1-(3-Pyrid­yl)pyrrolidine-2,5-dione

In the title mol­ecule, C9H8N2O2, the dihedral angle between the pyridine and the pyrrolidine rings is 64.58 (12)°. In the crystal structure, weak C—H⋯π-electron ring inter­actions stabilize the packing

Stochastic bifurcation characteristics of cantilevered piezoelectric energy harvester

Stochastic bifurcation characteristics of cantilevered piezoelectric energy harvester were studied in this paper. Von de Pol differencial item was introduced to interpret the hysteretic phenomena of piezoelectric ceramics, and then the nonlinear dynamic model of piezoelectric cantilever beam subjected to axial stochastic excitation was developed. The stochastic stability of the system was analyzed, and the steady-state probability density function and the joint probability density function of the dynamic response of the system were obtained, and then the conditions of stochastic Hopf bifurcation were analyzed. Numerical simulation shows that stochastic Hopf bifurcation appears when bifurcation parameter varies, which can increase vibration amplitude of cantilever beam system and improve the efficiency of piezoelectric energy harvester. Finally, the theoretical and numerical results were proved by experiments. The results of this paper are helpful to application of cantilevered piezoelectric energy harvester in engineering fields

Epidemic Pleurodynia Caused by Coxsackievirus B3 at a Medical Center in Northern Taiwan

Epidemic pleurodynia is seldom reported in Southeast Asia and there has been no report from Taiwan. We conducted a retrospective chart review of children = 18 years of age in the National Taiwan University Hospital from January 1 to December 31, 2005. Epidemic pleurodynia was defined as an acute illness characterized by sharp localized pain over the chest or upper abdomen. Patients with known heart diseases or pulmonary consolidations were excluded. In total, 28 patients met the case definition of epidemic pleurodynia. Coxsackievirus B3 (CB3) was isolated in 15 (60%) of the 25 throat swab specimens. Four (14%) of the 28 patients presented chest wall tenderness and only one (6%) of the 18 patients tested had an elevated creatinine kinase level. Twenty-one (75%) of the 28 patients described pleuritic chest pains and 10 (45%) of the 22 chest radiographies exhibited pulmonary infiltrates or pleural effusions. Six patients were observed with tonsillar exudates and one was confirmed to have a CB3 urinary tract infection. The clinical features and radiological findings suggest that CB3-associated epidemic pleurodynia might be a disease of the pleura and occasionally spreads to nearby tissues, resulting in chest wall myositis, pulmonary infiltrates and myopericarditis

Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation

Levothyroxine, a synthetic form of thyroid hormone, has been clinically used to treat thyroid hormone deficiency. UDP-glucuronosyltransferases (UGTs) are important phase II drug-metabolizing enzymes, and UGTs-inhibition based drug-drug interaction has been widely reported. The aim of the present study is to investigate the inhibitory effect of levothyroxine towards UGT1A6-catalyzed 4-methylumbelliferone (4-MU) glucuronidation. The results showed that levothyroxine inhibited UGT1A6-catalyzed 4-MU glucuronidation reaction in a dose-dependent manner. Furthermore, Lineweaver-Burk and Dixon plots showed the inhibition of UGT1A6 by levothyroxine was best fit to competitive inhibition, and the inhibition kinetic parameter (Ki ) was determined to be 15.3 μM. Given that UGT1A6 is one of the most important UGT isoforms catalyzing the glucuronidation reaction of many important clinical drugs, including aspirin and serotonin, inhibition of UGT1A6 activity by levothyroxine will significantly influence the pharmacokinetic behaviour of these drugs. Therefore, clinical drug-drug interaction due to the inhibition of UGT1A6 by levothyroxine should paid much attention.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Molecular Epidemiology of SARS-associated Coronavirus, Beijing

Viral adaptation to the host may be occurring under selective immune pressure

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse

Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear.Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables.Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41–0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26–0.68); hospital mortality HR 0.70, 95% CI 0.50–0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34–0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26–0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50–0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16–0.69).Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings

Steroid-associated hip joint collapse in bipedal emus

In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients

Identification of a Novel Bcl-2 Inhibitor by Ligand-Based Screening and Investigation of Its Anti-cancer Effect on Human Breast Cancer Cells

Bcl-2 family protein is an important factor in regulating apoptosis and is associated with cancer. The anti-apoptotic proteins of Bcl-2 family, such as Bcl-2, are overexpression in numerous tumors, and contribute to cancer formation, development, and therapy resistance. Therefore, Bcl-2 is a promising target for drug development, and several Bcl-2 inhibitors are currently undergoing clinical trials. In this study, we carried out a QSAR-based virtual screening approach to develop potential Bcl-2 inhibitors from the SPECS database. Surface plasmon resonance (SPR) binding assay was performed to examine the interaction between Bcl-2 protein and the screened inhibitors. After that, we measured the anti-tumor activities of the 8 candidate compounds, and found that compound M1 has significant cytotoxic effect on breast cancer cells. We further proved that compound M1 downregulated Bcl-2 expression and activated apoptosis by inducing mitochondrial dysfunction. In conclusion, we identified a novel Bcl-2 inhibitor by QSAR screening, which exerted significant cytotoxic activity in breast cancer cells through inducing mitochondria-mediated apoptosis

Antimetastatic Effects of Norcantharidin on Hepatocellular Carcinoma by Transcriptional Inhibition of MMP-9 through Modulation of NF-kB Activity

The rate of morbidity and mortality of hepatocellular carcinoma (HCC) in Taiwan has not lessened because of difficulty in treating tumor metastasis. Norcantharidin (NCTD) is currently used as an anticancer drug for hepatoma, breast cancer, and colorectal adenocarcinoma. NCTD possesses various biological anticancer activities, including apoptosis. However, detailed effects and molecular mechanisms of NCTD on metastasis are unclear. Thus, HCC cells were subjected to treatment with NCTD and then analyzed to determine the effects of NCTD on cell metastasis.Modified Boyden chamber assays revealed that NCTD treatment inhibited cell migration and invasion capacities of HCC cells substantially. Results of zymography and western blotting showed that activities and protein levels of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (u-PA) were inhibited by NCTD. Western blot analysis showed that NCTD inhibits phosphorylation of ERK1/2. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of NCTD on MMP-9 and u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay for analyzing the genomic DNA sequences bound to these proteins was reactive to the transcription protein nuclear factor (NF)-kappaB, which was inhibited by NCTD. The expression of NF-kappa B was measured by western blot analysis, which revealed decreased nuclear-factor DNA-binding activity after NCTD treatment.NCTD inhibited MMP-9 and u-PA expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway which serves as a powerful chemopreventive agent in HCC cell metastasis