Altered temporoparietal junction activity during reflected self-evaluation in sub-clinical depression.

Negative self-schema is a core symptom of depression. According to social psychological theories, two types of self-evaluations play important roles in forming the negative self-view: direct self-evaluation (that is, evaluating the self directly through one's first-person perspective introspection) and reflected self-evaluation (which requires theory of mind (ToM) ability, and is evaluating the self through reflecting on a third person's perspective). Although many previous studies have investigated the processing of the direct self-evaluation in depression, few have extended research on the reflected self-evaluation. In the current study, functional magnetic resonance imaging scans were acquired in 26 dysphoric (individuals with elevated number of depressive symptoms) and 28 control participants during both direct and reflected self-evaluation tasks. Two regions of interest were defined within bilateral temporoparietal junctions (TPJs) because their significant role in ToM. Results showed that the dysphoric participants evaluated themselves more negatively than the control participants, regardless of whose perspective they were taking. More importantly, the enhanced TPJs' activations were observed in the control group during the reflected self-evaluation task versus the direct self-evaluation task, whereas no such difference was observed in the dysphoric participants. The results are interpreted in the framework of impaired ToM ability in sub-clinical depression.  General Scientific Summary (GSS) Negative self-schema is one of the core symptoms of depression. This study suggests that the negative self-schema reflects not only in direct self-evaluation (i.e. evaluating the self via one's own introspection) but also in reflected self-evaluation (i.e. evaluating the self via others' perspective). Importantly, altered TPJ activity was found during a reflected self-evaluation task among individuals with depressive symptoms. These changes in brain function might be associated with impaired ToM ability in sub-clinical depression.

1000 °C High-Temperature Wetting Behaviors of Molten Metals on Laser-Microstructured Metal Surfaces.

The melting of metals at high temperatures is common and important in many fields, e.g., metallurgy, refining, casting, welding, brazing, even newly developed batteries, and nuclear fusion, which is thus of great value in modern industrialization. However, the knowledge of the wetting behaviors of molten metals on various substrate surfaces remains insufficient, especially when the temperature is over 1000 °C and with microstructured metal substrate surfaces. Herein, we selected molten cerium (Ce) on a tantalum (Ta) substrate as an example and investigated in detail its wetting at temperatures up to 1000 °C by modulating the microstructures of the substrate surfaces via laser processing. We discovered that the wetting states of molten Ce on Ta surfaces at temperatures over 900 °C could be completely altered by modifying the laser-induced surface microstructures and the surface compositions. The molten Ce turned superlyophilic with its contact angle (CA) below 10° on the only laser-microstructured surfaces, while it exhibited lyophobicity with a CA of about 135° on the laser-microstructured plus oxidized ones, which demonstrated remarkably enhanced resistance against the melt with only tiny adhesion in this circumstance. In contrast, the CA of molten Ce on Ta substrate surfaces only changed from ∼25 to ∼95° after oxidization without laser microstructuring. We proved that modulating the substrate surface microstructures via laser together with oxidization was capable of efficiently controlling various molten metals' wetting behaviors even at very high temperatures. These findings not only enrich the understanding of molten metal high-temperature wettability but also enable a novel practical approach to control the wetting states for relevant applications.

A nomogram for predicting the mortality of patients with type 2 diabetes mellitus complicated with acute kidney injury in the intensive care unit.

BACKGROUND: There is no predictive tool for type 2 diabetes mellitus (T2DM) patients with acute kidney injury (AKI). Our study aimed to establish an effective nomogram model for predicting mortality in T2DM patients with AKI. METHOD: Data on T2DM patients with AKI were obtained from the Medical Information Mart for Intensive Care III. 70% and 30% of the patients were randomly selected as the training and validation cohorts, respectively. Univariate and multivariate logistic regression analyses were used to identify factors associated with death in T2DM patients with AKI. Factors significantly associated with survival outcomes were used to construct a nomogram predicting 90-day mortality. The nomogram effect was evaluated by receiver operating characteristic curve analysis, Hosmer‒Lemeshow test, calibration curve, and decision curve analysis (DCA). RESULTS: There were 4375 patients in the training cohort and 1879 in the validation cohort. Multivariate logistic regression analysis showed that age, BMI, chronic heart failure, coronary artery disease, malignancy, stages of AKI, white blood cell count, blood urea nitrogen, arterial partial pressure of oxygen and partial thromboplastin time were independent predictors of patient survival. The results showed that the nomogram had a higher area under the curve value than the sequential organ failure assessment score and simplified acute physiology score II. The Hosmer‒Lemeshow test and calibration curve suggested that the nomogram had a good calibration effect. The DCA curve showed that the nomogram model had good clinical application value. CONCLUSION: The nomogram model accurately predicted 90-day mortality in T2DM patients with AKI. It may provide assistance for clinical decision-making and treatment, thereby reducing the medical burden.

