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Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are currently the mainstay treatment for preventing thrombosis-induced ischemic stroke in patients with atrial fibrillation (AF), deep vein thrombosis (DVT), or previous infarction. However, such management may potentially induce antithrombotic-associated intracranial hemorrhage, leading to significantly adverse clinical outcomes. To investigate the risk of spontaneous intracranial hemorrhage (sICH) in patients under therapeutic anticoagulation., Methods: This retrospective cohort study used a database established by Kaohsiung Veterans General Hospital to estimate the risk of first onset sICH in patients with AF, DVT or previous stroke who were 18 years old or older, and who had been on at least three months continuous long-term treatment with the oral anticoagulants aspirin, warfarin, or NOACs. In addition, we used propensity-score matching to minimize bias and Cox proportional hazards ratio to compare the risk of sICH among patients prescribed these anticoagulants., Results: We analyzed the data of 546 patients (182 aspirin users, 182 warfarin users, and 182 NOAC users). 180 (20 taking aspirin, 74 warfarin, and 86 NOACs) developed new onset sICH before seven years. No new onset cases were found after 7 years. Importantly, those taking NOACs were found to be at a higher risk of early onset hemorrhage (47.80 %) compared to the groups taking aspirin (11.10 %) and warfarin (47.80 %) with a median time-to-occurrence being 2.50, 4.00, and 4.40 years, respectively., Conclusions: Though NOACs prevented ischemic stroke, they were used with a higher risk of early onset spontaneous ICH at our large medical center., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024. Published by Elsevier B.V.)

