Economic tolerance design of the P2 raceway based on the quasi-static model of aerospace ball bearings.

This study focused on designing the raceway tolerance of high-precision rolling bearings. After the tolerance error equivalence relationship is defined, the application of the rolling bearing error equalization effect in tolerance design is studied. First, a five-degree of freedom quasi-static model was established for angular contact ball bearings. The waviness was included in the manufacturing error, and the radial and axial runouts of the bearing inner ring were calculated. Second, the error homogenization effect of the rolling bearing was studied, and the error homogenization coefficient was defined. The results of the study demonstrated that the bearing rotary accuracy was higher than the raceway error by an order of magnitude. Third, the manufacturing error range of each precision grade of the rolling bearing raceway was obtained by investigating errors of the equalization coefficient. Finally, the specific value of the raceway tolerance of P2 rolling bearings was obtained.

Multidimensional Study on the Wear of High-Speed, High-Temperature, Heavy-Load Bearings.

The friction and wear performance of high-performance bearings directly affects the accuracy and maneuverability of weapons and equipment. In this study, high-speed, high-temperature, and heavy-load durability experiments of weapon bearings were carried out, and their wear properties (i.e., surface wear, metamorphic layer, scanning electron microscopy/energy-dispersive spectroscopy (SEM/EDS), residual stress, and retained austenite) were analyzed in multiple dimensions. The results showed the following: (1) The experimental temperature of the serviced front-end bearing is always lower than that of the rear bearing. (2) The metamorphic layer of the serviced rear bearing (i.e., inner ring, outer ring, rolling body, and cage) > the metamorphic layer of the serviced front-end bearing > the metamorphic layer of the unserviced bearing. (3) The rolling body of the rear bearing at high experimental temperatures contains not only elemental O, but also elemental P and Sr. (4) In the EDS analysis of the rolling elements, with the migration from the "ball edge" to the "ball center", the elemental C in the rolling elements of serviced or unserviced bearings decreases slowly, while the elemental Fe content increases slowly.

Parthenolide and arsenic trioxide co-trigger autophagy-accompanied apoptosis in hepatocellular carcinoma cells.

Although arsenic trioxide (ATO) shows a strong anti-tumor effect in the treatment of acute promyelocytic leukemia, it does not benefit patients with hepatocellular carcinoma (HCC). Thus, combination therapy is proposed to enhance the efficacy of ATO. Parthenolide (PTL), a natural compound, selectively eradicates cancer cells and cancer stem cells with no toxicity to normal cells. In this study, we chose PTL and ATO in combination and found that nontoxic dosage of PTL and ATO co-treatment can synergistically inhibit the in vitro and in vivo proliferation activity of HCC cells through suppressing stemness and self-renewal ability and inducing mitochondria-dependent apoptosis. More importantly, USP7-HUWE1-p53 pathway is involved in PTL enhancing ATO-induced apoptosis of HCC cell lines. Meanwhile, accompanied by induction of apoptosis, PTL and ATO evoke autophagic activity via inhibiting PI3K/Akt/mTOR pathway, and consciously controlling autophagy can improve the anti-HCC efficacy of a combination of PTL and ATO. In short, our conclusion represents a novel promising approach to the treatment of HCC.

Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells.

Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylori, H. pylori culture filtrate (HPCF), and VacA could activate autophagy in a gastric epithelial cell line (GES-1). VacA-caused mitochondrial depolarization retards the import of PINK1 into the damaged mitochondria and evokes mitophagy. And, among mass spectrometry (LC-MS/MS) identified 25 mitochondrial proteins bound with VacA, Tom20, Tom40, and Tom70, TOM complexes responsible for PINK1 import, were further identified as having the ability to bind VacA in vitro using pull-down assay, co-immunoprecipitation, and protein-protein docking. Additionally, we found that the cell membrane protein STOM and the mitochondrial inner membrane protein PGAM5 also interacted with VacA. These findings suggest that VacA captured by STOM forms endosomes to enter cells and target mitochondria. Then, VacA is transported into the mitochondrial membrane space through the TOM complexes, and PGAM5 aids in inserting VacA into the inner mitochondrial membrane to destroy the membrane potential, which promotes PINK1 accumulation and Parkin recruitment to induce mitophagy. This study helps us understand VacA entering mitochondria to induce the mitophagy process.

