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1.  Highly Selective Domino Multi-Cyclizations for Forming Polycyclic Fused Acridines and Azaheterocyclic Skeletons 
Organic letters  2013;15(7):1540-1543.
Highly selective four-component domino multi-cyclizations for the synthesis of new fused acridines and azaheterocyclic skeletons have been established by mixing common reactants in isobutyric acid under microwave irradiation. The reactions proceeded at fast rates, and were conducted to completion within 20–30 min. Up to seven new chemical bonds, four rings and four stereocenters were assembled in a convenient one-pot operation. The resulting hexacyclic and pentacyclic fused acridines and their stereochemistry have been fully characterized and determined by X-ray structural analysis.
doi:10.1021/ol400322v
PMCID: PMC3635953  PMID: 23506186
2.  Intramolecular Anodic Olefin Coupling Reactions and the Synthesis of Cyclic Amines 
Anodic olefin coupling reactions using a tosylamine trapping group have been studied. The cyclizations are favored by the use of a less-polar radical cation and more basic reaction conditions. The most significant factor for obtaining good yields of cyclic product is the use of the more basic reaction conditions. However, a number of factors including the nature of both the solvent and the electrolyte used can influence the yield of the cyclizations. The cyclizations allow for the rapid synthesis of both substituted proline and pipecolic acid type derivatives.
doi:10.1021/ja910586v
PMCID: PMC3950632  PMID: 20131795
3.  Intramolecular Anodic Olefin Coupling Reactions: Using Competition Studies to Probe the Mechanism of Oxidative Cyclization Reactions 
Organic letters  2010;12(8):1720-1723.
A competition experiment was designed so that the relative rates of anodic cyclization reactions under various electrolysis conditions can be determined. Reactions with ketene dithioacetal and enol ether-based substrates that use lithium methoxide as a base were shown to proceed through radical cation intermediates that were trapped by a sulfonamide anion. Results for the oxidative coupling of a vinyl sulfide with a sulfonamide anion using the same conditions were consistent with the reaction proceeding through a nitrogen-radical.
doi:10.1021/ol100317t
PMCID: PMC3943423  PMID: 20302359
4.  Intramolecular Hydroamination of Dithioketene Acetals: An Easy Route To Cyclic Amino Acid Derivatives 
Organic letters  2010;12(22):5174-5177.
Catalytic intramolecular hydroamination of dithioketene acetals was developed for the synthesis of cyclic amino acid derivatives. Triggered by the addition of a catalytical amount of n-BuLi, the reaction proceeds to give proline and pipecolic acid derivatives in excellent yields and diastereoselectivity.
doi:10.1021/ol102193x
PMCID: PMC3943425  PMID: 20945849
5.  Increased Risk for Developing Major Adverse Cardiovascular Events in Stented Chinese Patients Treated with Dual Antiplatelet Therapy after Concomitant Use of the Proton Pump Inhibitor 
PLoS ONE  2014;9(1):e84985.
Background
Some clinical studies have demonstrated that the proton pump inhibitor (PPI) could decrease clopidogrel platelet response and increase major adverse cardiovascular events (MACE) in white or black subjects. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be an increased risk for developing MACE after concomitant use of dual antiplatelet therapy (DAT) and a PPI in Chinese patients treated with percutaneous coronary intervention (PCI) and stenting.
Methods
This study was a 5-year, single-center, retrospective cohort analysis of eligible patients (n = 6188) who received DAT and a PPI concomitantly (defined as PPI users) before discharge and/or 12-month follow-up after discharge as compared with those who received DAT alone (also defined as non-PPI users, n = 1465). The incidence of recurrent MACE, such as myocardial infarction (MI), definite stent thromboses (ST), or cardiovascular death, was compared between the PPI users and non-users.
