Microwave ablation on ex vivo porcine pancreas: The influence of ablation parameters on ablation results and fat liquefaction.

The pancreas is adjacent to critical organs; excessive microwave ablation (MWA) can result in serious complications. The purpose of this paper is to provide the reference data of pancreas MWA for clinicians, analyze the ablation outcomes under different ablation parameters, and determine the critical temperature of pancreatic surface fat liquefaction outflow. Combinations of two power levels (30 W and 55 W), three antenna diameters (1.3 mm, 1.6 mm, and 1.9 mm), and three ablation times (1 min, 1.5 min, and 2 min) were applied to an ex vivo pig pancreas. Temperature measurements were taken at four thermocouple points. The center point is located 5 mm horizontally from the antenna slot, with a temperature measurement point located 5 mm above, below, and to the right of the center point. Main effect analysis and variance analysis were used to quantify the influences of each factor on the ablation outcomes. At 30 W, the antenna diameter contributing the most at 48.5%. At 30 W-1.3 mm-1 min, the spherical index (1.41) is closest to 1. At 55 W, the coagulation zone size was almost only affected by the ablation time, with a contribution rate of 28.7%, the temperature at point C exceeds point B. On the surface of the ex vivo porcine pancreas, the fat outflow temperature was 54ã. Ablation combinations with low power, short duration, and small antenna diameter results in a more nearly spherical coagulation zone. When performing MWA on the pancreas, it is advisable to avoid areas with higher fat content, while keeping the pancreatic surface temperature below 54°C.

Recent research advances on simulation modeling of temperature distribution in microwave ablation of lung tumors.

Lung tumor is the first malignant tumor with the highest mortality, but only no more than one-third of patients can be treated by surgical resection. Microwave ablation (MWA) has become a new adjuvant therapeutic mean for lung tumors because of its low trauma, short treatment time, large ablation volume and wide application range. However, the treatment parameters of MWA, such as input power and ablation time, still depend on the doctors' experience, which leads to the ineffectiveness of MWA. Therefore, the accurate modeling of temperature distribution of lung tumor MWA has become a significant technical problem to be solved. Recent research was devoted to personalized characterization of lung tumor parameters, finite element analysis of temperature distribution in MWA and accurate ablation effect evaluation. In this paper, a review of the recently obtained results and data will be presented and discussed.

miR-3133 is an unfavorable prognosis factor and tumor suppressor in colon cancer.

Dysregulated miRNAs have been demonstrated to be associated with the progression of colon cancer. The dysregulation of miR-3133 was observed in colon cancer, but its specific function was unclear. The functional role of miR-3133 in colon cancer was investigated in this study. A total of 113 colon cancer patients were included. miR-3133 expression was evaluated by PCR. The biological effects of miR-3133 in colon cancer cells were assessed with the help of the transwell and CCK8 assay. The prognostic value of miR-3133 was estimated by a series of statistical analyses. In mechanism, the interaction between miR-3133 and RUFY3 was evaluated by luciferase reporter. The significant downregulation of miR-3133 was observed in colon cancer, which showed a significant association with the advanced TNM stage and bad survival of patients. miR-3133 and TNM stage were identified as independent prognostic indicators of colon cancer. In vitro, the overexpression of miR-3133 exerted a dramatically inhibitory effect on cellular processes of colon cancer, which were enhanced by miR-3133 knockdown. Additionally, miR-3133 could negatively regulate the luciferase activity and expression of RUFY3, which was speculated as the underlying mechanism mediating the regulatory effect of miR-3133. miR-3133 functioned as a prognostic biomarker indicating the progression and prognosis of colon cancer, and it also served as a tumor suppressor via negatively regulating RUFY3, which provides a potential therapeutic target for colon cancer.