Predicting the postmortem interval using human intestinal microbiome data and random forest algorithm.

Gradual changes in microbial communities in a human body after death can be used to determine postmortem interval (PMI). In this study, gut microflora samples were collected from the vermiform appendix and the transverse colon of human cadavers with PMIs between 5 and 192 h. The results revealed that the appendix might be an excellent intestinal sampling site and the appendix flora had an inferred succession rule during human body decomposition. Firmicutes, Bacteroidetes, and their respective subclasses showed a predictable successionrule in relative abundance over time. A Random Forest regression model was developed to correlate human gut microbiota with PMI. We believe that our findings have increased the knowledge of the composition and abundance of the gut microbiota in human corpses, and suggest that the use of the human appendix microbial succession may be a potential method for forensic estimation of the time of death.

Suppression Of Aberrant Activation Of NF-κB Pathway In Drug-resistant Leukemia Stem Cells Contributes To Parthenolide-potentiated Reversal Of Drug Resistance In Leukemia.

Although many drugs that targeted the specific features of leukemia stem cells (LSCs) have substantial application in the clinical treatment of leukemia, the LSCs relapsed and caused drug-resistant leukemia. Therefore, it is necessary to identify the unique features of LSCs in relapsing and drug-resistant leukemia and also to explore the drugs that directed at these features. Our clinical data have indicated that relapsed patients with acute myeloid leukemia have more abundant proportion of LSCs with enhanced breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) expression when compared to the untreated patients. The results showed that compared with LSCs derived from sensitive K562 cells, LSCs from drug-resistant K562/ADM cells have much higher chemotherapeutic resistance, and so we termed these cells as "drug-resistant LSCs". Subsequently, aberrant activation of NF-κB pathway in drug-resistant LSCs was further using gene chip analysis. Also, parthenolide (PTL), which is a specific NF-κB inhibitor, effectively eliminated drug-resistant LSCs and enhanced the sensitivity of K562/ADM cells to doxorubicin-induced apoptosis by down-regulating NF-κB pathway-mediated P-gp expression. These findings make the research area of LSCs more abundant and provide a potential therapeutic strategy for the treatment of refractory and relapsed leukemia.

LncRNA MEG3 inhibits the proliferation of neural stem cells after ischemic stroke via the miR-493-5P/MIF axis.

OBJECTIVE: The proliferation of neural stem cells (NSCs1), or lack thereof, can have profound effects on brain tissue remodeling for ischemic stroke (IS2). In this study, we aimed to reveal the influence of the lncRNA MEG3/miR-493-5p/MIF axis on NSC proliferation after IS. METHODS: We established an oxygen glucose-deprivation/reoxygenation (OGD/R3) in vitro model of IS in NSCs. We evaluated NSC isolation efficiency and proliferation by NESTIN, SOX2, and PCNA immunofluorescence staining. MEG3 and miR-493-5P levels were assessed by quantitative real-time polymerase chain reaction (qRT-PCR4). Changes in MIF protein expression levels were analyzed using Western blotting. We then evaluated the role of MEG3 and miR-493-5p by transfection of si-MEG3, a miR-493-5p mimic, or miR-493-5p inhibitor. NSC proliferation was quantified using Cell Counting Kit-8 analysis. RESULTS: NESTIN and SOX2 were co-expressed in endogenous NSCs. Following OGD/R, MEG3 and miR-493-5P were significantly upregulated in NSCs, while MIF levels decreased and proliferation was inhibited. Knockdown of MEG3 inhibited miR-493-5p and rescued expression of MIF and PCNA, restoring cellular proliferation levels. In NSCs transfected with a miR-493-5p mimic or inhibitor, MIF levels were down- or upregulated, respectively. Consistently, transfection of a miR-493-5p mimic reduced NSC proliferation, while transfection with a miR-493-5p inhibitor or si-MEG3 rescued the inhibitory effect of OGD/R on NSC proliferation. After co-transfection of si-MEG3 and a miR-493-5p mimic of OGD/R-induced NSCs, levels of PCNA, an indicator of cellular proliferation, were significantly reduced. Conclusion MEG3 inhibits NSC proliferation of after IS via positive regulation of miR-493-5p and potential subsequent downregulation of MIF.

