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Background: This report describes emergency response following an imported vaccine derived poliovirus (VDPV) case from Myanmar to Yunnan Province, China and the cross-border collaboration between China and Myanmar. Immediately after confirmation of the VDPV case, China disseminated related information to Myanmar with the assistance of the World Health Organization., Methods: A series of epidemiological investigations were conducted, both in China and Myanmar, including retrospective searches of acute flaccid paralysis (AFP) cases, oral poliovirus vaccine (OPV) coverage assessment, and investigation of contacts and healthy children., Results: All children <2 years of age had not been vaccinated in the village where the VDPV case had lived in the past 2 years. Moreover, most areas were not covered for routine immunization in this township due to vaccine shortages and lack of operational funds for the past 2 years., Conclusions: Cross-border collaboration may have prevented a potential outbreak of VDPV in Myanmar. It is necessary to reinforce cross-border collaboration with neighboring countries in order to maximize the leverage of limited resources.

Three new dihydroisocoumarin glucosides, termed periplanosides A-C (1-3), a known analog, pericanaside (4), and the other twenty known compounds were isolated from the insect Periplaneta americana. Their structures including absolute configurations were determined by comprehensive spectroscopic analyses and computational methods. Biological evaluation showed that compound 2 could stimulate collagen production by 31.2% in human dermal fibroblasts-adult (HDFa) at the concentration of 30 μM, indicating its significance in skin repair and ulcer.

Two new dopamine derivatives divesamides A (1) and B (2), along with six known N-containing compounds were isolated from the Chinese black ant (Polyrhachis dives). Their structures were determined on the basis of spectroscopic methods. Compound 1 is a racemate, and chiral HPLC separation yielded a pair of antipodes. The absolute configuration of (+)-1 was assigned by a computational method. The double signals in the (1)H and (13)C NMR spectra of 2 that resulted from the presence of a formamide group were discussed. The T- and B-lymphocytes proliferation assay showed that 2 has moderate immunosuppressive activity toward T- and B-lymphocytes proliferation at a concentration of 20 μM.

Glucuronidation reaction of trifluoperazine (TFP) is a typical probe reaction to phenotype the activity of UDP-glucuronosyltransferase 1A4. The present study aims to compare the metabolic behavior of TFP in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. In vitro human liver microsome incubation system was used. The Eadie-Hofstee plot was used to determine the kinetic type. The results showed that the data for human liver microsomes (HLMs) and monkey liver microsomes (MyLMs)-catalyzed glucuronidation were best fit to the substrate inhibition model. For the metabolism of TFP in HLMs, the kinetic parameters were calculated to be 40 ± 5 and 140 ± 20 μM for K m and K si values, respectively. For the MyLM-mediated metabolism of TFP, the K m and K si values were calculated to be 108 ± 10 and 250 ± 30 μM, respectively. The same metabolic kinetic type and different kinetic parameters were demonstrated for the metabolism of TFP between HLMs and MyLMs. All these data were helpful for understanding the metabolism difference of TFP between human and monkey.

Background and Aim: The relationships between dietary nuts and legume intake and risk of stroke are inconsistent. We summarized the evidence by a meta-analysis of prospective cohort studies., Methods and Results: We systematically searched the MEDLINE and EMBASE databases up to 31 January 2014. Random-effects models were used to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using the Cochran's Q and I(2) statistics. Eight prospective studies with a total of 468,887 subjects and 10,493 stroke events were included in the meta-analysis. Overall, a diet containing greater amounts of legumes may be not associated with a lower risk of stroke (SRR = 0.95, 95% CI: 0.84-1.08; P(heterogeneity) = 0.091, I(2) = 43.2%); however, a diet containing greater amounts of nuts may be associated with a lower risk of stroke (SRR = 0.90, 95% CI: 0.81-0.99; P(heterogeneity) = 0.527, I(2) = 0). Gender significantly modified the effects of nut consumption on stroke risk, and high nut intake was associated with reduced risk of stroke in women (SRR = 0.85, 95% CI: 0.75-0.97) other than in men (SRR = 0.95, 95% CI: 0.82-1.11)., Conclusion: The current meta-analysis provides some evidences for the hypothesis that high intake of dietary nut was inversely associated with stroke risk, whereas dietary legumes intake was not associated with stroke risk., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Somatic cell genetics is a powerful approach for unraveling the regulatory mechanism of cholesterol metabolism. However, it is difficult to identify the mutant gene(s) due to cells are usually mutagenized chemically or physically. To identify important genes controlling cholesterol biosynthesis, an unbiased forward genetics approach named validation-based insertional mutagenesis (VBIM) system was used to isolate and characterize the 25-hydroxycholesterol (25-HC)-resistant and SR-12813-resistant mutants. Here we report that five mutant cell lines were isolated. Among which, four sterol-resistant mutants either contain a truncated NH2-terminal domain of sterol regulatory element-binding protein (SREBP)-2 terminating at amino acids (aa) 400, or harbor an overexpressed SREBP cleavage-activating protein (SCAP). Besides, one SR-12813 resistant mutant was identified to contain a truncated COOH-terminal catalytic domain of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). This study demonstrates that the VBIM system can be a powerful tool to screen novel regulatory genes in cholesterol biosynthesis.

Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

A novel series of chalcone derivatives (4a-8d) were designed, synthesized, and evaluated for the inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The logP values of the compounds were shown to range from 1.49 to 2.19, which suggested that they were possible to pass blood brain barriers in vivo. The most promising compound 4a (IC50: 4.68 μmol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 μmol/L) and showed a high selectivity for AChE over BuChE (ratio: 4.35). Enzyme kinetic study suggested that the inhibition mechanism of compound 4a was a mixed-type inhibition. Meanwhile, the result of molecular docking showed its potent inhibition of AChE and high selectivity for AChE over BuChE., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aims: In this study, we aim to summarise our experience with techniques used for the transcatheter retrieval of embolised devices., Methods: We retrospectively reviewed the transcatheter retrieval of embolised devices in seven patients who underwent an attempted transcatheter closure of perimembranous ventricular septal defects (PMVSDs) between October 2002 and October 2013. The incidence, the main causes for the device's embolisation, and the techniques for transcatheter retrieval of the embolised device are discussed., Results: The incidence of device embolisation in our centre was 0.82% (seven embolisations in 852 device placements). The main causes for device embolisation included undersized devices and inadequate subaortic rims. Among the seven embolisations, six of the devices were retrieved percutaneously without mortality, while one was retrieved during surgery. Of these patients, five had a HeartR(TM) Membranous VSD occluder of their PMVSDs, and the remaining two had surgical PMVSD closures., Conclusions: Our approach to the transcatheter retrieval of the embolised devices is associated with good results., (Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Purpose: It is widely acknowledged that teachers are at greater risk of work-related health problems. At the same time, employee perceptions of different dimensions of organizational climate can influence their attitudes, performance, and well-being at work. This study applied and extended a safety climate model in the context of the education sector in Hong Kong. Apart from safety considerations alone, the study included occupational health considerations and social capital and tested their relationships with occupational safety and health (OSH) outcomes., Methods: Seven hundred and four Hong Kong teachers completed a range of questionnaires exploring social capital, OSH climate, OSH knowledge, OSH performance (compliance and participation), general health, and self-rated health complaints and injuries. Structural equation modeling (SEM) was used to analyze the relationships between predictive and outcome variables., Results: SEM analysis revealed a high level of goodness of fit, and the hypothesized model including social capital yielded a better fit than the original model. Social capital, OSH climate, and OSH performance were determinants of both positive and negative outcome variables. In addition, social capital not only significantly predicted general health directly, but also had a predictive effect on the OSH climate-behavior-outcome relationship., Conclusions: This study makes a contribution to the workplace social capital and OSH climate literature by empirically assessing their relationship in the Chinese education sector.

Semisynthetic analogues of the natural product 1-O-acetylbritannilactone (ABL), a sesquiterpene isolated from the medicinal plant Inula britannica, have been prepared and exhibited significant in vitro cytotoxic activities against four cell lines including three human cancer cell lines (HCT116, HEp-2 and HeLa) and one normal hamster cell line (CHO). Structure-activity relationships indicate that esterification of 6-OH (enhanced lipophilicity) and α-methylene-γ-lactone functionalities play important roles in conferring cytotoxicity. Among the tested compounds, 14 bearing a lauroyl group (12C) at the 6-OH position displayed most potent in vitro cytotoxic activity, with IC50 values between 2.91 and 6.78 μM, comparable to the positive control etoposide (VP-16, IC50 values between 2.13 and 4.79 μM). Moreover, the compound 14 triggered remarkable apoptosis at a low concentration, and induced cell cycle arrest in G2/M phase in HCT116 cells. The biological assays conducted with normal cells (CHO) revealed that all the synthetic compounds are no selective against cancer cell lines tested., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Carbonic anhydrase IX (CA IX), a hypoxia-inducible protein in tumors, has been shown to be valuable for the prognosis of nasopharyngeal carcinoma (NPC). However, the function and mechanism of CA IX has been not explored in NPC. Here, we found that CA IX was detected at higher levels in NPC cells and tissues than their corresponding partners. Furthermore, the cell growth, migration and invasion in vitro were altered with shRNA or overexpression of CA IX in NPC cells. More importantly, the metastatic ability of NPC cells stably expressing CA IX was significantly enhanced using the hepatic metastasis model of nude mice in vivo. Finally, the mTOR pathway was indicated to be involved in such effects of CA IX on NPC. This is the first evidence that CA IX may promote the NPC metastasis to potentially be a therapeutic target for NPC, and that the inhibitory molecules of CA IX and/or the mTOR pathway alone or combination with both may be worth to have a clinical trial for the patients with NPC.

In preceding studies, cultivation of Chaetomium globosum, an endophytic fungus in Ginkgo biloba, produced five cytochalasan mycotoxins, chaetoglobosins A, G, V, Vb, and C (1-5), in three media. In the present work, five known chaetoglobosins, C, E, F, Fex, and 20-dihydrochaetoglobosin A (5-9), together with the four known compounds (11-14), were isolated from the MeOH extracts of the solid culture of the same endophyte. The structures of these metabolites were elucidated on the basis of spectroscopic analysis. Treatment of chaetoglobosin F (7) with (diethylamino)sulfur trifluoride (DAST) in dichloromethane afforded an unexpected fluorinated chaetoglobosin, named chaetoglobosin Fa (10), containing an oxolane ring between C-20 and C-23. The phytotoxic effects of compounds 1, 3-8, and 10 were assayed on radish seedlings; some of these compounds (1, 3, and 6-8) significantly inhibited the growth of radish (Raphanus sativus) seedlings with inhibitory rates of >60% at a concentration of 50 ppm, which was comparable or superior to the positive control, glyphosate. In addition, the cytotoxic activities against HCT116 human colon cancer cells were also tested, and compounds 1 and 8-10 showed remarkable cytotoxicity with IC50 values ranging from 3.15 to 8.44 μM, in comparison to the positive drug etoposide (IC50 = 2.13 μM). The epoxide ring between C-6 and C-7 or the double bond at C-6(12) led to a drastically increased cytotoxicity, and chaetoglobosin Fa (10) displayed a markedly increased cytotoxicity but decreased phytotoxicity.

