Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous non-Hodgkin lymphoma that is extremely aggressive and has an intermediate to high malignancy. Some patients still experience treatment failure, relapse, or resistance to rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) therapy. Therefore, there is an urgent need for further research on new agents for the treatment of DLBCL. AP-48 is an aaptamine alkaloid analog with potent anti-tumor effects that originates from marine natural products. In this study, we found that AP-48 exhibits dose-dependent cytotoxicity in DLBCL cell lines. Flow cytometry showed that AP-48 induced cell cycle arrest in the G0/G1 phase in SU-DHL-4 and Farage cells and in the S phase in WSU-DLCL-2 cells. AP-48 also accelerated apoptosis via the caspase-3-mediated intrinsic apoptotic pathway. Further experiments demonstrated that AP-48 exerted its anti-DLBCL effects through the PI3K/AKT/mTOR pathway, and that the PI3K agonist YS49 partially alleviated the inhibition of cell proliferation and apoptosis induced by AP-48. Finally, in a tumor xenograft model, AP-48 inhibited tumor growth and promoted apoptosis in tumor tissues, indicating its therapeutic potential in DLBCL.

Predictive modeling of microbial single cells: A review.

In practice, food products tend to be contaminated with food-borne pathogens at a low inoculum level. However, the huge potential risk cannot be ignored because microbes may initiate high-speed growth suitable conditions during the food chain, such as transportation or storage. Thus, it is important to perform predictive modeling of microbial single cells. Several key aspects of microbial single-cell modeling are covered in this review. First, based on previous studies, the techniques of microbial single-cell data acquisition and growth data collection are presented in detail. In addition, the sources of microbial single-cell variability are also summarized. Due to model microbial growth, traditional deterministic mathematical models have been developed. However, most models fail to make accurate predictions at low cell numbers or at the single-cell level due to high cell-to-cell heterogeneity. Stochastic models have been a subject of great interest; and these models take into consideration the variability in microbial single-cell behavior.

Modeling the Effect of Water Activity, pH, and Temperature on the Probability of Enterotoxin A Production by Staphylococcus aureus.

The objectives of this study were to develop a probability model of Staphylococcus aureus enterotoxin A (SEA) production as affected by water activity (a(w)), pH, and temperature in broth and assess its applicability for milk. The probability of SEA production was assessed in tryptic soy broth using 24 combinations of a(w) (0.86 to 0.99), pH (5.0 to 7.0), and storage temperature (10 to 30°C). The observed probabilities were fitted with a logistic regression to develop a probability model. The model had a concordant value of 97.5% and concordant index of 0.98, indicating that the model satisfactorily describes the probability of SEA production. The model showed that a(w), pH, and temperature were significant factors affecting the probability of toxin production. The model predictions were in good agreement with the observed values obtained from milk. The model may help manufacturers in selecting product pH and a(w) and storage temperatures to prevent SEA production.

[Comparison of Predicting Blueberry Firmness and Elastic Modulus with Hyperspectral Reflectance, Transmittance and Interactance Imaging Modes].

In this study, a imaging system with hyperspectral reflectance, transmittance and interactance was constructed for estimate the firmness and elastic modulus of blueberry. The comparisons of these three imaging modes were carried out. This hyperspectral system could also be applied for scattering modewhile this mode was not suitable for small fruit such as blueberry. The reflectance hypercubes were segmented with the algorithm based on the Otsu method, and the transmittance and interactance hypercubes were processed with the algorithms based on region growing approach. Subsequently, the extracted spectra were pretreated with the Standard Normal Variate (SNV) and Savitzky-Golay of the first derivative (Der), and least squares-support vector machine was applied for the establishment of the corresponding prediction models. The obtained results demonstrated that -reflectance-SNV model could predict blueberry firmness with correlation coefficient of prediction sample set (Rp) of 0.80 and the ratio of percent deviation (RPD) of 1.76 among the models using full spectra. The elastic modulus of blueberry was better estimated by the full transmittance spectra subjected to SNV pretreatment with Rp (RPD) of 0.78 (1.74) than the other models. Furthermore, Random Frog selection approach could to some extent reduce the uninformative wavelengths while increasing the prediction accuracy of the established models. Random Frog-Interactance-Der model achieved Rp (RPD) of 0.80 (1.83) for blueberry firmness, but the number of wavelength was 140. In the case of blueberry elastic modulus, random frog-transmittance-SNV showed the relatively superior performance compared to the other models, with Rp (RPD) of 0.82 (1.83) and fewer wavelength number of 20.