Research on a Five-Axis Machining Center Worktable with Bionic Honeycomb Lightweight Structure.

The processing of high-precision aerospace parts requires not only ultra-precision machine tools, but also high-efficiency processing. However, in order to realize high-efficiency processing, besides optimizing the system and process parameters, some subversive research can also be done on the machine tool structure. In this paper, the lightweight research is mainly carried out on the structure of machine tool worktable. The traditional workbench is very "heavy" and "slowness". If the traditional workbench is subverted and reformed to reduce the weight, the processing efficiency will be improved qualitatively. Therefore, this paper studies the lightweight worktable of CFRP (carbon fiber reinforced polymer) in combination with the biological "honeycomb" shape. At first, the tensile, bending, compressive and laminar shear analysis of CFRP were carried out, and the comprehensive parameters were obtained. Simultaneously, the theoretical research and the honeycomb structure simulation and verification of CFRP worktable are carried out. The results show that the HACT (honeycomb arrangement of circular tubes) is 18.51% better than the SACT (straight arrangement of circular tubes) and 45.05% better than the OW (original worktable) by comparing and analyzing the weight of the three modes (HACT, SACT and OW). The actual weight of bionic honeycomb lightweight worktable is 1100 kg, while the simulation result is 1080.25 kg, with an error of 1.8%. Meanwhile, it is analyzed that the original workbench weight of the five-axis machining center is 2023 kg, while the simulation result is 1998.6 kg, with an error of 1.2%. The lightweight degree is reduced by 45.05%. However, the actual lightweight degree has been reduced by 45.63%. The error between simulation and actual is less than 1.3%. This kind of structural transformation has brought forward cutting-edge innovations to the machine tool processing industry. It provides a reference scheme for related enterprises in the future equipment renovation.

Live vaccine preserved at room temperature: Preparation and characterization of a freeze-dried classical swine fever virus vaccine.

The heat-stable live-attenuated classical swine fever virus (CSFV) vaccine is an urgent need in many countries of Asia, Europe and Latin America. In this study, the thermostability of lyophilized live-attenuated CSFV vaccine formulations were investigated using accelerated stability at 37 °C for 10 days. The freeze-dried heat-stable formulation ST16, containing excipient combinations of trehalose, glycine, thiourea and phosphate buffer shows the superior thermostability. Moreover, the lyophilized vaccine with formula ST16 kept loss of viral activity less than 0.5 log10 during 24 months at storage temperatures of 2-8 °C. In thermal study, ST16 stabilized the vaccine within 1.0 log10 loss after storage at up to 25 °C for 6 months and room temperature for 7 months. Even under the harshest storage conditions of 37 °C for 25 days and 45 °C for 2 weeks, the virus titer dropped less than 1.0 log10 using ST16. Besides, it is notable that ST16 excluded gelatin and exogenous proteins, which might cause allergic reactions, thus avoiding immune side effects. The vaccine formulated ST16 proved to be safe and effective when immunized to piglets in vivo. The characteristics of dried vaccines were analyzed by X-ray powder diffraction, residual water measurements, differential scanning calorimetry and it was found that vaccine antigen were preserved in an amorphous matrix with high glass transition temperature above 60 °C and low residual water content below 2%, which made the vaccine more stable during storage.