Two new metabolites, an α-pyridone derivative, 3-hydroxy-2-methoxy-5-methylpyridin-2(1H)-one (1), and a ceramide derivative, 3-hydroxy-N-(1-hydroxy-3-methylpentan-2-yl)-5-oxohexanamide (2), and a new natural product, 3-hydroxy-N-(1-hydroxy-4-methylpentan-2-yl)-5-oxohexanamide (3), along with 15 known compounds including chaetoglobosin C (7) and chaetoglobosin F (8) were isolated from the solid culture of the endophytic fungus Botryosphaeria dothidea KJ-1, collected from the stems of white cedar (Melia azedarach L). The structures were elucidated on the basis of spectroscopic analysis (1D and 2D NMR experiments and by mass spectrometric measurements), and the structure of 1 was confirmed by X-ray single-crystal diffraction. These metabolites were evaluated in vitro for antimicrobial, antioxidant, and cytotoxicity activities. Pycnophorin (4) significantly inhibited the growth of Bacillus subtilis and Staphyloccocus aureus with equal minimum inhibitory concentration (MIC) values of 25 μM. Stemphyperylenol (5) displayed a potent antifungal activity against the plant pathogen Alternaria solani with MIC of 1.57 μM comparable to the commonly used fungicide carbendazim. Both altenusin (9) and djalonensone (10) showed markedly DPPH radical scavenging activities. In addition, stemphyperylenol (5) and altenuene (6) exhibited strong cytotoxicity against HCT116 cancer cell line with a median inhibitory concentration (IC50) value of 3.13 μM in comparison with the positive control etoposide (IC50 = 2.13 μM). This is the first report of the isolation of these compounds from the endophytic B. dothidea.

Objective: To investigate the expression of hepatic Toll-like receptor 1 (TLR1), TLR2 and TLR6 on mice with Schistosoma japonicum infection., Methods: Fifty BALB/c mice were infected with 20 +/- 3 S. japonicum cercariae through abdominal skin. At 6 weeks post-infection, the mice (n = 10) in treatment group were administered intragastrically with praziquantel [250 microg/(g x d)] for 3 d. The livers of mice (n = 10) were collected at pre-infection and 5, 6, 8 and 12 weeks post-infection, and then the mRNA expression levels of hepatic TLR1, TLR2, TLR6 gene were detected with reverse transfer PCR. Hepatic TLR2, TLR6 protein levels were detected by immunohistochemical staining., Results: The mRNA levels of TLR1, TLR2, and TLR6 on 5, 6, 8 and 12 weeks post infection were significantly higher than that of uninfected mice. After praziquantel treatment, the mRNA level of TLR2 and TLR6 in murine liver of treatment group was lower than that of infection group, but the level of TLR1 mRNA had no obvious change. Furthermore, immunohistochemistry results revealed that the expression of TLR2 and TLR6 proteins in murine liver was up-regulated at 5, 6, 8 and 12 weeks post-infection. After praziquantel treatment, the percentage of TLR2 positive area in liver of infected mice without and with praziquantel treatment were (44.2 +/- 4.3)%, (8.8 +/- 3.1)%, respectively, and TLR2 protein level was considerably down-regulated (P < 0.01). The percentage of TLR6 positive area in liver of infected mice without and with praziquantel treatment was (48.4 +/- 5.4)%, (37.4 +/- 3.5)%, respectively, and TLR6 level decreased slightly (P < 0.05)., Conclusion: The expression level of TRL2 and TLR6 in murine liver increases after Schistosoma japonicum infection. While compared with TLR2, the role of TLR6 in this progress is a weaker one.

We report the construction of two Bacillus subtilis expression vectors, pBNS1/pBNS2. Both vectors are based on the strong promoter P43 and the ampicillin resistance gene expression cassette. Additionally, a fragment with the Shine-Dalgarno sequence and a multiple cloning site (BamHI, SalI, SacI, XhoI, PstI, SphI) were inserted. The coding region for the amyQ (encoding an amylase) signal peptide was fused to the promoter P43 of pBNS1 to construct the secreted expression vector pBNS2. The applicability of vectors was tested by first generating the expression vectors pBNS1-GFP/pBNS2-GFP and then detecting for green fluorescent protein gene expression. Next, the mannanase gene from B. pumilus Nsic-2 was fused to vector pBNS2 and we measured the mannanase activity in the supernatant. The mannanase total enzyme activity was 8.65 U/ml, which was 6 times higher than that of the parent strain. Our work provides a feasible way to achieve an effective transformation system for gene expression in B. subtilis and is the first report to achieve B. pumilus mannanase secretory expression in B. subtilis.

Background: Transcatheter closure (TCC) of ruptured sinus of Valsalva aneurysm (RSVA) is an alternative strategy to surgery, but there is a lack of long-term outcome data. METHODS AND RESULTS: From 2004 to 2012, 17 patients (8 males, 9 females) were treated with patent ductus arteriosus (PDA) occluders by antegrade venous approach and were followed for 18-102 months. Of the 17 patients, transthoracic echocardiography revealed rupture of the right coronary sinus into the right ventricle in 9 and into the right atrium in 4, and noncoronary sinus rupture into the right ventricle in 3 and into the right atrium in 1. Most (10/17) were in New York Heart Association (NYHA) functional class III or IV. Aortography showed that the size of the defect was 7.71±2.84 mm (4-15 mm). TCC was attempted using PDA occluders 2-5 mm larger than the aortic end of the defects. The device sizes ranged from 8/6 to 18/16 mm (median, 10/8 mm). The procedure was successful in 16 (94.1%), and all of them had complete occlusion at discharge. On a median follow-up of 42 months, 14 patients were in NYHA class I and 2 were in class II, and there was no residual shunt, device embolization, infective endocarditis, or aortic regurgitation., Conclusions: TCC of RSVA is a safe and effective alternative to surgery with favorable long-term follow-up results.