Background: Some infants with urinary tract infection (UTI) may exhibit concurrent bacteremia, potentially leading to septic shock or bacterial meningitis. Identifying risk factors for bacteremia in infants with UTI is crucial for prompt intervention to prevent subsequent adverse outcomes., Methods: Between 2015 and 2021, a total of 632 infants with UTI aged ≤12 months were enrolled at Kaohsiung Veterans General Hospital (KSVGH), among whom 20 had concurrent bacteremia. We analyzed their differences in outcomes and demographic, clinical, and laboratory characteristics. Independent risk factors for bacteremic UTI were identified using binary logistic regression analysis., Results: A positive underlying disease (including congenital anomalies of kidney and urinary tract [CAKUT] and prematurity), C-reactive protein (CRP) > 8 mg/dL, lower body weight, and positive urinary nitrite were independent risk factors for infants with UTI and bacteremia., Conclusions: Physicians should be mindful of the potential for bacteremia to develop in infants with UTI, particularly those with concurrent positive underlying diseases or CRP >8 mg/dL., Competing Interests: Declaration of competing interest No potential conflicts of interest are declared by the authors., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Cryptococcal meningitis (CM) is a severe central nervous system infection. In patients with HIV infections and coexisting CM, elevated baseline cerebrospinal fluid (CSF) lactate levels can predict increased mortality. However, the CSF lactate level's significance in patients with CM who are HIV negative remains unclear, necessitating further investigation to elucidate the potential distinctions and enhance patient management. This study investigated the significance of CSF lactate levels in patients with CM who were HIV negative., Methods: This retrospective study utilized data from the clinical databases of patients who underwent lumbar punctures at a medical center in Kaohsiung City, southern Taiwan. Demographic data, CSF lactate levels, routine CSF analyses, and hematologic and neurologic findings were evaluated. The optimal CSF lactate threshold value was determined by the Youden index., Results: This retrospective study included 70 patients with CM, among whom 44 (63%) and 26 (37%) tested negative and positive for HIV, respectively. The group without HIV exhibited higher CSF lactate levels, with an optimal CSF lactate cutoff point of 7.935 mmol/L for predicting 90-day mortality, resulting in significant predictive accuracies (area under the curve, 0.755; sensitivity, 57.1%; specificity, 100%); this value was an independent mortality predictor in patients who were HIV negative. In patients with CM who were HIV negative, CSF lactate levels ≥7.935 mmol/L correlated with higher mortality rates but without statistical significance. All patients with CM who were HIV negative and had CSF lactate levels ≥7.935 mmol/L died within 3 months of admission., Conclusions: Patients with CM who were HIV negative had elevated CSF lactate levels that correlated with adverse outcomes, enabling early identification of high-risk individuals., Competing Interests: Potential conflicts of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: A significant rise in the use of assisted reproductive technology (ART) has been observed, but concerns about its impact on neonatal outcomes have been considered. The aim of this retrospective cohort study is to determine the association between ART and the risk of neonatal complications and congenital anomalies within a recent time period., Methods: This retrospective study enrolled infants born after 20 weeks of gestation at a tertiary hospital in Taiwan between January 2019 and December 2021. The study population was divided into two groups: (1) ART pregnancy group and (2) natural pregnancy group. Maternal and neonatal characteristics, pregnancy complications, and neonatal outcomes were compared between the two groups. Multivariate logistic regression was used to adjust for maternal characteristics, preexisting maternal conditions, pregnancy complications, delivery methods, and infant characteristics., Results: This study enrolled 1770 infants comprising 289 in the ART pregnancy group and 1481 in the natural pregnancy group. The ART pregnancy group showed higher rates of multiple births, preterm births, low birth weights, and longer hospitalization periods. In the stratified analyses that were conducted on singleton births, no significant difference was observed. In the case of multiple births, lower rates of preterm birth, low birth weight, and respiratory support were observed in the ART pregnancy group. After adjusting for maternal and infant characteristics, ART was not considered a significant risk factor for adverse neonatal outcomes, including mortality, complications, and congenital anomalies., Conclusion: Although ART pregnancies were more likely to result in multiple births and furthermore adverse outcomes, ART itself was not associated with an increased risk of poor neonatal outcomes. By implementing measures to control the number of implanted embryos, ensuring appropriate prenatal screening, and providing comprehensive postnatal care, the risks associated with increased multiple pregnancies caused by ART may be reduced., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Urine leukocyte count under microscopy is one of the most frequently used routine screening tests for urinary tract infection (UTI). Nevertheless, it is observed that pyuria is lacking in 10-25% of children with UTI. This study aims to determine the factors related to pyuria-negative UTI in young infants aged under four months old., Method: This retrospective cross-sectional study was conducted on 157 patients aged under 4 months old with UTI. All subjects had paired urinalysis and urine culture, which were collected via transurethral catheterization. According to the results of their urinalysis, the patients were then classified as UTI cases with pyuria and UTI cases without pyuria. The clinical characteristics and outcomes of both groups were analyzed., Result: Among the 157 UTI patients, the prevalence of pyuria-negative UTI was 44%. Significant risk factors associated with pyuria-negative UTI included non-E.coli pathogens, younger age, shorter duration of fever prior to hospital visit, lower white blood cell (WBC) count upon hospital visit, and absence of microscopic hematuria., Conclusions: We found that non-E.coli uropathogens were the strongest factor related to pyuria-negative UTI. The absence of pyuria cannot exclude the diagnosis of UTI in young infants, and it's reasonable to perform both urinalysis and urine culture as a part of the assessment of febrile or ill-looking young infants., Competing Interests: Declaration of competing interest The authors declare that they have no potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Urinary tract infection (UTI) is a potential cause of neonatal jaundice. Nevertheless, there remains a lack of consensus regarding appropriate screening practices for UTI in infants with hyperbilirubinemia. This study aimed to analyze a group of jaundiced infants to assess the prevalence of UTI, explore potential risk factors, and examine the impact of UTI on the course and severity of neonatal jaundice., Methods: This retrospective case-control study was conducted on 150 jaundiced infants (aged < 8 weeks) without a known etiology in the hyperbilirubinemia work-up. All subjects underwent phototherapy treatment and UTI screening by catheterization. They were then classified into UTI and non-UTI groups based on urine culture results, with a positive urine culture indicating the growth of ≥10,000 colony-forming units. The clinical characteristics and jaundice-related parameters of both groups were analyzed., Results: Among the 150 jaundiced patients, the prevalence of UTI was 29%. There was a significantly higher male predominance in the UTI group, and patients with UTI also had a significantly longer duration of hospitalization compared to those without UTI. Significant risk factors associated with UTI in jaundiced infants included male gender and a peak total bilirubin level higher than 18 mg/dl during hospitalization. The most common pathogens identified in urine culture were Escherichia coli (41.9%) and Enterococcus faecalis (30.2%)., Conclusion: In cases of neonatal jaundice where the underlying cause is not evident, screening for UTI should be performed, particularly when associated risk factors or inadequate response to phototherapy is present., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chen, Hsu, Yao, Chang, Wang and Fang.)

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r&gt;0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.

An efficient visible-light-induced Staudinger [2 + 2] annulation reaction between α-diazo ketones and dibenzo[ b , f ][1,4]oxazepine/thiazepine-imines under catalyst-free conditions has been developed. This protocol provides a facile method to synthesize tetracyclic dibenzo[ b , f ][1,4]oxazepine/thiazepine-fused β-lactams bearing a quaternary carbon center with a broad substrate scope and high efficiency (37 examples, up to >99% yield).

Herein, an NHC ( N -heterocyclic carbene)-catalyzed radical coupling reaction between aldehydes and azobis(isobutyronitrile) (AIBN) has been developed. This method provides an efficient and convenient approach for the synthesis of β-ketonitriles containing a quaternary carbon center (31 examples, up to >99% yield) utilizing commercially available substrates. This protocol features broad substrate scope, good functional group tolerance, and high efficiency under metal-free and mild reaction conditions.