Heteroleptic Ir(iii) complexes with varied π-conjugated diimine ligands: synthesis, tunable triplet states and nonlinear absorption properties.

Four heteroleptic Ir(iii) complexes (Ir-1-Ir-4) with varied π-conjugated diimine ligands were synthesized. Their optical properties were investigated systematically via spectroscopic methods, in order to elucidate the influence of the extended π-conjugation on the singlet and triplet states of the molecules. All these Ir(iii) complexes exhibit ligand localized 1π,π* transitions below 370 nm, and broad metal-to-ligand and ligand-to-ligand charge transfer (MLCT/LLCT) absorption bands in the visible region. Extending the π-conjugation in diimine ligands influences the electron distribution of the triplet state. The 3π,π* dominated Ir(iii) complexes (Ir-3 and Ir-4) exhibit long-lived triplet states and low phosphorescence quantum yields, compared with the charge transfer dominated Ir(iii) complexes (Ir-1 and Ir-2). Complexes Ir-3 and Ir-4 exhibit broadband transient absorption spectra from 420 to 750 nm, between which the nonlinear absorption could be observed by virtue of reverse saturable absorption. The results of nonlinear transmission measurements using 532 nm laser pulses further elucidate that selected complexes Ir-3 and Ir-4 are promising candidates for optical limiting applications.

Synergistic cardiac pathological hypertrophy induced by high-salt diet in IGF-IIRα cardiac-specific transgenic rats.

Stress-induced cardiac hypertrophy leads to heart failure. Our previous studies demonstrate that insulin-like growth factor-II receptor (IGF-IIR) signaling is pivotal to hypertrophy regulation. In this study, we show a novel IGF-IIR alternative spliced transcript, IGF-IIRα (150 kDa) play a key role in high-salt induced hypertrophy mechanisms. Cardiac overexpression of IGF-IIRα and high-salt diet influenced cardiac dysfunction by increasing pathophysiological changes with up-regulation of hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). We found that, cardiac hypertrophy under high-salt conditions were amplified in the presence of IGF-IIRα overexpression. Importantly, high-salt induced angiotensin II type I receptor (AT1R) up regulation mediated IGF-IIR expressions via upstream mitogen activated protein kinase (MAPK)/silent mating type information regulation 2 homolog 1 (SIRT1)/heat shock factor 1 (HSF1) pathway. Further, G-coupled receptors (Gαq) activated calcineurin/nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3)/protein kinase C (PKC) signaling was significantly up regulated under high-salt conditions. All these effects were observed to be dramatically over-regulated in IGF-IIRα transgenic rats fed with a high-salt diet. Altogether, from the findings, we demonstrate that IGF-IIRα plays a crucial role during high-salt conditions leading to synergistic cardiac hypertrophy.

Ebb-and-flow of macroautophagy and chaperone-mediated autophagy in Raji cells induced by starvation and arsenic trioxide.

Autophagy is crucial in the maintenance of homeostasis and regenerated energy of mammalian cells. Macroautophagy and chaperone-mediated autophagy(CMA) are the two best-identified pathways. Recent research has found that in normal cells, decline of macroautophagy is appropriately parallel with activation of CMA. However, whether it is also true in cancer cells has been poorly studied. Here we focused on cross-talk and conversion between macroautophagy and CMA in cultured Burkitt lymphoma Raji cells when facing serum deprivation and exposure to a toxic compound, arsenic trioxide. The results showed that both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of nutrition deprivation, and then gradually decreased to near baseline. With nutrient deprivation persisted, CMA progressively increased along with the decline of macroautophagy. On the other hand, in arsenic trioxide-treated Raji cells, macroautophagy activity was also significantly increased, but CMA activity was not rapidly enhanced until macroautophagy was inhibited by 3-methyladenine, an inhibitor. Together, we conclude that cancer cells exhibit differential responses to diverse stressor-induced damage by autophagy. The sequential switch of the first-aider macroautophagy to the homeostasis-stabilizer CMA, whether active or passive, might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular stressors. These findings must be helpful to understand the characteristics, compensatory mechanisms and answer modes of different autophagic pathways in cancer cells, which might be very important and promising to the development of potential targeting interventions for cancer therapies via regulation of autophagic pathways.