To investigate the epidemic and evolutionary trends of enterovirus (EV) in the external environment of Yunnan Province, China, molecular typing was performed on 4 EV strains that were isolated from environmental sewage in Yunnan. The VP1 region of isolates was amplified by RT-PCR using universal enterovirus primers, and the amplified VP1 region was sequenced for GenBank BLAST search and genotype analysis. The 4 EV strains were identified as ECHO7. Their nucleotide and amino acid homologies with the VP1 sequences of 68 ECHO7 strains retrieved from GenBank were measured by Mega software analysis. Our findings showed that ECHO7 strains from environmental sewage and population samples were in different evolutionary branches. These strains showed typical geographical and temporal differences; In addition, there were different transmission chains at the same time and in the same area. ECHO7 strains isolated from sewage water and patients with acute flaccid paralysis during the same period in Yunnan belonged to different clusters and evolved at different speeds. Special concerns are needed for this problem. Continuous molecular biological surveillance of human EV in the external environment of Yunnan will provide strong support for early warning of EV diseases.

Background: The current military conflicts in Iraq and Afghanistan have resulted in the most US casualties since the Vietnam War. Previous research on the association between deployment-related injury and posttraumatic stress disorder (PTSD) has yielded mixed results., Objectives: To examine the effect of battle injury (BI) relative to non-battle injury (NBI) on the manifestation of PTSD symptoms in military personnel and to assess the demographic, injury-specific, and pre-injury factors associated with PTSD following a BI., Patients and Methods: A total of 3403 personnel with deployment-related injury (1777 BI and 1626 NBI) were identified from the Expeditionary Medical Encounter Database. Records were electronically matched to Post-Deployment Health Assessment (PDHA) data completed 1-6 months post-injury. The PTSD screening outcome was identified using a four-item screening tool on the PDHA., Results: Compared to those with NBI, personnel with BI had more severe injuries, reported higher levels of combat exposure, and had higher rates of positive PTSD screen. After adjusting for covariates, personnel with BI were twice as likely to screen positive for PTSD compared to those with NBI (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.60-2.75). In multivariable analysis among battle-injured personnel only, moderate and serious-severe injury (OR, 1.49; 95% CI, 1.12-2.00 and OR, 1.64; 95% CI, 1.01-2.68, respectively), previous mental health diagnosis within 1 year of deployment (OR, 2.69; 95% CI, 1.50-4.81), and previous BI (OR, 1.96; 95% CI, 1.22-3.16) predicted a positive PTSD screen., Conclusions: Military personnel with BI have increased odds of positive PTSD screen following combat deployment compared to those with NBI. Post-deployment health questionnaires may benefit from questions that specifically address whether service members experienced an injury during combat., (Published by Elsevier Ltd.)

Fourteen novel steroidal C-17 pyrazolinyl derivatives 9a-g and 10a-g were synthesized from commercially available progesterone and tested for their cytotoxic activity against brine shrimp (Artemia salina) and three human cancer cell lines (NCI-H460, HeLa, and HepG2). Some of these synthetic compounds exhibited significant cytotoxic activity, and treatment of HeLa cells with compound 10b resulted in the cell population arrest in the S phase. A structure-activity relationship was discussed., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Aim: To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency on the cytotoxicity of chemotherapeutic agents toward colorectal cancer cells., Methods: PTEN-deficient colorectal cancer (CRC) cells were generated by human somatic cell gene targeting using the adeno-associated virus system. The cytotoxic effects of compounds including curcumin, 5-fluorouracil (5-FU), dihydroartemisinin (DHA), irinotecan (CPT-11) and oxaliplatin (OXA) on cancer cells were determined using the MTT assay. Enhanced cytotoxicity of curcumin in PTEN-deficient CRC cells was observed, and this was confirmed using clonogenic assays. Apoptosis and cell cycle progression were analyzed by flow cytometry. Levels of apoptosis and cell cycle-related proteins were examined by Western blotting., Results: We developed an isogenic set of CRC cell lines that differed only in their PTEN status. Using this set of cell lines, we found that disruption of the PTEN gene had no effect on the sensitivity of CRC cells to 5-FU, CPT-11, DHA, or OXA, whereas PTEN disruption increased the sensitivity of CRC cells to curcumin. Loss of PTEN did not alter the curcumin-induced apoptosis in CRC cells. However, PTEN deficiency led to an altered pattern of curcumin-mediated cell cycle arrest. In HCT116 PTEN (+/+) cells, curcumin caused a G2/M phase arrest, whereas it caused a G0/G1 phase arrest in HCT116 PTEN (-/-) cells. Levels of cell cycle-related proteins were consistent with these respective patterns of cell cycle arrest., Conclusion: Curcumin shows enhanced cytotoxicity toward PTEN-deficient cancer cells, suggesting that it might be a potential chemotherapeutic agent for cancers harboring PTEN mutations.

