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This study is aimed to assess the biodegradation of sulfadiazine (SDZ) and characterization of heavy metal resistance in three pure bacterial cultures and also their chemotactic response towards 2-aminopyrimidine. The bacterial cultures were isolated from pig manure, activated sludge and sediment samples, by enrichment technique on SDZ (6 mg L-1). Based on the 16S rRNA gene sequence analysis, the microorganisms were identified within the genera of Paracoccus, Methylobacterium and Kribbella, which were further designated as SDZ-PM2-BSH30, SDZ-W2-SJ40 and SDZ-3S-SCL47. The three identified pure bacterial strains degraded up to 50.0, 55.2 and 60.0% of SDZ (5 mg L-1), respectively within 290 h. On the basis of quadrupole time-of-flight mass spectrometry and high performance liquid chromatography, 2-aminopyrimidine and 4-hydroxy-2-aminopyrimidine were identified as the main intermediates of SDZ biodegradation. These bacteria were also able to degrade the metabolite, 2-aminopyrimidine, of the SDZ. Furthermore, SDZ-PM2-BSH30, SDZ-W2-SJ40 and SDZ-3S-SCL47 also showed resistance to various heavy metals like copper, cadmium, chromium, cobalt, lead, nickel and zinc. Additionally, all three bacteria exhibited positive chemotaxis towards 2-aminopyrimidine based on the drop plate method and capillary assay. The results of this study advanced our understanding about the microbial degradation of SDZ, which would be useful towards the future SDZ removal in the environment. [ABSTRACT FROM AUTHOR]

Aim: To investigate the inhibitory effect of pseudolaric acid B on subcutaneous xenografts of human gastric adenocarcinoma and the underlying molecular mechanisms involved in its multidrug resistance. Methods: Human gastric adenocarcinoma SGC7901 cells and drug-resistant SGC7901/ADR cells were injected into nude mice to establish a subcutaneous xenograft model. The effects of pseudolaric acid B with or without adriamycin treatment were compared by determining the tumor size and weight. Cyclo-oxygenase-2, protein kinaseC-α and P-glycoprotein expression levels were determined by immunohistochemistry and western blot. Results: Pseudolaric acid B significantly suppressed the tumor growth induced by SGC7901 cells and SGC7901/ADR cells. The combination of pseudolaric acid B and the traditional chemotherapy drug adriamycin exhibited more potent inhibitory effects on the growth of gastric cancer in vivo than treatment with either pseudolaric acid B or adriamycin alone. Protein expression levels of cyclo-oxygenase-2, protein kinaseC-α and P-glycoprotein were inhibited by pseudolaric acid B alone or in combination with adriamycin in SGC7901/ADR cell xenografts. Conclusion: Pseudolaric acid B has a significant inhibitory effect and an additive inhibitory effect in combination with adriamycin on the growth of gastric cancer in vivo, which reverses the multidrug resistance of gastric neoplasm to chemotherapy drugs by downregulating the Cox-2/PKC-α/P-gp/mdr1 signaling pathway. [ABSTRACT FROM AUTHOR]

As a core subunit of the SCF complex that promotes protein degradation through the 26S proteasome, S-phase kinase-associated protein 1 (SKP1) plays important roles in multiple cellular processes in eukaryotes, including gibberellin (GA), jasmonate, ethylene, auxin and light responses. P7-2 encoded by Rice black streaked dwarf virus (RBSDV), a devastating viral pathogen that causes severe symptoms in infected plants, interacts with SKP1 from different plants. However, whether RBSDV P7-2 forms a SCF complex and targets host proteins is poorly understood. In this study, we conducted yeast two-hybrid assays to further explore the interactions between P7-2 and 25 type I Oryza sativa SKP1-like (OSK) proteins, and found that P7-2 interacted with eight OSK members with different binding affinity. Co-immunoprecipitation assay further confirmed the interaction of P7-2 with OSK1, OSK5 and OSK20. It was also shown that P7-2, together with OSK1 and O. sativa Cullin-1, was able to form the SCF complex. Moreover, yeast two-hybrid assays revealed that P7-2 interacted with gibberellin insensitive dwarf2 (GID2) from rice and maize plants, which is essential for regulating the GA signaling pathway. It was further demonstrated that the N-terminal region of P7-2 was necessary for the interaction with GID2. Overall, these results indicated that P7-2 functioned as a component of the SCF complex in rice, and interaction of P7-2 with GID2 implied possible roles of the GA signaling pathway during RBSDV infection. [ABSTRACT FROM AUTHOR]