Results
PPI users had a significantly higher incidence of the MACE than non-users (13.9% vs. 10.6%; adjusted HR: 1.33; 95% CI: 1.12 – 1.57, P = 0.007). Stratified analysis revealed that concurrent use of DAT and a PPI was associated with a significantly increased risk for developing ST compared with DAT alone (1% vs. 0.4%; adjusted HR: 2.66, 95% CI: 1.16 – 5.87, P = 0.012). However, there were no significant differences in the risk of MI, cardiovascular death and other adverse events, regardless of combination of clopidogrel and a PPI.
Conclusions
The study further suggests that concomitant use of DAT and a PPI may be associated with an increased risk for developing MACE, in particular definite ST, in Chinese PCI patients after discharge as compared with use of DAT alone.
doi:10.1371/journal.pone.0084985
PMCID: PMC3885647  PMID: 24416326
6.  Effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients undergone esophagectomy 
Object: Sevoflurane and propofol are both widely used in clinical anesthesia. The aim of this study is to compare the effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients receiving esophagectomy. Methods: Forty adult patients undergoing an elective open-chest thoracotomy for esophagectomy were randomized to receive either propofol (n=20) or sevoflurane (n=20) as the main anesthetic agent. The study was performed in Changzheng Hospital. Hemodynamic data were recorded at specific intervals: before the surgery (T0), BIS values reaching 40 after anesthesia induction (T1), two-lung ventilation (T2), ten minutes after one-lung ventilation (T3), the end of the operation (T4) using PiCCO2 and Swan-Ganz catheter. Results: CI, RVEF, RVSWI and RVEDVI were significantly smaller in propofol group than those in sevoflurane group throughout the surgery (P<0.05). However, SVRI was significantly greater in propofol group than that in sevoflurane group (P<0.05). Compared with the patients in propofol group, the patients who received sevoflurane had a greater reduction in OI and increase in Os/Ot (P<0.05). And, PVRI was significantly smaller in sevoflurane group than in propofol group (P<0.05). Conclusion: Anesthesia with sevoflurane preserved better right ventricular function than propofol in patients receiving esophagectomy. However, propofol improved oxygenation and shunt fraction during one-lung ventilation compared with sevoflurane anesthesia. To have the best effect, anesthesiologists can choose the two anesthetics flexibly according to the monitoring results.
PMCID: PMC3885482  PMID: 24427348
Sevoflurane; propofol; right ventricular function; pulmonary circulation; esophagectomy
7.  Competitive Interactions between Parasitoids Provide New Insight into Host Suppression 
PLoS ONE  2013;8(11):e82003.
Understanding the dynamics of potential inter- and intraspecific competition in parasitoid communities is crucial in the screening of efficient parasitoid species and for utilization of the best parasitoid species combinations. In this respect, the host-parasitoid systems, Bemisia tabaci and two parasitoids, Eretmocerus hayati (exotic) and Encarsia sophia (existing) were studied under laboratory conditions to investigate whether interference competition between the exotic and existing species occurs as well as the influence of potential interference competition on the suppression of the host B. tabaci. Studies on interspecific-, intraspecific- and self-interference competition in two parasitoid species were conducted under both rich and limited host resource conditions. Results showed that (1) both parasitoid species negatively affect the progeny production of the other under both rich and limited host resource conditions; (2) both parasitoid species interfered intraspecifically on conspecific parasitized hosts when the available hosts are scarce and; 3) the mortality of B. tabaci induced by parasitoids via parasitism, host-feeding or both parasitism and host-feeding together varied among treatments under different host resource conditions, but showed promise for optimizing control strategies. As a result of our current findings, we suggest a need to investigate the interactions between the two parasitoids on continuous generations.
doi:10.1371/journal.pone.0082003
PMCID: PMC3842984  PMID: 24312394
8.  Characteristics of Clinical Shiga Toxin-Producing Escherichia coli Isolated from British Columbia 
BioMed Research International  2013;2013:878956.