Objective: To observe the relative activity of sperm mitochondria and the proportion of ROS-positive sperm before and after capacitation and progesterone (Pg)-induced hyperactivation, and investigate the functional characteristics of sperm mitochondria., Methods: We collected 20 samples of normal human spermatozoa that met the criteria of WHO Laboratory Manual for the Examination and Processing of Human Semen (5th ed) and cultured them with the swim-up method in a CO2 incubator at 37 degrees C for 1 hour. We divided the sperm into a pre-capacitation and a capacitated group, and further incubated the capacitated sperm in an upright tube with (Pg-induced group) or without (control group) slow-releasing Pg at 37 degrees C for another hour. Then we determined the relative activity of mitochondria and the percentage of ROS-positive cells in the sperm samples using JC-1 and DCF staining., Results: The relative activities of mitochondria were significantly increased in the capacitated, control and Pg-induced groups (6.23, 14.36 and 12.33) as compared with the pre-capacitation group (1.42) (P < 0.05), while the percentages of balanced mitochondria (mitochondria with equal amount of high and low electric potentials) remarkably reduced (4.27%, 5.03% and 8.57% vs 21.64%, P < 0.05). The percentages of ROS-positive sperm in the pre-capacitation, capacitated, control and Pg-induced groups were 2.89%, 0.70%, 4.25% and 1.90%, respectively, significantly lower in the capacitated than in the pre-capacitation group (P < 0.01), but dramatically increased in the control group after another hour of swim-up incubation and markedly higher than in the Pg-induced group (P < 0.01)., Conclusion: Progesterone induction can hyperactive human sperm motility, inhibit the relative activity of mitochondria, keep mitochondria potential at a more balanced level, and reduce the production of ROS, which may help to raise the rate of in vitro fertilization and improve the quality of embryos.

Recently, the literature has emphasized the aims and logistics of public engagement, rather than its epistemic and cultural processes. In this conceptual article, we use our work on surgical simulation to describe a process that has moved from the classroom and the research laboratory into the public sphere. We propose an innovative shared immersion model for framing the relationship between engagement activities and research. Our model thus frames the public engagement experience as a participative encounter, which brings visitor and researcher together in a shared (surgical) experience mediated by experts from a range of domains.

Five new derivatives (2-6) were semi-synthesized using compound 1, a dihydro-β-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 2-6 were confirmed by 1D- and 2D-NMR and HR-ESI-MS spectra. In addition, antifeedant activities of these compounds (1-6) were tested against the 3rd-instar larvae of Mythimna separata. Antifeedant effects of compounds 2 and 4 were greater than the parent compound 1 whereas other compounds exhibited low to no feeding deterrent effects against third instar M. separata larvae in lab bioassays. Therefore, our results suggest that acylated and reduced derivatives at C-8 and C-2, respectively, of 1 may improve the antifeeding effect. This preliminary information will be useful in designing new insect control agents against M. separata and other important pests.

A series of novel derivatives of 21E-benzylidene-pregn-1,4-diene-3,20-dione 7a-g and 21E-benzylidene-4-chloro-pregn-1,4-diene-3,20-dione 8a-g was synthesized from the commercially available progesterone. These title compounds were evaluated for their cytotoxic activity against brine shrimp (Artemia salina) and murine Lewis lung carcinoma cells (LLC). It was found that compounds 7a-g exhibited stronger activities than 8a-g against the brine shrimps, and some of the tested compounds possessed weak inhibition of LLC cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: There is limited research on teachers' psychosocial work environment and mental health, and most has been conducted in predominantly Western countries that share a number of important common characteristics that distinguish them from countries in many other regions of the world. Within the framework of the effort-reward imbalance (ERI) theoretical model, the relationship between the psychosocial work environment and mental health of teachers in the United Kingdom (UK) and Hong Kong (HK) was investigated., Methods: Full-time qualified teachers from both the UK and HK (N = 259) participated in the research. They were asked to fill in a set of questionnaires that measured their perceived stress, mental health, psychosocial work environment and demographic information., Results: Perceived stress was found to predict teachers' mental health. Overcommitment, the intrinsic component of the ERI model, predicted mental health among HK teachers. There were significant differences in the psychosocial variables between UK and HK teachers., Conclusion: The results showed support for the ERI model and in particular for the relationship between stress and mental health and demonstrated the role of overcommitment in the teaching profession. Some implications are discussed for combating cultural differences in managing the psychosocial work environment of teachers.

A series of 35 benzimidazole derivatives were synthesized from 2-chloromethyl-1H-benzimidazole in good yields. Their structures were characterized by (1)H and (13)C NMR and HRESIMS. Antifungal activities of all of the synthesized compounds were evaluated against five phytopathogens fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) using the mycelium growth rate method. Compound 4m displayed strong growth inhibition of C. gloeosporioides, A. solani, and F. solani with IC50 of 20.76, 27.58, and 18.60 μg/mL, respectively. Selective inhibition of B. cinerea instead of the other fungal pathogenes was observed with 7f (IC50 of 13.36 μg/mL), comparable to that of positive control, a commercial agricultural fungicide hymexazol (IC50 of 8.92 μg/mL). Compound 5b exhibited remarkable antifungal properties against Cytospora sp., C. gloeosporioides, B. cinerea, and F. solani with IC50 values of 30.97, 11.38, 57.71, and 40.15 μg/mL, respectively; among the target fungi, 5b was the most active compound and superior to the reference against C. gloeosporioides alone. Structure-activity relationship (SAR) data of these compounds are as follows: (1) introduction of the chlorine atom on para-position in the benzene ring help to increase activity (4f vs 4c; 7f vs 7n), (2) the sulfonyl group is critical for the inhibition of C. gloeosporioides (5b and 5c vs 5a), and (3) the unsubstituted benzene ring improve activity (4m vs 4n, 4e and 4a). Thus, compounds 5b, 4m, and 7f emerged as a new leading structure for the development of new fungicides.