Discovering hidden brain network responses to naturalistic stimuli via tensor component analysis of multi-subject fMRI data.

The study of brain network interactions during naturalistic stimuli facilitates a deeper understanding of human brain function. To estimate large-scale brain networks evoked with naturalistic stimuli, a tensor component analysis (TCA) based framework was used to characterize shared spatio-temporal patterns across subjects in a purely data-driven manner. In this framework, a third-order tensor is constructed from the timeseries extracted from all brain regions from a given parcellation, for all participants, with modes of the tensor corresponding to spatial distribution, time series and participants. TCA then reveals spatially and temporally shared components, i.e., evoked networks with the naturalistic stimuli, their time courses of activity and subject loadings of each component. To enhance the reproducibility of the estimation with the adaptive TCA algorithm, a novel spectral clustering method, tensor spectral clustering, was proposed and applied to evaluate the stability of the TCA algorithm. We demonstrated the effectiveness of the proposed framework via simulations and real fMRI data collected during a motor task with a traditional fMRI study design. We also applied the proposed framework to fMRI data collected during passive movie watching to illustrate how reproducible brain networks are evoked by naturalistic movie viewing.

An efficient functional magnetic resonance imaging data reduction strategy using neighborhood preserving embedding algorithm.

High dimensionality data have become common in neuroimaging fields, especially group-level functional magnetic resonance imaging (fMRI) datasets. fMRI connectivity analysis is a widely used, powerful technique for studying functional brain networks to probe underlying mechanisms of brain function and neuropsychological disorders. However, data-driven technique like independent components analysis (ICA), can yield unstable and inconsistent results, confounding the true effects of interest and hindering the understanding of brain functionality and connectivity. A key contributing factor to this instability is the information loss that occurs during fMRI data reduction. Data reduction of high dimensionality fMRI data in the temporal domain to identify the important information within group datasets is necessary for such analyses and is crucial to ensure the accuracy and stability of the outputs. In this study, we describe an fMRI data reduction strategy based on an adapted neighborhood preserving embedding (NPE) algorithm. Both simulated and real data results indicate that, compared with the widely used data reduction method, principal component analysis, the NPE-based data reduction method (a) shows superior performance on efficient data reduction, while enhancing group-level information, (b) develops a unique stratagem for selecting components based on an adjacency graph of eigenvectors, (c) generates more reliable and reproducible brain networks under different model orders when the outputs of NPE are used for ICA, (d) is more sensitive to revealing task-evoked activation for task fMRI, and (e) is extremely attractive and powerful for the increasingly popular fast fMRI and very large datasets.

Two effective clinical prediction models to screen for obstructive sleep apnoea based on body mass index and other parameters.

BACKGROUND AND OBJECTIVE: The diagnosis of obstructive sleep apnea (OSA) relies on polysomnography which is time-consuming and expensive. We therefore aimed to develop two simple, non-invasive models to screen adults for OSA. METHODS: The effectiveness of using body mass index (BMI) and a new visual prediction model to screen for OSA was evaluated using a development set (1769 participants) and confirmed using an independent validation set (642 participants). RESULTS: Based on the development set, the best BMI cut-off value for diagnosing OSA was 26.45 kg/m2, with an area under the curve (AUC) of 0.7213 (95% confidence interval (CI), 0.6861-0.7566), a sensitivity of 57% and a specificity of 78%. Through forward conditional logistic regression analysis using a stepwise selection model developed from observed data, seven clinical variables were evaluated as independent predictors of OSA: age, BMI, sex, Epworth Sleepiness Scale score, witnessed apnoeas, dry mouth and arrhythmias. With this new model, the AUC was 0.7991 (95% CI, 0.7668-0.8314) for diagnosing OSA (sensitivity, 75%; specificity, 71%). The results were confirmed using the validation set. A nomogram for predicting OSA was generated based on this new model using statistical software. CONCLUSIONS: BMI can be used as an indicator to screen for OSA in the community. We created an internally validated, highly distinguishable, visual and parsimonious prediction model comprising BMI and other parameters that can be used to identify patients with OSA among outpatients. Use of this prediction model may help to improve clinical decision-making.