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C&#95;(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Herein, a copper catalyzed asymmetric propargylation of 2-oxindole-3-carboxylate esters with terminal propargylic esters is described. This strategy successfully provides a direct approach to constructing a broad range of chiral C3-tetrasubstituted oxindoles with contiguous tertiary and quaternary carbon stereocenters in high yields and excellent enantioselectivities (16 examples, up to 99% yield and 98% ee). Moreover, the diastereoisomers of the two newly formed stereocenters can be separated by silica gel chromatography, thereby providing a valuable stereoselective access to all four possible stereoisomers of C3-tetrasubstituted oxindoles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The Diabetes Shared Care Program (DSCP) is an integrated care model in Taiwan to improve the care quality of patients with diabetes. Socioeconomic status (SES) is one of the important factors affecting health, and it is confirmed as a predictor of various diseases and deaths.This study aimed to determine the relationship between survival rate and SES among patients who participated in the DSCP., Methods: A cohort population-based study was conducted using the National Health Insurance Research Database of Taiwan from 2008 to 2013. The study subjects were type 2 diabetes. We defined individual SES and neighborhood SES by each patient's job category and household income, which were characterized as advantaged or disadvantaged. Then we compared the survival rates of SES groups by Cox proportional hazards model to adjust risk factors., Results: This study included 16 614 patients with type 2 diabetes who participated in the DSCP program. The DSCP cohort showed a high hospitalization rate in low individual SES. In terms of 10-year overall survival, DSCP participants with high individual SES living in advantaged and disadvantaged neighborhoods had lower risk of mortality than those with low SES living in advantaged and disadvantaged neighborhoods, after adjustment for age and comorbidity. DSCP participants with low individual SES living in disadvantaged neighborhoods had no significant difference of mortality as those with low individual SES living in advantaged neighborhoods., Conclusion: In this study, we found that low individual SES, but not neighborhood SES, was associated with an increased mortality rate among DSCP participants., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

A new approach for the total synthesis of the active stilbene dimer dehydro- δ -viniferin has been achieved in 9 steps with methyl 4-hydroxybenzoate and 3,5-dihydroxyacetophenone as starting materials. The key feature of the method is the amberlyst 15-mediated cyclodehydration of α-aryloxyketone. [Formula: see text].

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy (HAART) for human immunodeficiency virus type 1 (HIV-1) infection. In this study, we identified (+)-(7'S,8S,8'S)-3',4,4',5,5'-pentamethoxy-2,7'-cyclolignan (SG-1), a cyclolignan semi-synthesized from Machilus robusta and M. wangchiana extracts, as a potent NNRTI. SG-1 displayed anti-HIV-1 activity with an IC 50 of 0.77 μmol/L by inhibiting reverse transcriptase (RT) RNA-dependent DNA polymerase activity through a direct binding. It had synergistic effects when combined with tenofovir/lamivudine or zidovudine/lamivudine. The pharmacodynamics properties of SG-1 render it a valuable lead for the development of novel NNRTIs.

We present a low-density point eating algorithm for surface reconstruction from dense scans. First, the density map for each scan is estimated and the boundary densities are down-weighted. Subsequently, the poorly scanned low-density overlapping points are eaten up based on a user-specified threshold. Finally, the overlapping areas are thinned by using the moving least-squares operator and the homogeneous points are weighted averaged. The new algorithm can extract smooth but detailed point set surfaces that are as close as possible to the ground truth. The good performance of the new algorithm is demonstrated by comparison with several advanced surface reconstruction algorithms.

Dot-grid images are usually captured for grid strain analysis during sheet metal forming. Due to the strong reflective characteristic of the metallic surfaces, the recorded dot-grid images often have poor quality, low positioning accuracy, and low recognition rate. Therefore, an exposure-fusion-based dot-grid image acquisition and recognition approach is proposed. First, multiple dot-grid images are captured at different exposure levels. Subsequently, the recorded multi-exposure dot-grid images are fused into a new high-quality dot-grid image based on exposure fusion technology. Finally, a dot-grid image recognition procedure is developed to detect the dot-grids in the new dot-grid image. Both synthetic and real dot-grid images were tested to verify the performance of the novel approach. When synthetic dot-grid images were tested, the maximum positioning error was up to 6.044 pixels if they were recognized in the traditional way, whereas the maximum positioning error was reduced to 0.132 pixels if the novel approach was adopted. When real dot-grid images were tested, the lowest recognition rate is only 50.52% if they were recognized in the traditional way. Nevertheless, the recognition rate can reach about 91% if the novel approach was employed. These experimental results show the superiorities of the novel approach.

Biotransformation of trans -resveratrol and synthetic (±)-ε-viniferin in aqueous acetone using horseradish peroxidase and hydrogen peroxide as oxidants resulted in the isolation of two new resveratrol trimers ( 3 and 4 ), one new resveratrol derivative ( 5 ) with a dihydrobenzofuran skeleton, together with two known stilbene trimers ( 6 and 7 ), and six known stilbene dimers ( 8 - 13 ). Their structures and relative configurations were identified through spectral analysis and possible formation mechanisms were also discussed. Among these oligomers, trimers 6 and 7 were obtained for the first time through direct transformation from resveratrol. Results indicated that this reaction is suitable for the preparation of resveratrol oligomers with a complex structure., Competing Interests: The authors declare no conflict of interest.