In order to explore the genotype distribution and molecular evolution of non-polio enterovirus (NPEVs)in Yunnan Province,the People's Republic of China, we sequenced and analyzed the partial VP1 coding region of 105 NPEVs isolated from acute flaccid paralysis (AFP) surveillance in Yunnan province during a 5- year study period from 2006 to 2010. The viral genomes of 105 NPEVs were translated to corresponding amino acid sequences and compared with those of the prototype strains, and the phylogenetic tree was constructed among these VP1 nucleotide sequences and other prototype strains from GenBank. Analysis showed that 18 isolates were classified into 7 serotypes of human enterovirus A species, while 77 isolates into 22 serotypes of B and 10 isolates into 4 serotypes of C species. However, we did not isolate any viruses which belonged to human enterovirus D species. Thus, under AFP surveillance, human enterovirus B species accounted for 73. 3% of the 105 isolates and was considered as the predominant one,followed by human enterovirus A(17. 1%) and human enterovirus C(9. 5%). Phylogenetic analysis showed that various serotypes of the virus and the corresponding prototype strains or other representative strains clustered into the same grooup, however, Yunnan strains and prototype strains were located in the different branches (except CA2,EV90 and EV76). The degree of variation was different even among the same genotype strains. This report showed that different genotype strains spread widely in Yunnan Province.

Objective: To study the correlation between isoeitratedehydrogenasel 1 (IDH1) mutation and prognosis in supratentorial high-grade astrocytomas., Methods: There were 217 samples of supratentorial high-grade astrocytomas specimens collected for DNA extraction, IDH1 mutation of each patient was determined by PCR and direct sequencing. The differences of clinical features were compared between mutant group and wild type group. The relationship between IDH1 mutation and overall survival of the patients was studied with Kaplan-Meier survival curve, while multiple factors analysis was carried out by COX regression model., Results: There were 43 (19.3%) IDH1 mutations in 217 specimens, of which 9 (24.3%) in WHO grade III, 34 (18.9%) in WHO grade IV. The mean age of primary glioblastoma multiforme (GBM) in mutant type group and wild type group were 39.17 and 47.66 years old respectively (P < 0.05). The median survival time was 64 weeks for the patients in IDH1 mutation group and 50 weeks for those in wild type group, and the difference was statistically significant (P < 0.001). The median survival time was 51 weeks for the wild type group of WHO grade III cases and 58 weeks for the mutant group of WHO grade IV cases (P < 0.001). COX multiple variable analysis showed that IDH1 mutation, surgical resection, preoperative Karnofsky performance, radiotherapy and chemotherapy were statistically significant in prognosis (P < 0.05)., Conclusion: IDH1 mutation can be found in supratentorial high-grade astrocytomas, the patients with IDH1 mutation may have a better prognosis.

Objective: To examine the association between postconcussive symptoms and mild traumatic brain injury (MTBI) among combat veterans while adjusting for posttraumatic stress disorder (PTSD) and depression., Patients: Military personnel with provider-diagnosed MTBI (n = 334) or nonhead injury (n = 658) were identified from the Expeditionary Medical Encounter Database., Main Outcome Measures: Post-Deployment Health Assessments and Re-Assessments were used to examine postconcussive symptoms and self-rated health., Results: Personnel with MTBI were more likely to report headache (odds ratio [OR] = 3.37; 95% confidence interval [CI] = 2.19-5.17), back pain (OR = 1.79; 95% CI = 1.23-2.60), memory problems (OR = 1.86; 95% CI = 1.20-2.88), tinnitus (OR = 1.63; 95% CI = 1.10-2.41), and dizziness (OR = 2.13; 95% CI = 1.06-4.29) compared with those with non-head injuries. Among those with MTBI, self-reported decline in health was associated with memory problems (OR = 5.07; 95% CI = 2.56-10.02) and dizziness (OR = 10.60; 95% CI = 3.48-32.27)., Conclusions: Mild traumatic brain injury is associated with reports of negative health consequences among combat veterans even when accounting for co-occurring psychological morbidity. The identification of postconcussive symptoms related to declines in a service member's self-rated health may be important in targeting and prioritizing clinical interventions.

Background: Zinc finger, DHHC-type containing 2 (ZDHHC2), originally named as reduced expression associated with metastasis protein (REAM), has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma., Methodology/principal Findings: Quantitative Real-Time PCR (qRT-PCR) and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472) of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001) and histological grade (p<0.001). Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001)., Conclusions/significance: Our data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.

Background: The present study was aimed to investigate the protective effects of different-time-ischemic preconditioning on the reperfusion injury in fatty livers in rats, and to elucidate the mechanisms underlying the protective effects and the optimal safe ischemic preconditioning time on the hepatic IR injury in steatotic livers., Methodology/principal Findings: A rat fatty liver model was established by high-fat diet feeding. We investigated the changes in the concentration of AST, ALT, LDH and NO in the serum, and of MDA, SOD, and MPO in the liver samples in response to different ischemic preconditioning times and ischemia-reperfusion injury. Histological analysis was performed to evaluate the results of the hepatic fatty infiltration. 1) At 24 h after 15 min ischemic preconditioning with 10 min reperfusion (15 min +10 min IP), the extent and area of the necrosis was markedly higher in the fatty liver samples with respect to IR, compared to the normal liver samples. 2) In response to the treatment of 5/8 min +10 min IP, the fatty liver group showed lower levels of serological indicators and liver MDA and MPO compared to the other groups, while the SOD activity of the fatty liver group was significantly higher than the other groups (p<0.05). Compared to the corresponding IR group, all IP groups showed a significantly higher serum NO concentration (p<0.05). Among the fatty liver groups, the 5/8 min+10 min IP group showed the highest NO concentration (p<0.05)., Conclusions/significance: Fat infiltration could aggravate the ischemia-reperfusion injury in the rat liver. Furthermore, ischemic preconditioning could increase the tolerance of the fatty liver, which was induced by the high-fat diet, to hepatic ischemia-reperfusion injury in rats. The protocol of 5/8 min +10 min IP was the optimal regimen for the treatment of moderate and severe fatty livers.