The Efficacy and Safety of Zhengqing Fengtongning for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Zhengqing Fengtongning release tablet (ZQFTN) is a proprietary Chinese medicine preparation of sinomenine, the main active component of the traditional Chinese medicine (TCM) Sinomenium acutum. It is used in China as a complementary and alternative medicine (CAM) for knee osteoarthritis (KOA). The objective of this study was to evaluate the clinical efficacy and safety of ZQFTN in KOA treatment. METHOD: Randomized controlled trials of ZQFTN in KOA treatment were searched in PubMed, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang database. Two reviewers independently conducted the screening, extracted the data, and assessed the methodological quality. Statistical analysis was performed using RevMan 5.3 software. RESULTS: Eighteen studies were assessed that included 1512 participants (757 in the treatment group and 755 in the control group). The results showed that compared with the control group, the Visual Analogue Scale (standardized mean difference (SMD) = -0.87, 95% confidence interval (CI): [-1.08, -0.66], P < 0.001), Western Ontario and Mc Master University (WOMAC) Osteoarthritis Index pain score (SMD = -0.67, 95% CI: [-0.88, -0.46], P < 0.001), WOMAC stiffness score (SMD = -0.53, 95% CI: [-0.86, -0.20], P=0.001), WOMAC function score (SMD = -0.76, 95% CI: [-0.97, -0.55], P < 0.001), serum interleukin-1ß level (SMD = -4.36, 95% CI: [-6.41, -2.31], P < 0.001), and serum tumor necrosis factor-α level (SMD = -8.45, 95% CI: [-11.20, -5.69], P < 0.001) of the ZQFTN treatment group were lower, and the total effective rate was higher relative risk (RR = 1.15, 95% CI [1.07, 1.23], P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups (RR = 0.96, 95% CI: [0.69, 1.35], P=0.82). CONCLUSION: ZQFTN can effectively relieve knee pain, morning stiffness, and daily activity function disorders, reduce the expression of inflammatory factors in serum, and improve the total clinical response rate without increasing the incidence of adverse reactions. Therefore, ZQFTN has considerable potential as a CAM for KOA. However, due to the limitation of the quality of the included studies, the strength of this conclusion is affected. In the next step, multicenter, large sample, high-quality randomized controlled studies are needed to further confirm the present conclusion.

Mesenchymal Stem Cell-Derived Exosomes Attenuate Epithelial-Mesenchymal Transition of HK-2 Cells.

Renal fibrosis (RF) predisposes patients to an increased risk of progressive chronic kidney disease, and effective treatments remain elusive. Mesenchymal stem cell (MSC)-derived exosomes are considered a new treatment for tissue damage. Our study aimed to investigate the in vitro effects of bone marrow MSC-derived exosomes (BM-MSC-Exs) on transforming growth factor-ß1 (TGF-ß1)-induced fibrosis in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. Herein, we found BM-MSC-Exs could inhibit TGF-ß1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells, and may involve autophagy activation of BM-MSC-Exs. Moreover, we first reported that after ceria nanoparticles (CeNPs) treatment, the improvements induced by BM-MSC-Ex on EMT were significantly enhanced by upregulating the expression of Nedd4Lof MSCs and promoting the secretion of exosomes, which contained Nedd4L. In addition, Nedd4L could activate autophagy in HK-2 cells. In conclusion, BM-MSC-Ex prevents the TGF-ß1-induced EMT of renal tubular epithelial cells by transporting Nedd4L, which activates autophagy. The results of this in vitro experiment may extend to RF, whereby BM-MSC-Ex may also be used as a novel treatment for improving RF. Impact statement Renal fibrosis (RF) is an important pathological change in chronic kidney disease that ultimately leads to end-stage renal failure, and effective treatments remain elusive. In this study, there are two contributions. First, our results suggest that bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exs) can prevent transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells through Nedd4L trafficking, which activates autophagy. Second, the improvement effects of BM-MSC-Ex on TGF-ß1-induced HK-2 EMT can be enhanced by ceria nanoparticles (CeNPs). The findings in this study may be extended to RF: BM-MSC-Exs may be used as a novel treatment to improve RF.

Comparison of the Rheological Properties and Structure of Fat Derivatives Generated via Different Mechanical Processing Techniques: Coleman Fat, Nanofat, and Stromal Vascular Fraction-Gel.