Many naturally occurring oligostilbenes have drawn considerable attention because of their intricate structures and diverse biological activities. In recent years, oligostilbene bioactivities have become a popular research topic worldwide. Although these bioactivities are known to be extensive and several summaries on the activities of the compounds have been published, a comprehensive and systematic summary on active oligostilbenes is unavailable. From January 2005 to December 2013, a large number of active oligostilbenes and corresponding new bioactivities were reported in the literature. This review mainly focuses on the diverse bioactivities of oligostilbenes with various backbones.

Using potassium hexacyanoferrate (III)-sodium acetate as oxidant, the oxidative coupling reaction of isorhapontigenin and resveratrol in aqueous acetone resulted in the isolation of three new indane dimers 4, 6, and 7, together with six known stilbene dimers. Indane dimer 5 was obtained for the first time by direct transformation from isorhapontigenin. The structures and relative configurations of the dimers were elucidated using spectral analysis, and their possible formation mechanisms were discussed. The results indicate that this reaction could be used as a convenient method for the semi-synthesis of indane dimers because of the mild conditions and simple reaction products.

Three new cyanogenetic triglycosides linustatins A-C (1-3), and two new simple glycosides linustatins D and E (4 and 5) were isolated from the 70% ethanol extract of flaxseed meal (Linum usitatissimum L.). Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates showed moderate activities against aldose reductase and weak activities against α-glucosidase, DPP-IV, and FBPase at the same concentrations as the positive control drugs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT), because of its good targeting, minimal invasion, and safety, is becoming a very active area in cancer prevention and treatment, in which the photosensitizers have proved to be the core element for PDT. We developed a new HPLC method for analyzing porphyrin photosensitizers using Shiseido Capcell PAK C18 (150 mm x 4.6 mm, 5 µm) as the column at 30 °C, methanol-1% aqueous solution of acetic acid as the mobile phase in a flow rate of 1.0 mL · min(-1) in a gradient elution mode, and the detection wavelength at 380 nm. This method, showing good specificity, precision, accuracy and robusty via methodology validations, can be applied to the purity test and assay of porphyrin photosensitizers, and has played a key guide role in the R&D of the new porphyrin photosensitizer--sinoporphyrin sodium.

Overexpression of leukemia/lymphoma-related factor (LRF), which is an erythroid myeloid ontogenic factor protein, occurs in different cancers, including glioma. LRF is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of LRF knockdown on the regulation of glioma growth. LRF short hairpin RNA (shRNA) suppressed the expression of LRF protein in a glioma cell line (GL261-EGFP) compared to the negative control vector-transfected glioma cells. LRF knockdown also reduced glioma cell viability and enhanced cisplatin-induced apoptosis in glioma cells. AKT activation and the expression of various cell cycle-related genes were inhibited following LRF knockdown. The effect on growth and migration is related to dose response results of AKT and nuclear factor-kappa B (NF-κB) inhibitors. These data demonstrate that LRF may play a role in glioma progression, suggesting that inhibition of LRF expression using LRF shRNA should be further evaluated as a novel target for the control of glioma.

Objectives: To study the inhibitory effect of combining the gefitinib with cisplatin on tongue squamous cell carcinoma cells., Materials and Methods: Two cell lines were used, tca8113 which is a cisplatin-sensitive cell line, and tca8113/CDDP which is a cisplatin-resistant cell line established in Jiamusi University Laboratories. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to calculate the IC 50 values of both drugs using both cell lines. Detection of Ras, Raf and ERK1/2 was done by using western blot technique after exposure to different concentrations of gefitinib and cisplatin., Results: Tca8113/CDDP has shown more resistance to cisplatin than tca8113 and slightly more resistance to gefitinib than tca8113. Combination of the two drugs has shown to be more effective for both cell lines than when each alone even with lower concentrations., Conclusions: Combination of gefitinib and cisplatin is a better choice than using each drug alone.

One megastigmane derivative 1, one methyl jasmonate glycoside derivative 2, and two C-28 steroids with 3β,5β-cis-dihydroxyl conformation 3 and 4, together with eight known compounds 5-12 were isolated from the 70% ethanol extract of linseed meal (Linum usitatissimum L). Structures of 1-4 were elucidated by spectroscopic methods including NMR, HRESIMS, and Mo2(OAc)4-induced CD. The absolute configuration of 1 and 3 was determined by observing their induced circular dichroism after addition of Mo2(OAc)4 in DMSO. The absolute configuration of 2 was determined by NOESY experiment together with conformational analysis. The structure of 4a was corrected as 4 by an extensive analysis of its 1D and 2D NMR, in combination with the Mo2(OAc)4-induced CD in DMSO. The effect of all the isolates on nitric oxide (NO) generation by stimulated macrophages was evaluated, and none of them showed active., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Although basic medical studies have shown that lysophosphatidic acid (LPA) has an important relationship to activated blood platelets, we know little about this from clinical experience. This pilot study examined plasma LPA levels in patients with a risk of thrombotic events and evaluated the effects of aspirin on plasma LPA levels. In this basically cross-sectional study, we recruited 1352 patients with either hypertension or hyperlipidemia and 670 controls without any risk factors. Patients with risk factors had significantly higher plasma LPA levels than controls, the mean of LPA = 3.12 ± 2.24 vs. 2.57 ± 1.96 μmol/l, P < 0.001. The patients who had been taking aspirin had relatively lower plasma LPA levels compared with those who did not take aspirin, χ = 43.8, odds ratio (OR) [95% confidence interval (CI)] = 2.76 (2.03-3.75). For the hypertension group, χ = 23.1, OR (95% CI) = 3.44 (2.03-5.82), P < 0.001; for the hyperlipidemia group, χ = 22.9, OR (95% CI) = 2.53 (1.72-3.74), P < 0.001. Patients with a risk factor had higher plasma LPA levels compared with controls. Administration of aspirin may decrease elevated plasma LPA levels. This pilot clinical observation indicates that plasma LPA is worth to be studied further.