Modelling postharvest quality of blueberry affected by biological variability using image and spectral data.

BACKGROUND: Hyperspectral reflectance and transmittance sensing as well as near-infrared (NIR) spectroscopy were investigated as non-destructive tools for estimating blueberry firmness, elastic modulus and soluble solid content (SSC). Least squares-support vector machine models were established from these three spectra based on samples from three cultivars viz. Bluecrop, Duke and M2 and two harvest years viz. 2014 and 2015 for predicting blueberry postharvest quality. RESULTS: One-cultivar reflectance models (establishing model using one cultivar) derived better results than the corresponding transmittance and NIR models for predicting blueberry firmness with few cultivar effects. Two-cultivar NIR models (establishing model using two cultivars) proved to be suitable for estimating blueberry SSC with correlations over 0.83. Rp (RMSEp ) values of the three-cultivar reflectance models (establishing model using 75% of three cultivars) were 0.73 (0.094) and 0.73 (0.186), respectively , for predicting blueberry firmness and elastic modulus. For SSC prediction, the three-cultivar NIR model was found to achieve an Rp (RMSEp ) value of 0.85 (0.090). Adding Bluecrop samples harvested in 2014 could enhance the three-cultivar model robustness for firmness and elastic modulus. CONCLUSION: The above results indicated the potential for using spatial and spectral techniques to develop robust models for predicting blueberry postharvest quality containing biological variability. © 2015 Society of Chemical Industry.

Perpetual impact of pregnancy-induced hypertension on blood pressure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the perpetual impact of pregnancy-induced hypertension on blood pressure.</p><p><b>METHODS</b>This retrospective cohort study included 782 cases of pregnant women who hospitalized at Kailuan Linxi hospital between October 1976 and August 2001. Patients were divided to with pregnancy induced hypertension (PIH, n = 77) group and non pregnancy induced hypertension (NPIH, n = 705) group. Patients were followed for 5 to 34 years (mean 18.8 +/- 5.3 years), the incidence of essential hypertension was obtained in July 2006-September 2007.</p><p><b>RESULTS</b>(1) The cumulative incidence of essential hypertension during follow up was significantly high in PIH group (29.87%) than that in NPIH group 18.87% (P = 0.022). (2) At the final follow up, waist circumference; [(86.06 +/- 10.15) cm vs. (83.07 +/- 8.19) cm, P = 0.015], BMI [(24.83 +/- 4.01) kg/m(2) vs. (23.50 +/- 3.39) kg/m(2), P = 0.006], TC [(5.11 +/- 0.88) mmol/L vs. (4.89 +/- 0.94) mmol/L, P = 0.045] and GLU [(5.57 +/- 1.78) mmol/L vs. (5.20 +/- 1.38) mmol/L, P = 0.010] were all significantly higher in PIH group than those in NPIH group. (3) After adjustment of age and BMI, PIH was still significantly correlated with long-term systolic blood pressure levels (P = 0.048), fasting glucose level was also significantly associated with long-term systolic blood pressure. Age, BMI, white blood cell count and uric acid were also predictors for perpetual systolic and diastolic blood pressure levels.</p><p><b>CONCLUSIONS</b>Incidence of essential hypertension in women with PIH was higher than that in women without PIH. After adjustment of covariates including age, BMI, and glucose, PIH was significantly associated with the level of systolic blood pressure. BMI, fasting glucose and cholesterol levels might contribute to the increase of systolic blood pressure in patients with PIH.</p>