Shiga toxin-producing Escherichia coli (STEC) are significant public health threats. Although STEC O157 are recognized foodborne pathogens, non-O157 STEC are also important causes of human disease. We characterized 10 O157:H7 and 15 non-O157 clinical STEC derived from British Columbia (BC). Eae, hlyA, and stx were more frequently observed in STEC O157, and 80 and 100% of isolates possessed stx1 and stx2, respectively. In contrast, stx1 and stx2 occurred in 80 and 40% of non-O157 STEC, respectively. Comparative genomic fingerprinting (CGF) revealed three distinct clusters (C). STEC O157 was identified as lineage I (LI; LSPA-6 111111) and clustered as a single group (C1). The cdi gene previously observed only in LII was seen in two LI O157 isolates. CGF C2 strains consisted of diverse non-O157 STEC while C3 included only O103:H25, O118, and O165 serogroup isolates. With the exception of O121 and O165 isolates which were similar in virulence gene complement to STEC O157, C1 O157 STEC produced more Stx2 than non-O157 STEC. Antimicrobial resistance (AMR) screening revealed resistance or reduced sensitivity in all strains, with higher levels occurring in non-O157 STEC. One STEC O157 isolate possessed a mobile blaCMY-2 gene transferrable across genre via conjugation.
doi:10.1155/2013/878956
PMCID: PMC3807556  PMID: 24199201
9.  A video-assisted thoracic surgical lobectomy for a lung tumour with a rare anomalous pulmonary artery 
A detailed knowledge of anomalies of the anatomical course of the pulmonary vessels is extremely important for video-assisted thoracic surgery (VATS). Inadvertent vascular ligation and dissection are catastrophic for patients undergoing lobectomy. We describe a case with a rare anomaly of the left pulmonary artery and highlight the importance of identifying the courses of pulmonary vessels for VATS lobectomy.
doi:10.1093/icvts/ivs290
PMCID: PMC3445375  PMID: 22815327
Video-assisted thoracic surgery; Anomaly; Pulmonary artery
10.  Phytoestrogen α-Zearalanol Attenuates Homocysteine-Induced Apoptosis in Human Umbilical Vein Endothelial Cells 
BioMed Research International  2013;2013:813450.
Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. The enhanced nitrative stress plays an important role in homocysteine-induced endothelial dysfunction. Previous studies have showed that phytoestrogen α-zearalanol alleviated endothelial injury in ovariectomized hyperhomocysteinemic rats; however, the underlying mechanism remains to be clarified. This study was to investigate the effects of α-zearalanol on homocysteine-induced endothelial apoptosis in vitro and explore the possible role of nitrative stress in these effects. Results showed that homocysteine (500 μmol/L, 24 h) induced the apoptosis of human umbilical vein endothelial cells (HUVECs) obviously, and this effect was significantly attenuated by pretreatment with α-zearalanol (10−8~10−6 mol/L). Moreover, α-zearalanol downregulated proapoptotic protein Bax, upregulated antiapoptotic proteins Bcl-2 and Bcl-XL, and decreased the expression and activity of caspase-9. These findings demonstrated that α-zearalanol could effectively alleviate homocysteine-induced endothelial apoptosis, and this antiapoptosis effect might be related to the inhibition of the intrinsic pathway. Western blot indicated an enhanced 3-nitrotyrosine expression in HUVECs when challenged with homocysteine, which was attenuated by pretreatment with α-zearalanol. This result implied that inhibition of nitrative stress might play a role in the protective effect of α-zearalanol on endothelial cells. Such discovery may shed a novel light on the antiatherogenic activities of α-zearalanol in hyperhomocysteinemia.
doi:10.1155/2013/813450
PMCID: PMC3806352  PMID: 24195080
11.  Solubilization and Stabilization of Isolated Photosystem I Complex with Lipopeptide Detergents 
PLoS ONE  2013;8(9):e76256.