Arsenic trioxide induces autophagy and antitumor effects in Burkitt's lymphoma Raji cells.

Although it is generally acknowledged that auto-phagy plays an important role in tumorigenesis and therapy, studies of autophagy in different cell types and under different conditions have led to conflicting theories regarding the influence of autophagy on cell death. In the present study, we explored the role of autophagy and its underlying mechanism in the inhibitory effects of arsenic trioxide (As2O3) on Burkitt's lymphoma Raji cells. The results showed that As2O3 significantly inhibited the proliferation of Raji cells in a dose- and time-dependent manner, induced G2/M phase cell cycle arrest and apoptosis. Moreover, As2O3 also promoted the formation of autophagic vacuoles, as well as increased the degradation of autophagy substrate P62 protein, which was accompanied by an upregulation of Beclin-1 gene and a downregulation of Bcl-2 gene expression. 3-Methyladenine, an autophagy inhibitor, not only increased cell viability through inhibiting autophagic cell death and apoptosis, but also reversed the upregulation of Beclin-1 gene and the downregulation of Bcl-2 gene in the Raji cells induced by As2O3. These results may lead to a better understanding of the action of As2O3 and may provide evidence that autophagy plays an important role in the regulation of cell death. Therefore, regulation of autophagic activity may be a promising therapy for patients with Burkitt's lymphoma.

Insulin resistance reduces sensitivity to Cis-platinum and promotes adhesion, migration and invasion in HepG2 cells.

The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the instability of HepG2/ IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.

[Apoptosis effects of drug sensitivity leukemia cells induced by nano-realgar].

OBJECTIVE: To explore apoptosis-inducing effects of realgar nanoparticle (nano-realgar) on drug-sensitive leukemia cells. METHOD: Preparation of nano-realgar was mechanical milled using a high-energy planetary ball mill. Using drug-sensitive leukemia cells (K562) as target cells, MTT assay was used to detect the proliferating activity of K562 cells, and the cellular apoptosis was investigated with double staining of FITC-Annexin V and propidium iodide (PI) by flow cytometry. Flow cytometry (FCM) was employed to detect expression of intracellular Bax, Bcl-2, P-53 protein and the activity of Caspase-3. RESULT: The raw realgar was made to ultra-fine powder by ball milling, and the average diameter of the nanoparticle was (72.72 +/- 22.18) nm measured with electron microscopes. Nano-realgar significantly inhibited the proliferation of K562 cells, Treated for 24, 48 and 72 hours, the 50% inhibitory concentration (IC50) was 43.48, 20.52, 16.07 mg x L(-1). After exposure to 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 hours, the apoptosis of K562 cells detected by Annexin V/PI staining was increased, the apoptotic rate of K562 cells was 10. 52% and 73.25%. After the target cells were treated with 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the expression of P-53, Bax, Bcl-2 markedly increased in a time and dose-dependent manner. After administration of 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the percentage of BCRP+, P-gp+ and co-expressing P-gp and BCRP cell population in K562 cells incrased dramatically. CONCLUSION: Nano-Realgar significantly induced apoptosis of drug-sensitive leukemia cells.

Acquired multidrug resistance in human K562/ADM cells is associated with enhanced autophagy.