Association of vascular endothelial growth factor 936C/T polymorphism and the susceptibility to colorectal adenoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To examine the association between polymorphism of vascular endothelial growth factor(VEGF)1498 C/T,936 C/T and colorectal adenoma genetic susceptibility.</p><p><b>METHODS</b>A case-control study of 224 colorectal adenomas and 200 controls was conducted and VEGF genotypes were determined based on TaqMan-probe assay. The epidemiological factors were collected through questionnaire. Accordingly, the clinicopathological data of each sample were also investigated.</p><p><b>RESULTS</b>The carriage of 936 CT and CT+TT genotypes had significantly higher risk of colorectal adenoma (CT vs. CC, OR=2.00, 95% CI: 1.23-3.25, P=0.006; CT+TT vs. CC, OR=2.04, 95% CI:1.28-3.26, P=0.003). 936-T allele carriage had increased risk of colorectal adenoma (OR=1.91, 95% CI:1.25-2.91, P=0.003). The genotypes of 1498 C/T and the frequency of C/T allele showed no differences between healthy persons and patients (P>0.05). In patients with 936 CT+TT and 936-T allele implied a tendency of villous adenoma category (CT+TT vs. CC, OR=2.54, 95% CI:1.12-5.75, P=0.040; T allele vs. C allele, OR=3.08, 95% CI, 1.64-5.80, P=0.001).</p><p><b>CONCLUSION</b>VEGF 936 C/T polymorphism can influence susceptibility to colorectal adenoma.</p>

Expeditious total syntheses of camptothecin and 10-hydroxycamptothecin.

New expeditious total syntheses of (S)-camptothecin (16% overall yield, 95% ee) and (S)-10-hydroxycamptothecin (14% overall yield, 99% ee) have been accomplished, respectively, starting from readily available and inexpensive materials. Development, optimization, and successful application of the cascade reaction consisting of a pyrrolidine-catalyzed Michael addition, an intramolecular aldol condensation, and an oxidative aromatization, the intramolecular oxa Diels-Alder cycloaddition, and the Sharpless asymmetric dihydroxylation make these two new syntheses more efficient and straightforward.

Effects of Long-term Treatment with Hydrochlorothiazide Combined Spironolactone or Captopril on Left Ventricular Hypertrophy in Hypertensive Patients / 中华高血压杂志

0.05);2)After 12,24,36 months' treatment,BP was decreased significantly in each group (P0.05).Conclusion Both combined spirono- lactone/HCTZ and captopril/HCTZ significantly reduced BP and LVMI or LVMI and the maguitude of reduction was further enhanced after prolonged treatment.

Association of polymorphism in alpha-adducin gene with antihypertensive effect of Hydrochlorothiazide / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the association between G614T single nuclear polymorphism (SNP) of the alpha-adducin gene and the antihypertensive effect of hydrochlorothiazide (HCTZ) in essential hypertensive (EH) patients.</p><p><b>METHODS</b>Eight hundred twenty nine EH patients were given 12.5 mg HCTZ/d for six weeks. Alpha-adducin gene G614T SNP in the tenth exon was determined by PCR-RFLP in 754 patients with complete records. All the patients were grouped according to TT, GT and GG genotypes.</p><p><b>RESULTS</b>After 6 weeks of HCTZ treatment, the decreases in DBP and MAP of patients carrying 614T allele of alpha-adducin were significantly greater than that of those carrying GG homozygotes (P < 0.05). The decreases in SBP and MAP were significantly greater in patients with the TT genotype as compared with GT or GG genotype (P < 0.05). The effective rate of BP fall by HCTZ was higher in patients with TT genotype than those with GT or GG genotype (P < 0.05). Multivariate stepwise regression analysis showed that the TT genotype and the baseline SBP were the two major predictors affecting the decrease in SBP.</p><p><b>CONCLUSION</b>The present study suggests that the alpha-adducin G614T polymorphism is associated with the antihypertensive effect of HCTZ, which is more effective in patients with TT genotype.</p>