It is difficult to maintain a target membrane protein in a soluble and functional form in aqueous solution without biological membranes. Use of surfactants can improve solubility, but it remains challenging to identify adequate surfactants that can improve solubility without damaging their native structures and biological functions. Here we report the use of a new class of lipopeptides to solubilize photosystem I (PS-I), a well known membrane protein complex. Changes in the molecular structure of these surfactants affected their amphiphilicity and the goal of this work was to exploit a delicate balance between detergency and biomimetic performance in PS-I solubilization via their binding capacity. Meanwhile, the effects of these surfactants on the thermal and structural stability and functionality of PS-I in aqueous solution were investigated by circular dichroism, fluorescence spectroscopy, SDS-PAGE analysis and O2 uptake measurements, respectively. Our studies showed that the solubility of PS-I depended on both the polarity and charge in the hydrophilic head of the lipopeptides and the length of its hydrophobic tail. The best performing lipopeptides in favour of PS-I solubility turned out to be C14DK and C16DK, which were comparable to the optimal amphiphilicity of the conventional chemical surfactants tested. Lipopeptides showed obvious advantages in enhancing PS-I thermostability over sugar surfactant DDM and some full peptide amphiphiles reported previously. Fluorescence spectroscopy along with SDS-PAGE analysis demonstrated that lipopeptides did not undermine the polypeptide composition and conformation of PS-I after solubilization; instead they showed better performance in improving the structural stability and integrity of this multi-subunit membrane protein than conventional detergents. Furthermore, O2 uptake measurements indicated that PS-I solubilized with lipopeptides maintained its functionality. The underlying mechanism for the favorable actions of lipopeptide in PS-I solubilization and stabilization is discussed.
doi:10.1371/journal.pone.0076256
PMCID: PMC3787008  PMID: 24098786
12.  Short peptide-directed synthesis of one-dimensional platinum nanostructures with controllable morphologies 
Scientific Reports  2013;3:2565.
Although one dimensional (1D) Pt nanostructures with well-defined sizes and shapes have fascinating physiochemical properties, their preparation remains a great challenge. Here we report an easy and novel synthesis of 1D Pt nanostructures with controllable morphologies, through the combination of designer self-assembling I3K and phage-displayed P7A peptides. The nanofibrils formed via I3K self-assembly acted as template. Pt precursors ((PtCl4)2− and (PtCl6)2−) were immobilized by electrostatic interaction on the positively charged template surface and subsequent reduction led to the formation of 1D Pt nanostructures. P7A was applied to tune the continuity of the Pt nanostructures. Here, the electrostatic repulsion between the deprotonated C-terminal carboxyl groups of P7A molecules was demonstrated to play a key role. We finally showed that continuous and ordered 1D Pt morphology had a significantly improved electrochemical performance for the hydrogen and methanol electro-oxidation in comparison with either 1D discrete Pt nanoparticle assemblies or isolated Pt nanoparticles.
doi:10.1038/srep02565
PMCID: PMC3759059  PMID: 23995118
13.  A retrospective study of posterior malleolus fractures 
International Orthopaedics  2012;36(9):1929-1936.
Purpose
In this retrospective study, we evaluated the treatment effect of ankle joint fracture surgery involving the posterior malleolus, and discuss relevant factors influencing the occurrence of traumatic arthritis of the ankle joint.
Methods
A total of 102 cases of ankle joint fractures involving the posterior malleolus in five large-scale skeletal trauma centres in China, from January 2000 to July 2009, were retrospectively analysed in terms of surgical treatment and complete follow-up. Ankle joint mobility, posterior malleolus fragment size, articular surface evenness, Ankle-Hindfoot Scale of the American Orthopedic Foot and Ankle Society (AOFAS) score, and imaging scale score for arthritis were recorded. The degree of fracture pain during rest, active movement, and weight-bearing walking, and satisfaction with treatment were evaluated using a visual analogue scale (VAS).