Importance: Coleman fat, nanofat, and stromal vascular fraction-gel (SVF-gel) are three widely used fat derivatives. However, their rheological properties and structure remain unknown. Objectives: To disclose the rheological properties and structure of three different fat derivatives. Design, Settings, and Participants: Fat tissues obtained from eight different donors were processed into three separate groups: Coleman fat, nanofat, and SVF-gel (n = 8); their viscoelastic properties and structure were determined. Intervention: Oscillation measurements were performed in the context of serrated 25-mm parallel-plate geometry with a 1.2-mm gap at 25°C. In addition, fat samples were fixed using a patented protocol and observed under scanning electron microscopy. Main Outcomes and Measures: Comparison of the viscoelastic properties, microstructure, and particle size. Results: At 0.77 Hz, the elastic modulus of SVF-gel, Coleman fat, and nanofat was 201.6 ± 0.74, 69.94 ± 15.61, and 34.89 ± 3.484 Pa, respectively; their viscosity was 44.06 ± 3.038, 15.37 ± 2.0380, and 7.516 ± 0.7250 mPa, respectively. The particle size of SVF-gel, Coleman fat, and nanofat was 106.0 ± 4.796, 86.93 ± 3.597, and 12.61 ± 7.603 µm, respectively. Conclusion and Relevance: Mechanical processing may impact graft efficacy. The characterization of the rheological properties and structure of different fat derivatives in this study may help surgeons select the better type of tissue for a given intervention; however, further studies are still required.

Influences of blood flow parameters on temperature distribution during liver tumor microwave ablation.

Highlights: (1) A 3D simulation model of MWA (microwave ablation) based on the temperature-dependent characteristic parameters and blood flow parameters was established to realize the visual simulation of temperature distribution and coagulation zone. The internal forced convection condition was used to accurately characterize the large vessel. (2) The ex vivo MWA experimental platform was built to verify the accuracy of the simulation model. A peristaltic pump was employed for operatively controlling blood circulation and a medical soft plastic tube was introduced for appropriately simulating a blood vessel. (3) The influences of blood flow parameters of large vessels on temperature distribution and coagulation zone were systematically analyzed in order to provide reference and guidance for MWA clinicians. Purpose: Clinical MWA of liver tumor is significantly limited by the accurate prediction of vascular cooling effects. To provide reference and guidance for clinical MWA of liver tumor, the three-dimensional effects of different blood flow parameters of large vessels on MWA temperature distribution were systematically evaluated. Materials and methods: Firstly, the MWA three-dimensional finite element simulation model with blood flow parameters was established. Secondly, to verify the effectiveness of the model, MWA was performed ex vivo in porcine liver for 360 s and the temperature was measured by thermocouples. A medical soft plastic tube was placed parallel to the MWA antenna to simulate a natural liver vessel. Finally, based on this model, the influences of different vessel diameters and vessel-antenna spacings on MWA temperature distribution were analyzed. Results: Sixteen ablations were performed to verify the accuracy of the simulation model. The mean temperature errors between measured data and simulation results at six measurement points were 3.87 ℃. In the first 10 seconds of MWA, the vessel cooling effect on temperature distribution was negligible. When the vessel-antenna spacing was 5 mm and the vessel diameter varied from 3 mm to 6 mm, the temperature at the measured point near the vessel decreased by 2.11 ℃ at 360 s. When the vessel diameter was 6 mm and the vessel-antenna spacing varied from 5 mm to 7 mm, the temperature at the measured point near the vessel reduced by 14.91 ℃ at 360 s. In addition, blood diameter had little influence on the temperature distribution near the heating point. The volume of coagulation zone will not be obviously affected once the vessel lies outside the predicted coagulation zone. Conclusions: The MWA simulation model with blood flow parameters is established. Vessel-antenna spacing is the primary factor affecting the temperature distribution. A vessel with larger diameter can have a more significant effect on the temperature distribution. The large vessel will take away and block part of conduction heat, so the coagulation zone will not be formed on the lateral side of the vessel.

Targeting PARP and autophagy evoked synergistic lethality in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), one of the most lethal malignancies worldwide, has limited efficient therapeutic options. Here, we first demonstrated that simultaneously targeting poly (ADP-ribose) polymerase (PARP) and autophagy could evoke striking synergistic lethality in HCC cells. Specifically, we found that the PARP inhibitor Niraparib induced cytotoxicity accompanied by significant autophagy formation and autophagic flux in HCC cells. Further experiments showed that Niraparib induced suppression of the Akt/mTOR pathway and activation of the Erk1/2 cascade, two typical signaling pathways related to autophagy. In addition, the accumulation of reactive oxygen species was triggered, which was involved in Niraparib-induced autophagy. Blocking autophagy by chloroquine (CQ) in combination with Niraparib further enhanced cytotoxicity, induced apoptosis and inhibited colony formation in HCC cells. Synergistic inhibition was also observed in Huh7 xenografts in vivo. Mechanistically, we showed that autophagy inhibition abrogated Niraparib-induced cell-cycle arrest and checkpoint activation. Cotreatment with CQ and Niraparib promoted the formation of γ-H2AX foci while inhibiting the recruitment of the homologous recombination repair protein RAD51 to double-strand break sites. Thus, the present study developed a novel promising strategy for the management of HCC in the clinic and highlighted a potential approach to expand the application of PARP inhibitors.