Objective: To investigate the relationship between isocitrate dehydrogenase 1 (IDH1) mutation and clinicopathological features in human supratentorial WHO grade II gliomas., Methods: Ninety five supratentorial WHO grade II glioma patients were treated in our department from January 2009 to January 2011. The clinical data and tumor samples of each patient were collected. IDH1 mutation in the tumor was measured by sequencing the IDH1 gene of tumor specimen. The relationship between IDH1 mutation and the clinicopathological features was analyzed., Results: There were 69 cases (72.6%) with IDH1 mutations were found, all of which were R132H type mutations. The mutation rates of diffuse astrocytoma, oligodendroglioma and oligoastrocytoma were 73.6%, 68.8% and 73.1% respectively. The mean ages of IDH1 mutant group and wild type group were significantly different [(39 6 +/- 7.4) yr. vs. (46.9 +/- 11.6) yr., P < 0.05). The mutant rates of patients aged > or = 50 years and < 50 years were 43.8% and 78.5% respectively (P < 0.05), while those of male patients and female patients were 68.6% and 77.3% respectively (P > 0.05). The mutant rates of patients whose tumor > or = 5 cm and < 5 cm were 60.0% and 90.0% respectively (P < 0.05), while those of monolobe involvement group and deepen structures involvement group were 93.3% and 32.0% respectively (P < 0.05)., Conclusion: The mutation of IDH1 in supratentorial WHO grade II glioma is common, and is associated with patients' age, tumor size and tumor location.

The reactions of resveratrol with proinflammatory oxidants including hypochlorous and hypobromous acids in phosphate-buffered saline/methanol solution were carried out and eight halogenated resveratrol derivatives differing in the number and position of halogen atoms, and the configuration of double bond were obtained. Halogenation of resveratrol took place only at the aromatic A ring, and interestingly, the halogenation increased antioxidant activity of this parent molecule in the 2,2'-azobis(2-amidinopropane) hydrochloride-induced RBC haemolysis model. Additionally, antimicrobial activity of the derivatives against Gram-positive bacteria, Gram-negative bacteria and fungi were tested, and toward Candida albicans, 2-chloro-resveratrol and 2-bromo-resveratrol were more active than the unmodified form and the reference compound fluconazole., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aims: Hydrogen sulfide (H(2)S), a novel gaseous mediator, has been recognized to protect neurons from overexcitation by enhancing the activity of the adenosine triphosphate-sensitive potassium (K-ATP) channel. However, no direct evidence supports that the K-ATP channel contributes to the neuroprotective effect of H(2)S in neurodegeneration. Herein, wild-type and Kir6.2 knockout (Kir6.2(-/-)) mice were used to establish the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD) so as to investigate the involvement of K-ATP channels in the neuroprotection of H(2)S., Results: Systemic administration of sodium hydrosulfide (NaHS) (an H(2)S donor, 5.6 mg/kg/day) for 7 days rescued MPTP-induced loss of dopaminergic (DA) neurons in substantia nigra compacta of both Kir6.2(+/+) and Kir6.2(-/-) mice. Consistently, NaHS (100 μM) protected primary mesencephalic neurons against 1-methyl-4-phenylpyridinium (MPP(+))-induced cytotoxicity in both genotypes. We further found that deficiency of mitochondrial uncoupling protein 2 (UCP2), which reduces reactive oxygen species (ROS) production and functions as upstream to the K-ATP channel in determining vulnerability of DA neurons, abolished the protective effects of H(2)S against either DA neuron degeneration in the PD mouse model or MPP(+)-induced injury in primary mesencephalic neurons. Rationally, UCP2 evokes mild uncoupling, which in turn diminishes ROS accumulation in DA neurons. Furthermore, H(2)S exerted neuroprotective effect via enhancing UCP2-mediated antioxidation and subsequently suppressing ROS-triggered endoplasmic reticulum stress as well as ultimately inhibiting caspase 12-induced neuronal apoptosis., Innovation and Conclusion: H(2)S protects DA neurons against degeneration in a UCP2 rather than Kir6.2/K-ATP channel-dependent mechanism, which will give us an insight into the potential of H(2)S in terms of opening up new therapeutic avenues for PD.

gp78 is a membrane-anchored ubiquitin ligase mediating the degradation of HMG-CoA reductase (HMGCR) and Insig-1. As a rate-limiting enzyme in cholesterol biosynthesis, HMGCR undergoes rapid sterol-promoted degradation. In contrast, destruction of Insig-1 releases its inhibition on SREBP and stimulates the expression of lipogenic genes. Thus, gp78 has opposite effects on lipid biosynthesis. We here generated liver-specific gp78 knockout (L-gp78(-/-)) mice and showed that although the degradation of HMGCR was blunted, SREBP was suppressed due to the elevation of Insig-1/-2, and therefore the lipid biosynthesis was decreased. The L-gp78(-/-) mice were protected from diet-/age-induced obesity and glucose intolerance. The livers of L-gp78(-/-) mice produced more FGF21, which activated thermogenesis in brown adipocytes and enhanced energy expenditure. Together, the major function of gp78 in liver is regulating lipid biosynthesis through SREBP pathway. Ablation of gp78 decreases the lipid levels and increases FGF21, and is beneficial to patients with metabolic diseases.