Results
The average AOFAS score was 95.9, excellence rate was 92.2 %, and average VAS scores for degree of fracture pain during rest, active movement, and weight-bearing walking were 0.15, 0.31, and 0.68, respectively. Thirty-six cases showed arthritic manifestations. Ankle joint mobility along all directions on the injured side was lower than that on the unaffected side. There was no obvious difference in treatment effect between the fixed and unfixed posterior malleolus fragment groups for all and for fragment size of <25 %; between fixing the posterior malleolus fragment from front to back or from back to front; or between elderly patients (≥60 years old) and young patients (<60 years old). There was a distinct difference in the treatment effect between articular surface evenness and unevenness for all and for fragment size of ≥25 %.
Conclusions
For all 102 cases of ankle joint fracture involving the posterior malleolus, the treatment effect was satisfactory. Restoration of an even articular surface, especially when fragment size ≥25 %, should be attempted during treatment.
doi:10.1007/s00264-012-1591-9
PMCID: PMC3427438  PMID: 22777382
14.  Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones 
Summary
Carboxylic acids have been electro-oxidatively coupled to electron-rich olefins to form lactones. Kolbe decarboxylation does not appear to be a significant competing pathway. Experimental results indicate that oxidation occurs at the olefin and that the reaction proceeds through a radical cation intermediate.
doi:10.3762/bjoc.9.186
PMCID: PMC3778411  PMID: 24062822
carboxylic acid; cyclization; electrolysis; free radical; kolbe; radical cation
15.  Application of CRT-D in a Marfan syndrome patient with chronic heart failure accompanied by ventricular tachycardia and ventricular fibrillation 
Marfan syndrome is a systemic connective tissue disease that could affect the cardiovascular system and eventually lead to heart enlargement and heart failure with high mortality, mainly due to progressive heart failure and/or sudden cardiac death caused by malignant arrhythmia. Here we report that a patient received a cardiac resynchronization therapy-defibrillator (CRT-D) with a pre-monitor function for heart failure and experienced obvious improvements in his cardiac function. Postoperative follow-up showed that the patient had reduced morbidity and hospitalization for heart failure, and also experienced improved quality of life.
doi:10.1631/jzus.BQICC710
PMCID: PMC3735978  PMID: 23897797
16.  Surgical outcome of esophageal tuberculosis secondary to mediastinal lymphadenitis in adults: experience from single center in China 
Journal of Thoracic Disease  2013;5(4):498-505.
Objective
Esophageal tuberculosis (ET) is a rare disorder often easily misdiagnosed. The aim of this study is to evaluate the clinical features and to highlight the surgical role in treatment and complication management for undiagnosed ET.
Methods
Between June 2006 and June 2011, six esophageal tuberculosis cases were retrospectively reviewed for their clinical presentations, radiological findings, endoscopic views, surgical treatment and outcome.
Results
The prevalent rate of ET was 0.30%. All patients, aged from 28 to 71 years, presented with dysphagia in six, weight loss in four, and each of retrosternal pain, epigastric pain, fever with cough in one. The duration ranged from two weeks to two months. Involvement of esophagus observed at middle segment in five patients, and at lower segment in one. Endoscopy demonstrated diverticulum with polyps in one patient, ulcer formation in one, and extraneous compression with intact mucosa in four. Five patients underwent video-assisted thoracoscopic surgery (VATS) and one was performed thoracotomy perforation repair for esophagopleural fistula. Diagnoses of all cases were confirmed by histopathological examination and acid-fast bacilli culture. Drug sensitivity test revealed multidrugs resistant mycobacterium tuberculous in one case. All patients discharged and recovered by antituberculous treatment with follow-up time ranged from 12 to 45 months.
Conclusions
ET should be considered as a causative factor for dysphagia. Surgery should be applied in undiagnosed ET. VATS is useful in improving rate of confirmative diagnosis, and relieving symptom of dysphagia. Thoracotomy repair is reserved for complications of ET.
doi:10.3978/j.issn.2072-1439.2013.08.33
PMCID: PMC3755661  PMID: 23991308
Esophageal tuberculosis (ET); dysphagia; video-assisted thoracoscopic surgery (VATS); esophagopleural fistula
17.  Walkable Dual Emissions 
Scientific Reports  2013;3:2199.