Conformal coverage of liver tumors by the thermal coagulation zone in 2450-MHz microwave ablation.

Purpose: To optimize treatment schemes using 2450-MHz microwave ablation (MWA), a novel conformal coverage method based on bipolar-angle mapping is proposed that determines whether a liver tumor is completely encompassed by thermal coagulation zones. Materials and methods: Firstly, three-dimensional (3-D) triangular mesh data of liver tumors were reconstructed from clinical computed tomography (CT) slices using the Marching cubes (MC) algorithm. Secondly, characterization models of thermal coagulation zones were established based on finite element simulation results of 40, 45, 50, 55, and 60 W ablations. Finally, coagulation zone models and tumor surface data were mapped and fused on a two-dimensional (2-D) plane to achieve conformal coverage of liver tumors by comparing the corresponding polar radii. Results: Optimal parameters for ablation treatment of liver tumors were efficiently obtained with the proposed conformal coverage method. Fifteen liver tumors were obtained with maximal diameters of 12.329-78.612 mm (mean ± standard deviation, 39.094 ± 19.447 mm). The insertion positions and orientations of the MWA antenna were determined based on 3-D reconstruction results of these tumors. The ablation patterns and durations of tumors were planned according to the minimum mean standard deviations between the ablative margin and tumor surface. Conclusion: The proposed method can be applied to computer-assisted MWA treatment planning of liver tumors, and is expected to guide clinical procedures in future.

Greenhouse gas emissions from synthetic nitrogen manufacture and fertilization for main upland crops in China.

BACKGROUND: A significant source of greenhouse gas (GHG) emissions comes from the manufacture of synthetic nitrogen (N) fertilizers consumed in crop production processes. And the application of synthetic N fertilizers is recognized as the most important factor contributing to direct N2O emissions from agricultural soils. Based on statistical data and relevant literature, the GHG emissions associated with synthetic N manufacture and fertilization for wheat and maize in different provinces and agricultural regions of China were quantitatively evaluated in the present study. RESULTS: During the 2015-2017 period, the average application rates of synthetic N for wheat and maize in upland fields of China were 222 and 197 kg ha-1, respectively. The total consumption of synthetic N on wheat and maize was 12.63 Mt year-1. At the national scale, the GHG emissions associated with the manufacture of synthetic N fertilizers were estimated to be 41.44 and 59.71 Mt CO2-eq year-1 for wheat and maize in China, respectively. And the direct N2O emissions derived from synthetic N fertilization were estimated to be 35.82 and 69.44 Gg N2O year-1 for wheat and maize, respectively. In the main wheat-cultivating regions of China, area-scaled GHG emissions were higher for Inner Mongolia, Jiangsu and Xinjiang provinces. And for maize, Gansu, Xinjiang, Yunnan, Shannxi and Jiangsu provinces had higher area-scaled GHG emissions. Higher yield-scaled GHG emissions for wheat and maize mainly occured in Yunnan and Gansu provinces. CONCLUSIONS: The manufacture and application of synthetic N fertilizers for wheat and maize in Chinese croplands is an important source of agricultural GHG emissions. The current study could provide a scientific basis for establishing an inventory of upland GHG emissions in China and developing appropriate mitigation strategies.

Combined nitrogen fertilizer and wheat straw increases the cadmium phytoextraction efficiency of Tagetes patula.