Background: Sporotrichosis is a subcutaneous fungal infection caused by a thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from traumatic inoculation or contact with animals. Most cases were reported mainly in the tropics and subtropics., Objective:   The objective of our study is to assess the clinical characteristic of cutaneous sporotrichosis among our patients., Methodology: We performed a retrospective review of all cases diagnosed with cutaneous sporotrichosis from July 2004 to June 2010. Patients' medical records were retrieved and analyzed according to demography, preceding trauma, sites of lesions, clinical subtypes, treatment, and clinical response., Results: Nineteen cases were diagnosed with cutaneous sporotrichosis with a male/female ratio of 9:10. Thirteen cases (68.4%) were able to recall preceding trauma, and seven of them reported cat scratches or cat bites. Lymphocutaneous sporotrichosis was observed in 13 cases (68.4%) followed by four cases of fixed cutaneous sporotrichosis and two cases of disseminated sporotrichosis. Histologically, 11 cases (57.8%) demonstrated a granulomatous reaction. Sporothrix schenckii was cultured in 12 cases (63.2%). Thirteen cases (68.4%) were successfully treated with oral itraconazole alone for a mean duration of 15.6 weeks. Two cases with disseminated cutaneous sporotrichosis were treated with intravenous amphotericin B., Conclusion:   Lymphocutaneous sporotrichosis was the most common subtype of cutaneous sporotrichosis in our series, with cat scratches or bites being the most common preceding trauma. Oral itraconazole was highly effective for the localized subtypes, whereas intravenous amphotericin B was required in disseminated cutaneous sporotrichosis., (© 2012 The International Society of Dermatology.)

Disseminated sporotrichosis is uncommon and usually occurs in patients who are immunodeficient. Here we describe a male patient who was otherwise in good physical condition, who presented with disseminated sporotrichosis. The only significant event in his past medical history was lepromatous leprosy which had been treated 42 years earlier.

A novel cyathane diterpenoid, designated scabronine M (1), was isolated from the fruiting bodies of the mushroom Sarcodon scabrosus together with 10 known compounds. The structure of the new compound was elucidated on the basis of extensive spectroscopic analysis including 2D-NMR. Among these compounds, only scabronine M (1) significantly inhibited dose-dependently NGF-induced neurite outgrowth in PC12 cells without cytotoxicity, possibly through suppressing the phosphorylation of the receptor Trk A and the extracellular signal regulated kinases (ERK). This is the first report of novel neurite outgrowth-inhibiting activity in PC12 cells of this group of diterpenoids., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Bikunin is a proteoglycan exhibiting broad-spectrum inhibitory activity against serine proteases and could potentially suppress tumor cell invasion and metastasis. Here, we have successfully expressed recombinant human bikunin (rh-bikunin) in Pichia pastoris and also established the purification procedure. Different fusion genes of h-UTI and domain I, domain I and domain II, domain I, domain II and domain III of human serum albumin (HSA) were inserted into expression vector pPICZαA. After expressed in shake flask, rh-bikunin was produced in an 30-L fermenter and purified by affinity chromatography and cation exchange chromatography. The final expression levels were 200 mg/L and we got totally 1.08 g (3650 IU/mg) of active purified rh-bikunin (purity is 98%) from 20 L of fermentation broth. The rh-bikunin consists of unique form with molecular masses of 25 kDa, and has the same N-terminals sequence as human native bikunin. This study provided a new method for high level expression of active rh-bikunin by using HSA as fusion parter.

The aim of the present study was to assess the influences of PRKCH gene variants (1425G/A and &#95;15) on the risk of coronary artery disease (CAD) in a Chinese population. Our study population consisted of 470 CAD patients and 434 control subjects. The alleles frequencies of the two variants were significantly higher among CAD patients than control subjects (P = 0.001 for 1425G/A and P = 0.001 for &#95;15, respectively). In the CAD group, the A allele carriers of 1425G/A and &#95;15 polymorphisms had higher low-density lipoprotein cholesterol (LDL-C) levels than homozygote G allele carriers (P = 0.001 and P = 0.021, respectively). In a multiple logistic regression model adjusted for age, sex, body mass index (BMI), etc., a markedly increased risk of developing CAD was found in subjects carrying GA or AA genotype (P = 0.005 and P = 0.018, respectively). In conclusion, we observed that there was a remarkable association of minor alleles (1425G/A and &#95;15) in the PRKCH gene with an elevated risk of CAD and increased levels of LDL-C in this Chinese population.

Objectives: It is widely acknowledged that teachers are suffering from work-related health problems. However, the implementation of relevant occupational safety and health (OSH) policies is complex and under-studied. This study reviews key legislation of relevance to psychosocial health and explores stakeholders' perceptions on their implementation in Hong Kong (HK) schools., Methods: The content of OSH legislation applicable to psychosocial health was systematically reviewed by the modified WHO checklist on legislation. Semi-structured interviews were then conducted with 38 key stakeholders. These were transcribed and subjected to Framework Analysis., Results: The review showed that there were several ambiguities in the legislation and the interviews found that awareness and understanding in relation to OSH issues and policies differed on the basis of the level of implementation bodies. The importance of management, trust, communication and interpersonal relationships was emphasised., Conclusion: On the basis of the study it is concluded that implementation of psychosocial health policies in HK schools is poor and there appears to be a gap among stakeholder communication. Also, the content of these policies needs to be clarified so that it can be more conducive to implementation in practice. The improvement of OSH climate and social capital could foster a more effective implementation of OSH policies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Based on the observed biological activities of coumarins and resveratrol, we synthesized fourteen hydroxylated 3-phenylcoumarins (stilbene-coumarin hybrids) including six novel ortho-hydroxy-methoxy substituted derivatives, 1-14, by Perkin reaction. We characterized these compounds concerning their antioxidant activity against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced pBR322 DNA strand breakage, and their antiproliferative effects on human promyelocytic leukemia HL-60 and human lung adenocarcinoma epithelial A549 cells. Structure-activity relationship information suggests that the introduction of ortho-hydroxy-methoxy groups and ortho-dihydroxy groups on the aromatic A ring could efficiently improve antiproliferative activity. Interestingly, a new derivative, 6-methoxy-7-hydroxy-3-(4'-hydroxyphenyl)coumarin, 9, behaved as a poor antioxidant but appeared to be the most potent antiproliferative agent among the compounds examined, and this activity was mediated by deregulation in cell cycle and induction of apoptosis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)