NFATs are transcription factors involved in immune activation and tumor progression. Previous reports showed that DYRK1A suppressed NFATc2 transcriptional activity through phosphorylation. Nonetheless, our results showed that DYRK1A increased NFATc1/αA protein level and subsequent transcriptional activity. DYRK1A phosphorylation of NFATc1/αA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation. Our results imply that DYRK1A is a positive kinase in regulation of NFATc1. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) is an arising public health problem in Asia, including China. Epidemiological data is necessary to enable judicious public health responses and interventions. We analyzed the epidemiological and laboratory data of 759,301 HFMD cases reported to the Hunan Provincial Center for Disease Control and Prevention from 1 January 2009 to 31 December 2014. Univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatality in HFMD. The incidence of HFMD was highest among children aged 1–3 years, compared with other age groups. Of the total HFMD cases, 7,222 (0.95%) were considered severe and 338 (0.04%) were fatal. Enterovirus-A71 was the major cause of severe and fatal cases (65.75% and 88.78%, respectively). For severe cases, the median time from symptom onset to diagnosis was 0.5 days (interquartile range [IQR] 0–1.5 days); the median time from diagnosis to severe illness was 2 days (IQR 1–3 days). For fatal cases, the median time from symptom onset to diagnosis was 0.5 days (IQR 0–1.5 days); the median time from diagnosis to death was 1.5 days (IQR 0.5–2.5 days). In multivariable analysis, the abuse of antibiotic, glucocorticoid and pyrazolone in village clinics at basic medical institutions were identified as independent risk factors for HFMD fatal cases. In conclusion, our results suggest that the future direction to control and respond to HFMD is intensive surveillance of enterovirus-A71 and improving the ability to diagnose disease and treat patients, especially in basic medical institutions. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to assess atrial fibrillation (AF) and vulnerability in Wolff-Parkinson-White (WPW) syndrome patients using two-dimensional speckle tracking echocardiography (2D-STE). Methods: All patients were examined via transthoracic echocardiography and 2D-STE in order to assess atrial function 7 days before and 10 days after RF catheter ablation. A postoperative 3-month follow-up was performed via outpatient visit or telephone calls. Results: Results showed significant differences in both body mass index (BMI) and supraventricular tachycardia (SVT) duration between WPW patients and DAVNP patients (both P<0.05). Echocardiography revealed that the maximum left atrial volume (LAVmax) and the left ventricular mass index (LVMI) in diastole increased noticeably in patients with WPW compared to patients with DAVNP both before and after ablation (all P<0.05). Before ablation, there were obvious differences in the levels of SRs, SRe, and SRa from the 4-chamber view (LA) in the WPW patients group compared with patients in the DAVNP group (all P<0.05). In the AF group, there were significant differences in the levels of systolic strain rate (SRs), early diastolic strain rate (SRe), and late diastolic strain rate (SRa) from the 4-chamber view (LA) both before and after ablation (all P<0.05). In the non-AF group, there were decreased SRe levels from the 4-chamber view (LA/RA) pre-ablation compared to post-ablation (all P<0.05). Conclusion: Our findings provide convincing evidence that WPW syndrome may result in increased atrial vulnerability and contribute to the development of AF. Further, RF catheter ablation of AAV pathway can potentially improve atrial function in WPW syndrome patients. Two-dimensional speckle tracking echocardiography imaging in WPW patients would be necessary in the evaluation and improvement of the overall function of RF catheter ablation in a long-term follow-up period. [ABSTRACT FROM AUTHOR]