Aim: To investigate the effects of Vam3 (a resveratrol dimer extracted from Vitis amurensis Rupr) on cigarette smoke (CS)-induced cell apoptosis in lungs in vitro and in vivo and the underlying mechanisms of action., Methods: Human bronchial epithelial cell line BEAS-2B was exposed to cigarette smoke condensate (CSC, 300 mg/L), and cell apoptosis was determined using flow cytometry and Hoechst staining. Mitochondrial membrane potential was examined with TMRE staining. ROS and ceramide levels were detected with DCFH-DA fluorescence and HPLC-MS/MS, respectively. Cytochrome c release was detected using immunofluorescence. Caspase-9 and neutral sphingomyelinase 2 expression was measured with Western blotting. The breast carcinoma cell line MCF7 stably expressing GFP-tagged Bax was used to elucidate the role of mitochondria in CS-induced apoptosis. For in vivo study, male mice were exposed to CS for 5 min twice a day for 4 weeks. The mice were orally administered Vam3 (50 mg·kg(-1)·d(-1)) or resveratrol (30 mg·kg(-1)·d(-1)) each day 1 h before the first CS exposure., Results: Pretreatment of BEAS-2B cells with Vam3 (5 μmol/L) or resveratrol (5 μmol/L) significantly suppressed CSC-induced apoptosis, and prevented CSC-induced Bax level increase in the mitochondria, mitochondrial membrane potential loss, cytochrome c release and caspase-9 activation. Furthermore, pretreatment of BEAS-2B cells with Vam3 or resveratrol significantly suppressed CSC-stimulated intracellular ceramide production, and CSC-induced upregulation of neutral sphingomyelinase 2, the enzyme responsible for ceramide production in bronchial epithelial cells. Similar results were obtained in C6-pyridinium ceramide-induced apoptosis of GFP-Bax-stable MCF7 cells in vitro, and in the lungs of CS-exposed mice that were treated with oral administration of Vam3 or resveratrol., Conclusion: Vam3 protects bronchial epithelial cells from CS-induced apoptosis in vitro and in vivo by preventing mitochondrial dysfunction.

This study is to investigate the effect of Vam3, a dimeric derivative of resveratrol, on SNP-induced apoptosis and its potential mechanism in rat articular chondrocytes. Isolated rat articular chondrocytes were treated with sodium nitroprusside (SNP), a NO donor, to induce apoptosis. Apoptosis percentage was evaluated by Annexin V-PI and nucleus fracture was examined by DAPI staining. Level of intracellular reactive oxygen species (ROS) was detected using 2, 7'-dichlorofluorescin diacetate (DCFH-DA) as a fluorescence probe by fluorescence microplate reader. The change in mitochondrial membrane potential was detected by TMRE staining. Expressions of SIRT1, acetylated p53 (ac-p53), cleaved caspase 9 and cleaved caspase 3 were determined by Western blotting. It showed that Vam3 up to 10 micromol x L(-1) could significantly reduce SNP-induced rat articular chondrocytes apoptosis (P < 0.01) and nucleus fracture, inhibit the increase of intracellular ROS level (P < 0.01) and reverse the decrease in mitochondrial membrane potential (P < 0.01). Simultaneously, Vam3 could upregulate the expression of SIRT1, deacetylate p53, and inhibit the cleavage of caspase 9 and caspase 3 (P < 0.01) of rat articular chondrocytes exposed to SNP. This study indicates Vam3 could protect rat articular chondrocytes against SNP-induced apoptosis, perhaps through the upregulation of SIRT1 and deacetylation of p53.

The aim of this study was to analyze the association between pulse pressure and a novel type of phospholipid with solubility similar to that of lysophosphatidic acid (LPA), designated as AP, which was reported to be elevated during ischemia. In this cross-sectional study, 416 hypertensive patients and 252 controls aged between 35 and 70 years were enrolled consecutively. Fasting blood samples were extracted for assays of phospholipids and other biomarkers. Compared to controls, the hypertensive patients had higher levels of both LPA [odds ratio (OR) = 3.83] and AP (OR = 4.30). Changes in blood pressure did not affect the levels of LPA or AP. However AP, but not LPA, levels were significantly higher in patients with lower or higher pulse pressure (Pearson χ(2) = 11.239, P = 0.001). For patients whose pulse pressure was ≤60 mmHg, plasma levels of AP were significantly negatively correlated with pulse pressure. However, this was not observed for LPA and nine other biomarkers, including lipoproteins. Plasma levels of AP increased in hypertensive patients with higher or lower pulse pressure. Thus, attention should be paid to the possibility of cerebral ischemia in hypertensive patients when they have abnormal pulse pressure, especially for those with relatively low pulse pressure.