The soil cadmium (Cd) availability and uptake by Tagetes patula grown in two soil types contaminated with Cd and amended with N fertilizer and wheat straw were studied in a pot-culture experiment. The results indicated that N fertilizer treatment (N) and N fertilizer plus straw treatment (NS) promoted T. patula growth, while straw treatment (S) decreased T. patula biomass relative to the control. NS and S treatments increased Cd mobility in the soil and facilitated its uptake by T. patula in Acidic Ferralsols (AF) and Calcaric Cambisols (CC), but the promotion effect was much greater in CC than in AF. The Cd concentrations in the Tagetes shoots in the S and NS treatments were 40% and 27% greater, respectively, than those in the control treatment for AF, and 111% and 80% greater, respectively, for CC. Decreases in soil pH and increases in dissoluble organic carbon concentration after adding N fertilizer and straw were associated with an increase in soil Cd availability and in Cd uptake by T. patula. The results indicate that the NS treatment can alter the soil microenvironment, increasing Cd bioavailability and thus facilitating Cd uptake by T. patula. This work highlights that the combined application of N fertilizer with straw may be a useful way to increase the phytoextraction efficiency of Cd-contaminated soil by the Cd-hyperaccumulator T. patula.

RF ablation thermal simulation model: Parameter sensitivity analysis.

OBJECTIVE: The aim of the research is to obtain the relative influences of some critical electro-thermal parameters on the ablation temperature and lesion volume during temperature-controlled radiofrequency ablation (RFA) of liver tumor by parameter sensitivity analysis. METHODS: The finite element method (FEM) has been used to establish the simulation model of RFA temperature field, and the sensitivity of the tissue parameters has been analyzed. The effects of six parameters have been taken into account, including the thermal specific capacity (Cp), the thermal conductivity (k), the electrical conductivity (Sigma), the density (rho), the dielectric constant (Epsilon) and the resistance (R). The simulation processes based on different parameter values have been accomplished with Comsol Multiphysics software, and the sensitivity parameters have been obtained utilizing the variance contribution rate (SS%) or the main effects. RESULTS: It was found that the ablation temperature and lesion volume increased with increasing the values of Rand Sigma, but was a reverse situation for Cp and rho. Besides, the influence of k on ablation volume was relatively small and Epsilon had a negligible effect on ablation temperature. CONCLUSIONS: It is concluded that these parameter sensitivity results can provide scientific and reliable reference for the specificity analysis of the RF ablation models.

Temperature simulation of microwave ablation based on improved specific absorption rate method compared to phantom measurements.

PURPOSE: To propose an improved specific absorption rate (SAR) computation method by incorporating a thermal conductivity item, develop mathematical simulation models based on the SAR, and enhance the accuracy of temperature simulation for 2450-MHz microwave fields. MATERIALS AND METHODS: Experimental data of 2450-MHz microwave antenna were obtained with a phantom and then new SAR equations were calculated according to Pennes bio-heat transfer equation. Next, the SAR equations were regarded as heating sources and SAR-derived temperature changes were simulated numerically; Finally, temperature measurement results were compared with simulation data to validate the accuracy of the new SAR method. RESULTS: The simulated and measured temperature changes were generally in good agreement for the phantom. According to comparison results, the maximum error was less than 6 °C, the average error was less than 2 °C, and the standard deviation was less than 1 °C. CONCLUSIONS: This new SAR-derived simulation method can significantly simplify the simulation process and improve the prediction accuracy of microwave ablation temperature field.

Methanolic Extract of Pien Tze Huang Induces Apoptosis Signaling in Human Osteosarcoma MG63 Cells via Multiple Pathways.

Pien Tze Huang (PZH) is a well-known traditional Chinese formulation and has long been used as an alternative remedy for cancers in China and Southeast Asia. Recently, antitumor activity of PZH on several tumors have been increasingly reported, but its antitumor activity and the possible action mechanism on osteosarcoma remains unclear. After treatment with PZH, cell viability of MG-63 cells was dose-dependently inhibited compared to control cells. Moreover, a DNA ladder characteristic of apoptosis was observed in the cells treated with PZH, especially 500 µg/mL, 750 µg/mL. Further investigation showed that PZH treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and Bcl-xL expression. In addition, our results suggested that PZH activated PI3K/Akt signal pathway, and the phosphorylation of Akt and ERK1/2 were associated with the induction of apoptotic signaling. These results revealed that PZH possesses antitumoral activity on human osteosarcoma MG63 cells by manipulating apoptotic signaling and multiple pathways. It is suggested that PZH alone or combined with regular antitumor drugs may be beneficial as osteosarcoma treatments.

Al(3+) -promoted fluoride accumulation in tea plants (Camellia sinensis) was inhibited by an anion channel inhibitor DIDS.