Assessment of nonnegative matrix factorization algorithms for electroencephalography spectral analysis.

BACKGROUND: Nonnegative matrix factorization (NMF) has been successfully used for electroencephalography (EEG) spectral analysis. Since NMF was proposed in the 1990s, many adaptive algorithms have been developed. However, the performance of their use in EEG data analysis has not been fully compared. Here, we provide a comparison of four NMF algorithms in terms of accuracy of estimation, stability (repeatability of the results) and time complexity of algorithms with simulated data. In the practical application of NMF algorithms, stability plays an important role, which was an emphasis in the comparison. A Hierarchical clustering algorithm was implemented to evaluate the stability of NMF algorithms. RESULTS: In simulation-based comprehensive analysis of fit, stability, accuracy of estimation and time complexity, hierarchical alternating least squares (HALS) low-rank NMF algorithm (lraNMF_HALS) outperformed the other three NMF algorithms. In the application of lraNMF_HALS for real resting-state EEG data analysis, stable and interpretable features were extracted. CONCLUSION: Based on the results of assessment, our recommendation is to use lraNMF_HALS, providing the most accurate and robust estimation.

Discovery of vanadium complexes bearing tridentate schiff base ligands as novel LSD1 inhibitors.

Lysine specific demethylase (LSD1) plays a pivotal role in epigenetic modulation of gene expression. Abberrant expression of LSD1 was associated with the progress and oncogenesis of multiple human cancers. Herein, we report the preliminary anti-LSD1 evaluation of the synthetic vanadium (V) complexes. Among them, complex 2 showed a moderate inhibitory effect against LSD1 with IC50 value of 19.0 µM, as well as good selectivity over MAO-A/B. Complex 2 is the first vanadium based LSD1 inhibitor, which provides a novel scaffold for the development of LSD1 inhibitor.

[Design, synthesis, antibacterial and anti-cell proliferation activities of [1,2,4]triazino[3,4-h] [1,8]naphthyridine-8-one-7-carboxylic acid derivatives].

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.

[Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, ß-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, ß-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

[Synthesis and antitumor activity of fluoroquinolon-3-yl-s-triazole sulfide ketones and their derivatives from ciprofloxacin].

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.

[Synthesis and anti-proliferative activity of fluoroquinolone C-3 fused heterocyclic α,ß-unsaturated ketones derived from ciprofloxacin].

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, ß-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, ß-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.

[Synthesis, antitumor activity and SAR of C-3 oxadiazole sulfanylacetylhydrazone-substituted fluoroquinolone analogues].

To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.

Comprehensive analysis of the clinical and prognostic significance of SFRP1 and PRKCB expression in non-small cell lung cancer: a retrospective analysis.

OBJECTIVES: Secreted frizzled-related protein 1 (SFRP1) and protein kinase C-B (PRKCB) contribute to cancer progression and angiogenesis. This study intended to detect SFRP1 and PRKCB expression in non-small-cell lung cancer (NSCLC) patients and analyze its association with clinicopathological features. METHODS: A total of 108 NSCLC patients who underwent surgical resection in our hospital between 2012 and 2017 were retrospectively analyzed. SFRP1 and PRKCB expression was detected using immunohistochemical staining. The relationships between SFRP1 and PRKCB expression and clinicopathological data were analyzed using the chi-square method. Kaplan-Meier analysis was used to investigate survival probability over time. The potential risk of NSCLC morbidity associated with SFRP1 and PRKCB levels was analyzed using univariate and multivariate Cox proportional risk models. RESULTS: SFRP1 and PRKCB expression was negative in 114 and 109 of the 180 NSCLC specimens, respectively. SFRP1 expression was significantly associated with TNM stage ( P  < 0.001) and tumor diameter ( P  < 0.001). PRKCB expression was significantly associated with the TNM stage ( P  < 0.001). The correlation between SFRP1 and PRKCB expression was evident ( P  = 0.023). SFRP1(-) or PRKCB(-) patients shows lower survival rates than SFRP1(+) or PRKCB(+) patients ( P < 0.001). SFRP1(-)/PRKCB(-) patients had the worst prognosis ( P < 0.001). Furthermore, the mortality of SFRP1(-) or PRKCB(-) patients was significantly higher than that of SFRP1(+) or PRKCB(+). CONCLUSION: SFRP1 and PRKCB expression can be used to predict prognosis in patients with NSCLC.