Synthetic isorhapontigenin was treated with several kinds of inorganic reagents and peroxidase so as to prepare active stilbene dimers. Among them, silver acetate in methanol gave two new isorhapontigenin dimers 4 and 5, together with four known natural stilbene dimers 2, 3, 6, and 7. Their structures and relative configurations were determined on the basis of spectral analysis, and their possible formation mechanisms were discussed, respectively. Compounds 2, 6, and 7 were artificially synthesized for the first time. All the products were evaluated for anti-inflammatory activities.

The Canadian Health Measures Survey, conducted between March 2007 and February 2009, revealed unmet dental needs among older adults in Canada. This article, the second of a 3-part series, explains that the inequity in oral care faced by elderly Canadians is due largely to the current fee-for-service dental service system. However, the inequity has arisen because of financial, behavioural and physical barriers, and both the community at large and the dental profession have a social responsibility to reduce this unfairness and provide equitable access to oral care for older people.

A metal-free [3 + 2 + 1]/[2 + 2 + 1] biscyclization strategy has been developed for the stereospecific construction with concomitant derivation of biologically significant indolizin-5(1H)-ones from simple and commercial starting materials. The transformations are notable because they can yield five new σ bonds and six stereocenters including a quaternary carbon center in a single operation.

Three-component reaction of aldehyde, 1H-indazol-6-amine and 1,3-dicarbonyl compounds in EtOH under catalyst-free conditions, generates the corresponding pyrazolo[3,4-a]acridine, cyclopenta[b]pyrazolo[3,4-f]quinoline, indeno[1,2-b]pyrazolo[3,4-f]quinoline and benzo[h]pyrazolo[3,4-a]acridine derivatives in high yields and regioselectivity, respectively. The dicarbonyl compounds include 5,5-dimethylcyclohexane-1,3-dione, cyclopentane-1,3-dione, 2H-indene- 1,3-dione and 2-hydroxynaphthalene-1,4-dione.

This study compared the effects of carbamide peroxide (CP) and chlorhexidine (CHX) on oral biofilm in vitro. Collagen-coated hydroxyapatite discs were inoculated with subgingival plaque. After 3 weeks, the emergent biofilms were subjected to 1-, 3-, and 10-min exposures of a 1% CHX gel, a 5% CP gel and rinse, and a 10% CP gel and rinse. Subsequently, the biofilms were stained using a two-colour fluorescent dye kit for confocal laser scanning microscopy, and the volume ratio of dead bacteria to all bacteria was analysed. Compared to a non-treated gel control, the active agents killed bacteria on all the discs, with higher concentration and longer exposure times killing more bacteria. The rinse form disrupted the biofilm quicker than the gel form. Overall, 10% CP showed more disruption of biofilm and a greater proportion of killed bacteria than 1% CHX (p<0.05).

Ten compounds were isolated from the 70% ethanol extract of linseed meal (Linum usitatissimum L) through a combination of various chromatographic techniques, including silica gel, macroporous adsorbent resin, Sephadex LH-20, and preparative HPLC. On the basis of spectroscopic data analysis, they were elucidated as 1-methylethyl-2-O-beta-D-glucopyranosyl-(1" --> 6')-beta-D-glucopyanoside (1), linustatin (2), neolinustatin (3), lotaustralin (4), linamarin (5), deoxyguanosine (6), deoxyadenosine (7), (+)-pinoresinol-4'-O-beta-D-glucopyranoside (8), 4-O-beta-D-glucopyranosylvanillyl alcohol (9) and tachioside (10), separately. Among them, compound 1 is a new compound, and compounds 6, 8 and 10 were isolated from the linseed meal for the first time.

One new stilbene dimer named amurensin O (1), together with one known resveratrol trimer melapinol B (2), was isolated from Vitis amurensis, and their structures were identified on the basis of spectral analysis, especially 2D NMR spectral analysis.

Oral health is a contributory factor to general well-being and quality of life. The Canadian Health Measures Survey between March 2007 and February 2009, documented the oral problems that elderly people experience. This age group faces inequity in oral health care (especially in a fee-for-service system) and the aging of the Canadian population will exacerbate the problem of inequity. This article, the first of a 3-part series, discusses the impact of poor oral health on elderly people. The second article will consider inequity in terms of the financial, behavioural and physical barriers within the Canadian health care system, as well as ethical considerations related to this inequity, and the third will provide suggestions to overcome the barriers.

A novel multicomponent strategy for the efficient synthesis of tricyclic pyrrolo[1,2-a]quinolines has been described. The bond-forming efficiency, accessibility and generality of this synthesis make it highly attractive to assemble tri-heterocyclic scaffolds.