Walkable dual emissions, in which the emission bands of the walker reversibly cross or leave those of the stationary ones depending on temperature and concentration, have been demonstrated in cyclic dimeric lanthanide complexes [Ln(hfac)3(PAnPO2)]2 (Ln = EuIII, TbIII; hfac− = hexafluoroacetylacetonate; PAnPO2 = 9,10-bis(diphenylphosphino) anthracene dioxide), providing a concept model for signals exchanging and dispatching. Additionally, good linear relationships are observed between the maximum emission bands of the walker vs the concentrations {lg(M)} and the measurement temperatures (K), implying such materials could be served as potential concentration and temperature sensors.
doi:10.1038/srep02199
PMCID: PMC3712315  PMID: 23857434
18.  Influence of preoperative diastolic dysfunction on hemodynamics and outcomes of patients undergoing orthotopic liver transplantation 
Objective: Left ventricular diastolic dysfunction is receiving more attention in patients with end-stage liver diseases. The importance of diastolic dysfunction observed before orthotopic liver transplantation (OLT) and its adverse effects on hemodynamics and outcomes of OLT patients, have not been fully explored. We carried a retrospective study to investigate the influence of diastolic dysfunction on OLT patients. Methods: Included in this retrospective study were 330 consecutive patients scheduled for cadaveric OLT over a 5-year period. According to preoperative Doppler echocardiogram (ECHO) findings, patients were divided into two groups: DD group (patients with diastolic dysfunction) and control group (patients with normal ECHO). Patient characteristics, operation variables, hemodynamic course, blood products and drug requirements, postoperative courses and outcomes were evaluated. Results: 306 patients met the study entry criteria and 100 had preoperative diastolic dysfunction. Mean artery blood pressure was significantly lower in DD group after graft reperfusion than that in control group (P<0.01). More patients in DD group required epinephrine, and the mean dose of epinephrine was higher in DD group than that in control group (P<0.01). There was no significant difference in postoperative ventilation time, duration of ICU and hospital stay, renal failure and postoperative mortality between the two groups. Conclusion: Diastolic dysfunction is common in liver transplant recipients. Patients with diastolic dysfunction may be associated with substantial hemodynamic alterations after graft reperfusion and need more inotropic support during OLT. Diastolic dysfunction was not associated with significant adverse postoperative outcomes.
PMCID: PMC3664002  PMID: 23724154
Anesthesia; liver transplantation; intraoperative complications; postoperative complications; echocardiography
19.  AhR-Mediated Effects of Dioxin on Neuronal Acetylcholinesterase Expression in Vitro 
Environmental Health Perspectives  2013;121(5):613-618.
Background: Deficits in cognitive functioning have been reported in humans exposed to dioxins and dioxin-like compounds. Evidence suggests that dioxins induce cholinergic dysfunction mediated by hypothyroidism. However, little is known about direct effects of dioxins on the cholinergic system.
Objectives: We investigated the action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on acetylcholinesterase (AChE), a key enzyme in cholinergic neurotransmission.
Methods: We used SK-N-SH human-derived neuronal cells to evaluate the effect of dioxin exposure on AChE.
Results: We consistently found a significant decrease in enzymatic activity of AChE in cultured neurons treated with TCDD. We also found that, unlike organophosphate pesticides that directly act on the catalytic center of AChE, the suppressive effect of dioxin was through transcriptional regulation. The addition of CH223191, an inhibitor of the aryl hydrocarbon receptor (AhR)-dependent pathway, counteracted the TCDD-induced suppression of AChE, suggesting involvement of the AhR-dependent pathway. The existence of putative dioxin-responsive element (DRE) consensus sequences in the human ACHE promoter region further supported this hypothesis. Consistent with the absence of DRE elements in mouse or rat ACHE promoter regions, suppression of AChE by TCDD did not occur in rat neuronal cells, indicating a potential species-specific effect.