Autophagy, as a necessary process for survival in mammalian cells deprived of nutrients or growth factors, will be activated in many tumor cells while treated with chemotherapeutic drugs, but the role of autophagy in acquired multidrug resistance of human acute myelogenous leukemia to adriamycin-based chemotherapy remains to be clarified. Our aim was to address that question by surveying the autophagic activity in parental acute myelogenous leukemia cell line K562 and resistant sub cell line, K562/ADM, which were obtained by treating adriamycin with increasing concentrations. K562/ADM and K562 cells were exposed to PBS culture medium for 3 hours, then the stress-induced autophagy was measured. Real-time quantitative RT-PCR revealed the expression of LC3 mRNA was higher in K562/ADM than in K562 cells. LC3-II, as an autophagosomal marker, was more abundant in K562/ADM than in K562 cells measured by Western blotting. To determine the effect of 3-MA, a known specific inhibitor of autophagy, on overcoming acquired multidrug resistance induced by adriamycin, the MTT assay and flow cytometry were performed. We also found that 3-MA can enhance the growth inhibition and apoptotic effect of adriamycin in acquired resistant cells (K562/ADM). Collectively, our results provide evidence that the upregulation of autophagy plays a major role in multidrug resistance of K562/ADM cells induced by adriamycin.

[Genetic characterization of human parainfluenza virus 3 circulating in Gansu and Shaanxi Provinces from 2009 to 2011].

To investigate the genetic characterization of Human parainfluenza virus-3 (HPIV-3) circulating in Gansu and Shaanxi Provinces of China, 719 throat swabs were collected from pediatric patients with acute respiratory infections from 2009-2011. Multiplex RT-PCR was used to screen common respiratory viral pathogens. For HPIV-3-positive specimens, nested RT-PCR was used to amplify the HN gene of HPIV-3. The nucleotides of Hemagglutinin-neuraminidase(HN)gene of 13 HPIV-3 positive strains identified in Gansu and Shaanxi Provinces were successfully sequenced and compared with those downloaded from GenBank. The phylogenetic analysis based on the nucleotides sequence of HN gene showed that 13 HPIV-3 strains belonged to sub-cluster C3 with little sequence variation (overall nucleotide divergence of 0.2%-2.3% and amino acid divergence at 0-1.1%). Compared with the complete gene of HPIV-3 strains from U.S.A., Canada, and Australia, the biggest divergence of the nucleotide and amino acid lovels was 6.0% and 3.4%, respectively. The nucleotide divergence between shaanxi09-2 and shaanxi10-H0091 was 0.9%, while the nucleotide divergence between shaanxi10-H005 and gansull-62110372 was 0.5%, between shaanxi09-2 and BJ/291/09 was 0.6%. However, there was no amino acid divergence among them. It is likely that HPIV-3 virus had been transmitting in Gansu and Shaanxi Provinces for several years. Human parainfluenza virus-3 (HPIV-3) circulated in Gansu and Shaanxi Provinces from 2009 to 2011 belonged to sub-cluster C3.

[Surveillance and forecast of schistosomiasis based on sentinel mouse technique in key water regions of Wuhan City in 2011].

OBJECTIVE: To understand the water infectivity of schistosome in key water regions of Wuhan City and explore the role of a sentinel mouse technique on surveillance and forecast system for schistosomiasis. METHODS: Schistosome-endemic areas of the Yangtze River, the Dongjing-Tongshun River system, the Fu-Lun River system and the Jinshui River of Wuhan City were chosen as the surveillance and forecast sites. The Oncomelania snail distribution and infection were surveyed before the flood season. The water infectivity was detected by using the sentinel mouse technique during the flood season. The infection status of people in the villages around the surveillance sites and the activities of human beings and domestic animals were surveyed. The correlation between the infection rate of sentinel mice and snail status was tested by the rank correlation method. The emergency response mechanism was initiated when the areas with schistosomes were detected in water. RESULTS: Among the 18 surveillance sites, 15 sites with infected sentinel mice were found, accounting for 83.33%. A total of 554 sentinel mice were placed and 540 recovered, with a recovery rate of 97.47%. All the recovered mice were dissected and 75 infected, with a total infection rate of 13.89%. Totally 172 adult worms were collected, with mean worm burden of 2.29 +/- 0.71 worms per mouse. The infection rates of sentinel mice in 4 water systems were 8.33%, 24.53%, 10.85% and 6.56%, respectively, and the mean worm burdens of infected sentinel mice were 2.33 +/- 0.71, 2.28 +/- 0.76, 2.22 +/- 0.60 and 2.75 +/- 0.96 worms per mouse, respectively. The infection rates of sentinel mice in 4 water systems had a statistically significant difference (chi2 = 19.131, P = 0.000). The mean worm burdens of the infected sentinel mice in 4 water systems had no statistically significant difference (F = 0.638, P = 0.593). The correlation coefficient among the infection rate of sentinel mice, snail area, the average density of living snails and infected snail rate had no statistical significance. Among the 15 sites with infected sentinel mice, 8 sites with fisherman activities, 8 sites with anglers or planters, 10 sites with cattle keepings and 4 of which with infected cattle. All the 15 sites with cercariae-infected water bodies started the emergency response and no epidemic situation happened. CONCLUSIONS: The water infectivity of schistosome in key water regions of Wuhan City was relatively high. Detecting water infectivity based on a sentinel mouse technique is an important part of surveillance and forecast system for schistosomiasis.