Aim: To appraise the efficacy of Vam3 (Amurensis H), a dimeric derivative of resveratrol, at inhibiting cigarette smoke-induced autophagy., Methods: Human bronchial epithelial cells were treated with cigarette smoke condensates, and a chronic obstructive pulmonary disease (COPD) model was established by exposing male BALB/c mice to cigarette smoke. The protein levels of the autophagic marker microtubule-associated protein 1A/1B-light chain 3 (LC3), Sirtuin 1 (Sirt1), and foxhead box O 3a (FoxO3a) were examined using Western blotting and Immunohistochemistry. LC3 punctae were detected by immunofluorescence. The levels of FoxO3a acetylation were examined by immunoprecipitation. The level of intracellular oxidation was assessed by detecting ROS and GSH-Px., Results: Vam3 attenuated cigarette smoke condensate-induced autophagy in human bronchial epithelial cells, and restored the expression levels of Sirt1 and FoxO3a that had been reduced by cigarette smoke condensates. Similar protective effects of Vam3, reducing autophagy and restoring the levels of Sirt1 and FoxO3a, were observed in the COPD animal model. Additionally, Vam3 also diminished the oxidative stress that was induced by the cigarette smoke condensates., Conclusion: Vam3 decreases cigarette smoke-induced autophagy via up-regulating/restoring the levels of Sirt1 and FoxO3a and inhibiting the induced oxidative stress.

Deaf people encounter barriers to accessing cancer information. In this study, a graphically enriched educational video about cervical cancer was created in American Sign Language, with English open captioning and voice overlay. Deaf (n = 127) and hearing (n = 106) women completed cancer knowledge surveys before and after viewing the video. Hearing women yielded higher scores before the intervention. Both groups demonstrated a significant increase in general and cervical cancer knowledge after viewing the video, rendering posttest knowledge scores nearly equal between the groups. These findings indicate that this video is an effective strategy for increasing cervical cancer knowledge among deaf women.

A new resveratrol trimer derivative, named as gnetubrunol A (1), together with five known stilbene derivatives, shegansu B (2), resveratrol (3), isorhapontigenin (4), gnetifolin E (5), and isorhapontigenin-11-O-β-d-glucopyranoside (6) were isolated from the lianas of Gnetum brunonianum Griff. Their structures were elucidated on the basis of spectral analysis (UV, IR, MS, (1)H NMR, (13)C NMR, and 2D NMR). The anti-inflammatory activities of 1, 5, and 6 have also been assayed.

In the title compound, [Mn(C(6)H(4)N(5)O)(2)(H(2)O)(2)]·2H(2)O, the Mn(II) ion is situated on an inversion centre and is coordinated by the O and N atoms of two bis-chelating 5-(2-pyridyl-1-oxide)tetra-zolate ligands and two O atoms of two water mol-ecules in a distorted octa-hedral geometry. All the water H atoms are involved in O-H⋯N and O-H⋯O hydrogen bonds with uncoordinated water O atoms and tetra-zole N atoms, which link the mol-ecules into a three-dimensional network.

The aim of the present study is to investigate the effects of Vam3 which is one of the dihydroxystilbene compounds on expressions of ICAM-1 in the lungs of OVA-induced asthmatic mice and the mechanisms of anti-airway inflammation. Balb/c mice were challenged with OVA inhalation. Lung tissues were stained with Mayer's hematoxylin and eosin for histopathologic examination. The expression of ICAM-1 in the lungs of mice was analyzed by Western blotting and immunohistochemistry method. The NF-kappaB activities were detected by NF-kappaB-luc reporter genetic transient transfection method. The activities of MMP-9 induced by LPS, TNF-alpha and PMA in THP-1 cells were determined by gelatin zymography method. The results showed that Vam3 could inhibit the expression of ICAM-1 in the OVA-induced mouse model. In addition, Vam3 could significantly suppress the activities of NF-kappaB in A549 cells and MMP-9 in THP-1 cells induced by LPS, TNF-alpha and PMA. These results suggested that Vam3 could alleviate the asthmatic inflammation by decreasing ICAM-1 expression in asthmatic mice, down regulating NF-kappaB and MMP-9 activities. Compound Vam3 showed inhibitory effects on inflammatory signal pathways involved in asthma.

In the title compound, C(15)H(12)ClF(3)N(4)O(2), the dihydro-pyrimidine ring exhibits an envelope conformation. The dihedral angle between the mean planes of the dihydro-pyrimidine and phenyl rings is 83.94 (6)°. The OCH(2)CH(3) group is disordered over two sites with occupancies of 0.155 (3) and 0.845 (3). The crystal packing is stabilized by inter-molecular N-H⋯N hydrogen bonds.

In the title compound, C(14)H(11)BrF(3)N(5)O(2), the pyrimidine ring adopts a flattened envelope conformation with sp(3)-hybridized carbon as the flap [deviation = 0.177 (3) Å]. The dihedral angle between tetra-zole and bromo-phenyl rings is 84.3 (1)°. In the crystal, mol-ecules are linked into centrosymmetric dimers by pairs of N-H⋯N hydrogen bonds.