Conclusions: In SK-N-SH cells, dioxin suppressed the activity of neuronal AChE via AhR-mediated transcriptional down-regulation. This is the first study to report direct interference by dioxin with the cholinergic neurotransmission system.
doi:10.1289/ehp.1206066
PMCID: PMC3673198  PMID: 23426015
acetylcholinesterase (AChE); aryl hydrocarbon receptor (AhR); dioxin-responsive element (DRE); neuron; 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); transcriptional regulation
20.  Perineuronal nets increase inhibitory GABAergic currents during the critical period in rats 
AIM
To investigate inhibitory γ-aminobutyric acid (GABA) ergic postsynaptic currents (IPSCs) and postsynaptic currents (PSCs) in layer IV of the rat visual cortex during the critical period and when plasticity was extended through dissolution of the perineuronal nets (PNNs).
METHODS
We employed 24 normal Long-Evans rats to study GABAA-PSC characteristics of neurons within layer IV of the visual cortex during development. The animals were divided into six groups of four rats according to ages at recording: PW3 (P21-23d), PW4 (P28-30d), PW5 (P35-37d), PW6 (P42-44d), PW7 (P49-51d), and PW8 (56-58d). An additional 24 chondroitin sulfate proteoglycan (CSPG) degradation rats (also Long-Evans) were generated by making a pattern of injections of chondroitinase ABC (chABC) into the visual cortex 1 week prior to recording at PW3, PW4, PW5, PW6, PW7, and PW8. Immunohistochemistry was used to identify the effect of chABC injection on CSPGs. PSCs were detected with whole-cell patch recordings, and GABAA receptor-mediated IPSCs were pharmacologically isolated.
RESULTS
IPSC peak current showed a strong rise in the age-matched control group, peaked at PW5 and were maintained at a roughly constant value thereafter. Although there was a small increase in peak current for the chABC group with age, the peak currents continued to decrease with the delayed highest value at PW6, resulting in significantly different week-by-week comparison with normal development. IPSC decay time continued to increase until PW7 in the control group, while those in the chABC group were maintained at a stable level after an initial increase at PW4. Compared with normal rats, the decay times recorded in the chABC rats were always shorter, which differed significantly at each age. We did not observe any differences in IPSC properties between the age-matched control and penicillinase (P-ase) group. However, the change in IPSCs after chABC treatment was not reflected in the total PSCs or in basic membrane properties in layer IV of the rat visual cortex.
CONCLUSION
Our results demonstrate that rather than rapidly increasing during the critical period for neuronal plasticity, IPSCs in layer IV of rat visual cortex are maintained at an immature level when PNNs are removed by chABC. This suggests that GABA receptor maturation involves the conformation of the CSPGs in PNNs.
doi:10.3980/j.issn.2222-3959.2013.02.02
PMCID: PMC3633745  PMID: 23638408
gamma-aminobutyric acid receptor; plasticity; visual cortex; development; postsynaptic currents; chondroitinase ABC; chondroitin sulfate proteoglycans; whole-cell patch recording
21.  Ethanol and Methanol Can Improve Huperzine A Production from Endophytic Colletotrichum gloeosporioides ES026 
PLoS ONE  2013;8(4):e61777.