Blood urea nitrogen to serum albumin ratio as a new prognostic indicator in type 2 diabetes mellitus patients with chronic kidney disease.

Chronic kidney disease (CKD) is often a common comorbidity in critically ill patients with type 2 diabetes mellitus (T2DM). This study explored the relationship between blood urea nitrogen to serum albumin ratio (BAR) and mortality in T2DM patients with CKD in intensive care unit (ICU). Patients were recruited from the Medical Information Mart database, retrospectively. The primary and secondary outcomes were 90-day mortality, the length of ICU stay, hospital mortality and 30-day mortality, respectively. Cox regression model and Kaplan-Meier survival curve were performed to explore the association between BAR and 90-day mortality. Subgroup analyses were performed to determine the consistency of this association. A total of 1920 patients were enrolled and divided into the three groups (BAR < 9.2, 9.2 ≤ BAR ≤ 21.3 and BAR > 21.3). The length of ICU stay, 30-day mortality, and 90-day mortality in the BAR > 21.3 group were significantly higher than other groups. In Cox regression analysis showed that high BAR level was significantly associated with increased greater risk of 90-day mortality. The adjusted HR (95%CIs) for the model 1, model 2, and model 3 were 1.768 (1.409-2.218), 1.934, (1.489-2.511), and 1.864, (1.399-2.487), respectively. Subgroup analysis also showed the consistency of results. The Kaplan-Meier survival curve analysis revealed similar results as well that BAR > 21.3 had lower 90-day survival rate. High BAR was significantly associated with increased risk of 90-day mortality. BAR could be a simple and useful prognostic tool in T2DM patients with CKD in ICU.

Trimethoxy-benzaldehyde levofloxacin hydrazone inducing the growth arrest and apoptosis of human hepatocarcinoma cells.

BACKGROUND: In order to search for new structural modification strategies on fluoroquinolones, we have designed and synthesized a series of fluoroquinolone derivatives by linking various hydrazine compounds to the C-3 carboxyl group of levofloxacin and assessed their anticancer activities. Several novel levofloxacin derivatives displayed potent cytotoxicity against the tested cancer cell lines in vitro. In the present study, we investigated the effect of 1-Cyclopropyl-6-fluoro-4-oxo-7- piperazin-1, 4-dihydro- quinoline- 3-carboxylic acid benzo [1,3] dioxol-5- ylmethylene- hydrazide (QNT11) on the apoptosis of human hepatocarcinoma cells in vitro. METHODS: The inhibition effects of QNT11 on cell proliferation were examined by MTT assay. Cell apoptosis was determined by TUNEL and DNA agarose gel electrophoresis method. The topoisomerase ΙΙ activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate. Cell cycle progression was analyzed using flow cytometry in conjunction with ethanol fixation and propidium iodide staining. Mitochondrial membrane potential (△ψm) was measured by high content screening image system. The caspase-9, caspase-8, caspase-3, Bcl-2, Bax, CDK1, Cyclin B1and cytochrome c protein expressions were detected by Western blot analysis. RESULTS: QNT11 showed selective cytotoxicity against Hep3B, SMMC-7721, MCF-7 and HCT-8 cell lines with IC50 values of 2.21 µM, 2.38 µM, 3.17 µM and 2.79 µM, respectively. In contrast, QNT11 had weak cytotoxicity against mouse bone marrow mesenchymal stem cells (BMSCs) with IC50 value of 7.46 µM. Treatment of Hep3B cells with different concentrations of QNT11 increased the percentage of the apoptosis cells significantly, and agarose gel electrophoresis revealed the ladder DNA bands typical of apoptotic cells, with a decrease in the mitochondrial membrane potential. Compared to the control group, QNT11 could influence the DNA topoisomerase IIactivity and inhibit the religation of DNA strands, thus keeping the DNA in fragments. There was a significant increase of cytochrome c in the cytosol after 24 h of treatment with QNT11 and a decrease in the mitochondrial compartment. Observed changes in cell cycle distribution by QNT11 treated might be caused by insufficient preparation for G2/M transition. In addition, QNT11 increased the protein expression of Bax, caspase-9, caspase-8, caspase-3, as well as the cleaved activated forms of caspase-9, caspase-8 and caspase-3 significantly, whereas the expression of Bcl-2 decreased. CONCLUSIONS: Our results showed that QNT11 as a fluoroquinolone derivative exerted potent and selectively anticancer activity through the mechanism of eukaryotic topoisomerase II poisoning. The growth inhibition was in large part mediated via apoptosis-associated mitochondrial dysfunction and regulation of Bcl-2 signaling pathways.

Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells.

AIM: To investigate the effects and the molecular mechanisms of fucoxanthin, a major carotenoid found in edible seaweed, on HeLa cells. METHODS: The cytotoxicity of fucoxanthin was evaluated using MTT assay. Cell cycle and apoptosis were evaluated using flow cytometric analysis. Autophagy was detected with acridine orange staining and transient transfection of the GFP-LC3 plasmid into the cells. Protein expression was detected with Western blotting. RESULTS: Treatment of HeLa cells with fucoxanthin (10-80 µmol/L) for 48 h caused dose-dependent cytotoxicity with an IC50 value of 55.1±7.6 µmol/L. Fucoxanthin (10, 20, and 40 µmol/L) dose-dependently induced G0/G1 arrest, but did not change the apoptosis of HeLa cells. The same concentrations of fucoxanthin dose-dependently increased the protein expression of LC3 II (the autophagosome marker) and Beclin 1 (the initiation factor for autophagosome formation) in HeLa cells. Moreover, fucoxanthin dose-dependently decreased the levels of phosphorylated Akt and its downstream proteins p53, p70S6K, and mTOR, and increases the expression of PTEN in HeLa cells. Pretreatment of HeLa cells with 3-methyladenine (5 mmol/L) blocked the cytotoxic effect of fucoxanthin as well as fucoxanthin-induced autophagy. CONCLUSION: Fucoxanthin exerts autophagy-dependent cytotoxic effect in HeLa cells via inhibition of Akt/mTOR signaling pathway.

[Synergistic antitumor effects of tanshinone II A in combination with cisplatin via apoptosis in the prostate cancer cells].

Treatment with the combination of Chinese herbs and cytotoxic chemotherapies showed a higher survival rate in clinical trials. In this report, the results demonstrated that the tanshinone II A, a key component of Salvia miltiorrhiza bunge, when it is combined with the cytotoxic drug cisplatin showed synergistic antitumor effects on human prostate cancer PC3 cells and LNCaP cells in vitro. Antiproliferative effects were detected with MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. Protein expression was detected by Western blotting. The intracellular concentration of cisplatin was detected by high performance liquid chromatography. The results demonstrated that tanshinone II A significantly enhanced the antiproliferative effects of cisplatin on human prostate cancer PC3 cells and LNCaP cells with the increase of the intracellular concentration of cisplatin. These effects were correlated with cell cycle arrested at S phase and cell apoptosis. The apoptosis might be achieved through death receptor pathway and mitochondrial pathway. Furthermore, the Bcl-2 family members were also involved in this apoptotic process. Collectively, these results indicated that the combination of tanshinone II A and cisplatin had a better treatment effect in vitro not only on androgen-dependent LNCaP cells but also on androgen-independent PC3 cells.

[Molecular mechanism of ophiopogonin B induced cellular autophagy of human cervical cancer HeLa cells].

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.

Formation Tracking of Multiagent Systems With Time-Varying Actuator Faults and Its Application to Task-Space Cooperative Tracking of Manipulators.

This article is concerned with a fault-tolerant formation tracking problem of nonlinear systems under unknown faults, where the leader's states are only accessible to a small set of followers via a directed graph. Under these faults, not only the amplitudes but also the signs of control coefficients become time-varying and unknown. The current setting will enhance the investigated problem's practical relevance and at the same time, it poses nontrivial design challenges of distributed control algorithms and convergence analysis. To solve this problem, a novel distributed control algorithm is developed by incorporating an estimation-based control framework together with a Nussbaum gain approach to guarantee an asymptotic cooperative formation tracking of nonlinear networked systems under unknown and dynamic actuator faults. Moreover, the proposed control framework is extended to ensure an asymptotic task-space coordination of multiple manipulators under unknown actuator faults, kinematics, and dynamics. Lastly, numerical simulation results are provided to validate the effectiveness of the proposed distributed designs.