In the title compound, C(15)H(11)N(3)O(4)S, the dihedral angle between the mean planes of the dihydro-indol-2-one (r.m.s. deviation = 0.015 Å) and dihydro-thieno[3,2-b]pyran (r.m.s. deviation = 0.011 Å) ring systems is 89.53 (3)°. The crytal packing is consolidated by inter-molecular N-H⋯O and N-H⋯N hydrogen bonds, which link the mol-ecules into a two-dimensional network into sheets lying parallel to (100).

A simple and efficient method for the combinatorial synthesis of highly substituted thiopyrano[3,4-b]pyridin-5(4H)-one, thiopyrano[3,4-b]quinoline-4,6(3H,5H)-dione, dithiopyrano[3,4-b:4',3'-e]pyridine-4,6(1H,3H)-dione, and pyrazolo[3,4-b]thiopyrano[4,3-e]pyridin-5(1H)-one derivatives has been developed. The synthesis was achieved via one-pot multicomponent reaction of aromatic aldehyde, 2H-thiopyran-3,5(4H,6H)-dione and enamine (such as the derivatives of amine and 1,3-dicarbonyl compounds and 3-methyl-1-phenyl-1H-pyrazol-5-amine) in glacial acetic acid. This procedure features short reaction time, generally good to excellent yields, easily available starting materials, and operational simplicity. This chemistry provides an efficient and promising synthetic strategy to diversity-oriented construction of the thiopyrano[3,4-b]pyridine skeleton.

The title compound, C(14)H(11)ClN(2)O(3)S, with fused thiophene and pyran rings, was synthesized via the condensation of dihydro-thio-phen-3(2H)-one 1,1-dioxide and 2-(3-chloro-benz-yl-idene)malononitrile catalysed by triethyl-amine in ethanol. The thio-phene ring adopts an envelope conformation and the pyran ring is planar (r.m.s. deviation = 0.0067 Å). The dihedral angle between the pyran and phenyl rings is 80.8 (1)°. The crystal packing is stabilized by inter-molecular N-H⋯N and N-H⋯O hydrogen bonds in which the cyano N and sulphone O atoms, respectively, acting as acceptors.

In the title compound, C(14)H(11)BrN(2)O(3)S, the 2,3-dihydro-thio-phene ring is almost planar [maximum deviation = 0.006 (1) Å]. The pyran ring is in an envelope conformation [puckering parameters Q = 0.115 (2) Å, θ = 77.5 (10), ϕ = 172.9 (10)°]. The pyran and phenyl rings are approximately perpendicular, making a dihedral angle of -76.4 (2)°. The crystal packing is stabilized by inter-molecular N-H⋯O hydrogen bonds, with the sulfone O atoms acting as acceptors.

Objective: To investigate the correlation between length of hypertension history with plasma level of A Phospholipids Component with the Similar Solubility of Lyso-Phosphatidic Acid (APCSSLPA or briefly AP). So that to farther understand the changes accompanied with prolongation of hypertension history., Methods: This is a small cross-sectional study. 170 patients with primary hypertension and 79 normal controls without hypertension history were enrolled. The lengths of case history were recorded and compared with their plasma levels of AP. Similar study were also conducted on other 11 clinical makers as references., Results: AP correlated significantly with the length of hypertension history. Correlation coefficient beta is 0.186, P = 0.015. But AP did not correlated significantly with systolic or diastolic pressure of patients. The age of patients did not correlated with AP either (beta = 0.027, P = 0.71). The patient's number with middle or high level of AP was significantly larger in the group in which hypertension history was 10 years or more, than in the group in which hypertension history was less then 10 years. chi(2) = 6.51, P = 0.012. OR = 2.444, 95%CI = 1.219 - 4.903. However, lysophosphatidic acid and other 10 bio-makers which often be used in cerebrovascular and cardiovascular diseases, such as blood lipid, blood sugar, different kinds of lipoprotein and D-dimer etc. did not correlated significantly with hypertension history., Conclusion: Comparing with 11 clinical makers, AP was the only one correlated with the length of hypertension history. Our findings suggest: the prolongation of hypertension history may accompanied with increased oxidative damages. The patients with prolonged hypertension history should prevent this possible threaten. Furthermore, AP is a very promising marker with unique worth in cardiovascular and cerebrovascular diseases.

A new triglucosylated naphthalene derivative, named aloveroside A (1), together with two known anthraquinone dimers and two 6-phenyl-2-pyrone derivatives, was isolated from the Aloe vera ethanolic extracts. The structure of 1 was established as 1-(((4-(1-O-beta-D-glucopyranosyl -(1-->4)-beta-D-xylopyranoside)-hydroxymethyl)-1-hydroxy-8-O-alpha-L-rhamnopyranoside)naphthalene-2-yl)-ethanone by means of spectroscopic evidences and chemical methods. All these compounds were tested for their BACE inhibitory activity but no significant activities were found.