Antitumor effect of arsenic trioxide in human K562 and K562/ADM cells by autophagy.

Arsenic trioxide (As(2)O(3)) has been reported to have potent antitumor effects in vitro and in vivo by inducing cell death via cell cycle arrest and apoptosis in leukemia cells, but the mechanisms of As(2)O(3)-mediated cell death are not fully understood. In this study, we provided in vitro evidence that As(2)O(3) was a potent inducer of autophagy in leukemia K562 and its drug-resistant line K562/ADM cells. As(2)O(3) significantly activated autophagic cell death (programmed cell death type II) in leukemia cell lines. Numerous large cytoplasmic inclusions, abundant autophagic vacuoles, phagocytizing cytoplasm and organelles were observed in As(2)O(3)-treated cells using electron microscope. MDC-labeled autophagic vacuoles were observed by fluorescent inverted phase contrast microscopy and the enhanced MDC fluorescent staining was detected by flow cytometry in As(2)O(3)-treated cells. Furthermore, real-time quantitative RT-PCR revealed that the expression levels of Beclin-1 and LC3 genes, which play key roles in autophagy, increased in As(2)O(3) treated samples than in controls, indicating that autophagy can potentially be involved in the antitumor properties of As(2)O(3). The expression level of Bcl-2 gene, an anti-apoptotic molecule, decreased in As(2)O(3) treated samples than in controls, suggesting that Bcl-2 may be involved in accumulating Beclin-1 and triggering autophagic cell death in As(2)O(3)-treated leukemia cells. Western blotting also showed that As(2)O(3) up-regulated Beclin-1. Altogether, our data provide direct evidence that autophagic cell death is critical for the effects of As(2)O(3) on acute myelogenous leukemia cells.

Inhibition of thioredoxin reductase by auranofin induces apoptosis in adriamycin-resistant human K562 chronic myeloid leukemia cells.

Mammalian thioredoxin reductase (TrxR) catalyzes the NADPH-dependent reduction of oxidized thioredoxin (Trx) and plays a central role in regulating cellular redox homeostasis, cell growth and apoptosis. Increasing evidence shows that TrxR is over-expressed or constitutively active in many tumor cells. Moreover, TrxR appears to contribute to increased tumor cell growth and a resistance to chemotherapy. In this study, we evaluated the activity of TrxR in adriamycin-resistant leukemic cells (K562/ADM) and adriamycin-sensitive parental lines (K562), and found that TrxR activity was higher in the drug resistant cell sublines K562/ADM than in K562 drug sensitive parental cells. Auranofin, a gold(I) compound clinically used as an antirheumatic agent, reduced TrxR activity and was more effective than adriamycin in decreasing cell viability in K562/ADM cells. In addition, auranofin induced apoptosis in dose-dependent manners, accompanied by caspase-3 activation in K562/ADM cells. Our results demonstrate that inhibition of TrxR and induction of apoptosis by auranofin provides its ability in overcoming adriamycin resistance in K562/ADM cells.