BACKGROUND: Generally, tea plants are grown in acid soil which is rich in aluminum (Al) and fluoride (F). A recent publication showed that pretreatment with Al(3+) promoted F accumulation in tea plants by increasing endogenous Ca(2+) and calmodulin (CaM). A high level of F in tea leaves not only impairs tea quality but also might pose a health risk for people drinking tea regularly. Therefore it is important to try to find some clues which might be beneficial in controlling F accumulation in tea plants grown in acid soil (Al(3+) ). RESULTS: It was found that diisothiocyanostilbene-2,2-disulfonic acid (DIDS) significantly reduced Al(3+) -promoted F accumulation in tea plants. Additionally, Al(3+) plus DIDS treatment stimulated significantly higher Ca(2+) efflux and decreased the CaM level in tea roots compared with Al(3+) treatment. Besides, significantly higher depolarization of membrane potential was shown in tea roots treated with Al(3+) plus DIDS than in those treated with Al(3+) , as well as higher net total H(+) efflux and plasma membrane H(+) -ATPase activity. CONCLUSION: Al(3+) -promoted F accumulation in tea plants was inhibited by an anion channel inhibitor DIDS. Ca(2+) /CaM and membrane potential depolarization may be the components involved in this process. © 2016 Society of Chemical Industry.

Inhibition of autophagy overcomes the nanotoxicity elicited by cadmium-based quantum dots.

Cadmium-based quantum dots (QDs) have shown their values in disease diagnosis, cellular and molecular tracking, small-animal imaging, and therapeutic drug delivery. However, the potential safety problems of QDs, mainly due to their nanotoxicities by unclear mechanisms, have greatly limited its applications. To reverse this situation, we investigated the underlying biological mechanisms of the toxicity of Quantum Dots CdTe/CdS 655 (QDs 655) in this work. QDs 655 was found to elicit nanotoxicity in vitro and in vivo. During the process, autophagy was activated, which was characterized by three main stages of autophagic flux including formation of autophagosomes, lysosomes fused with autophagosomes, and degradation of autophagosomes by lysosomes. Furthermore, the autophagic cell death was demonstrated in vitro under QDs 655 treatment while inhibition of autophagy by pharmacological inhibitors or genetic approaches could attenuate the toxicity induced by QDs 655 in vitro and in vivo. These results indicated that autophagic flux and autophagic cell death were triggered by QDs 655, which elucidated the critical role of autophagy in QDs 655 induced toxicity. Our data may suggest the approach to overcome the toxicity of QDs and other nanoparticles by autophagy inhibition.

Simulation of temperature field for temperature-controlled radio frequency ablation using a hyperbolic bioheat equation and temperature-varied voltage calibration: a liver-mimicking phantom study.

This study aims at improving the accuracy of temperature simulation for temperature-controlled radio frequency ablation (RFA). We proposed a new voltage-calibration method in the simulation and investigated the feasibility of a hyperbolic bioheat equation (HBE) in the RFA simulation with longer durations and higher power. A total of 40 RFA experiments was conducted in a liver-mimicking phantom. Four mathematical models with multipolar electrodes were developed by the finite element method in COMSOL software: HBE with/without voltage calibration, and the Pennes bioheat equation (PBE) with/without voltage calibration. The temperature-varied voltage calibration used in the simulation was calculated from an experimental power output and temperature-dependent resistance of liver tissue. We employed the HBE in simulation by considering the delay time τ of 16 s. First, for simulations by each kind of bioheat equation (PBE or HBE), we compared the differences between the temperature-varied voltage-calibration and the fixed-voltage values used in the simulations. Then, the comparisons were conducted between the PBE and the HBE in the simulations with temperature-varied voltage calibration. We verified the simulation results by experimental temperature measurements on nine specific points of the tissue phantom. The results showed that: (1) the proposed voltage-calibration method improved the simulation accuracy of temperature-controlled RFA for both the PBE and the HBE, and (2) for temperature-controlled RFA simulation with the temperature-varied voltage calibration, the HBE method was 0.55 °C more accurate than the PBE method. The proposed temperature-varied voltage calibration may be useful in temperature field simulations of temperature-controlled RFA. Besides, the HBE may be used as an alternative in the simulation of long-duration high-power RFA.

