be simultaneously realized with the laser ablation. [Copyright &y& Elsevier]

• A liquid metal high temperature OHP (LMHOHP) was first developed. • The LMHOHP that can function at a temperature of over 500 °C. • The LMHOHP can transport heat of 3169 W and achieve a thermal resistance of 0.08 °C/W. This paper introduces the development of a liquid metal high-temperature oscillating heat pipe (LMHOHP) that can function under high-temperature conditions (over 500 °C). The LMHOHP has six turns with a total height of 310 mm. The sodium-potassium alloy (potassium 78%) was used as the working fluid, and the 310S stainless steel tube with an inner diameter of 6 mm as the shell tube. The LMHOHP heat transfer performance was investigated experimentally with a filling ratio of 45% at different input powers. Experimental results show that the LMHOHP can effectively generate steady-state oscillating motions at a working temperature of over 500 °C. When the steady-state oscillating motions exist, the temperature difference and thermal resistance between the evaporator and condenser were reduced significantly. At a heat input of 3169 W, the LMHOHP presents a minimum thermal resistance of 0.08 °C/W. This LMHOHP provides a new approach to next-generation high-temperature cooling devices. [ABSTRACT FROM AUTHOR]