Artemether Exhibits Amoebicidal Activity against Acanthamoeba castellanii through Inhibition of the Serine Biosynthesis Pathway.

Acanthamoeba sp. parasites are the causative agents of Acanthamoeba keratitis, fatal granulomatous amoebic encephalitis, and cutaneous infections. However, there are currently no effective drugs for these organisms. Here, we evaluated the activity of the antimalarial agent artemether against Acanthamoeba castellanii trophozoites and identified potential targets of this agent through a proteomic approach. Artemether exhibited in vitro amoebicidal activity in a time- and dose-dependent manner and induced ultrastructural modification and cell apoptosis. The iTRAQ quantitative proteomic analysis identified 707 proteins that were differentially expressed after artemether treatment. We focused on phosphoglycerate dehydrogenase and phosphoserine aminotransferase in the serine biosynthesis pathway because of their importance to the growth and proliferation of protozoan and cancer cells. The expression of these proteins in Acanthamoeba was validated using quantitative real-time PCR and Western blotting after artemether treatment. The changes in the expression levels of phosphoserine aminotransferase were consistent with those of phosphoglycerate dehydrogenase. Therefore, the downregulation of phosphoserine aminotransferase may be due to the downregulation of phosphoglycerate dehydrogenase. Furthermore, exogenous serine might antagonize the activity of artemether against Acanthamoeba trophozoites. These results indicate that the serine biosynthesis pathway is important to amoeba survival and that targeting these enzymes would improve the treatment of Acanthamoeba infections. Artemether may be used as a phosphoglycerate dehydrogenase inhibitor to control or block Acanthamoeba infections.

Apoptosis, necrosis, and autophagy in mouse intestinal damage after 15-Gy whole body irradiation.

Enterocytes die during high-dose radiation exposure in radiation accidents. The modality of cell death has a profound effect on the therapeutic response. The ilea from mice with 15 Gy total body irradiation (TBI) were drawn, morphological features observed by hematoxylin and eosin staining and transmission electron micrographs. The biochemical features of mouse ileum presented with the structure were cleaved Caspase-3 (apoptosis marker), Light Chain 3 (LC3)-I's conversion to LC3-II (autophagy marker) and high mobility group box chromosomal protein 1's secretion (necrosis marker). Then, the autophagy inhibitor (3-methyladenine), caspase inhibitor (Z-VAD-FMK) or necrosis inhibitor (necrostatin) was used to prevent death. Apoptosis, autophagy and necrosis were all appeared in the ileum, but necrosis had the biggest size; the use of 3-methyladenine and Z-VAD-FMK prolong one day's life of the mice after 15 Gy TBI, necrostatin significantly extended the lifespan of 15 Gy irradiated mice (p < 0.05). The results suggest that the death of enterocytes could not be classified into one type of cell death but rather as 'mixed death.'

Tyrosine kinase inhibitor Thiotanib targets Bcr-Abl and induces apoptosis and autophagy in human chronic myeloid leukemia cells.

Chronic myeloid leukemia (CML) is characterized by abnormal Bcr and Abl genes and enhanced tyrosine kinase activity. Anti-CML therapy has been much improved along with the applications of tyrosine kinase inhibitors (TKIs) which selectively target Bcr-Abl and have a cytotoxic effect on CML. Recently, four-membered heterocycles as "compact modules" have attracted much interest in drug discovery. Grafting these small four-membered heterocycles onto a molecular scaffold could probably provide compounds that retain notable activity and populate chemical space otherwise not previously accessed. Accordingly, a novel TKI, Thiotanib, has been designed and synthesized. It selectively targets Bcr-Abl, inducing growth inhibition, cell cycle arrest, and apoptosis of CML cells. Meanwhile, the compound Thiotanib could also induce autophagy in CML cells. Interestingly, inhibition of autophagy promotes Thiotanib-induced apoptosis with no further activation of caspase 3, while inhibition of caspases did not affect the cell survival of CML cells. Moreover, the compound Thiotanib could inhibit phosphorylation of Akt and mTOR, increase beclin-1 and Vps34, and block the formation of the Bcl-2 and Beclin-1 complex. This indicates the probable pathway of autophagy initiation. Our results highlight a new approach for TKI reforming and further provide an indication of the efficacy enhancement of TKIs in combination with autophagy inhibitors.