Huperzine A (HupA) is a plant alkaloid that is of great interest as a therapeutic candidate for the treatment of Alzheimer's disease. However, the current production of HupA from plants in large quantity is unsustainable because the plant resource is scarce and the content of HupA in plants is extremely low. Surprisingly, this compound was recently found to be produced by various endophytic fungi, which are much more controllable than the plants due to simpler genetics and ease of manipulation. However, it might be due to the innate properties of endophytic symbiosis, that production of this chemical in large quantity from endophytes has not yet been put into practice. Endophytic Colletotrichum gloeosporioides ES026 was previously isolated from a HupA producing plant and the fungi also proved to produce HupA. In this study, various fermentation conditions were tried to optimize the production of HupA from C. gloeosporioides ES026. Optimization of these parameters resulted in a 25.58% increase in HupA yield. Potato extracts supplemented with glucose or sucrose but not maltose facilitated HupA producing from the fungi. A final concentration of 0.5–2% ethanol stimulated the growth of fungi while methanol with the same treatment slightly inhibited the growth. However, both methanol and ethanol greatly increased the HupA production with the highest yield of HupA (51.89% increment) coming from ethanol treatment. Further analysis showed that both ethanol and methanol were strong inducers of HupA production, while ethanol was partially used as a carbon source during fermentation. It was noticed that the color of that ethanol treated mycelia gradually became dark while methanol treated ones stayed grey during fermentation. The present study sheds light on the importance of optimizing the fermentation process, which, combined with effective inducers, maximizes production of chemicals of important economic interest from endophytic fungi.
doi:10.1371/journal.pone.0061777
PMCID: PMC3629160  PMID: 23613930
22.  Poloxamer 188 Protects Neurons against Ischemia/Reperfusion Injury through Preserving Integrity of Cell Membranes and Blood Brain Barrier 
PLoS ONE  2013;8(4):e61641.
Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to protect against ischemic tissue injury of cardiac muscle, testes and skeletal muscle, but the mechanisms have not been fully understood. In this study, we explored whether P188 had a protective effect against cerebral ischemia/reperfusion injury and its underlying mechanisms. The in vivo results showed that P188 significantly reduced the infarct volume, ameliorated the brain edema and neurological symptoms 24 h after ischemia/reperfusion. In the long-term outcome study, P188 markedly alleviated brain atrophy and motor impairments and increased survival rate in 3 weeks of post stroke period. Additionally, P188 protected cultured hippucampal HT22 cells against oxygen–glucose deprivation and reoxygenation (OGD/R) injury. The ability in membrane sealing was assessed with two fluorescent membrane-impermeant dyes. The results showed that P188 treatment significantly reduced the PI-positive cells following ischemia/reperfusion injury and repaired the HT22 cell membrane rupture induced by Triton X-100. In addition, P188 inhibited ischemia/reperfusion-induced activation of matrix metalloproteinase (MMP)-9 and leakage of Evans blue. Therefore, the present study concludes that P188 can protect against cerebral ischemia/reperfusion injury, and the protection involves multi-mechanisms in addition to the membrane resealing.
doi:10.1371/journal.pone.0061641
PMCID: PMC3628995  PMID: 23613890
23.  Long-term strain improvements accumulate mutations in regulatory elements responsible for hyper-production of cellulolytic enzymes 
Scientific Reports  2013;3:1569.
Long-term strain improvements through repeated mutagenesis and screening have generated a hyper-producer of cellulases and hemicellulases from Penicillium decumbens 114 which was isolated 30 years ago. Here, the genome of the hyper-producer P. decumbens JU-A10-T was sequenced and compared with that of the wild-type strain 114-2. Further, the transcriptomes and secretomes were compared between the strains. Selective hyper-production of cellulases and hemicellulases but not all the secreted proteins was observed in the mutant, making it a more specific producer of lignocellulolytic enzymes. Functional analysis identified that changes in several transcriptional regulatory elements played crucial roles in the cellulase hyper-producing characteristics of the mutant. Additionally, the mutant showed enhanced supply of amino acids and decreased synthesis of secondary metabolites compared with the wild-type. The results clearly point out that we can target gene regulators and promoters with minimal alterations of the genetic content but maximal effects in genetic engineering.
doi:10.1038/srep01569
PMCID: PMC3610096  PMID: 23535838
24.  Correction: Functional Expression of TWEAK and the Receptor Fn14 in Human Malignant Ovarian Tumors: Possible Implication for Ovarian Tumor Intervention 
PLoS ONE  2013;8(3):10.1371/annotation/aa15cad6-0a7a-4b4e-ac1b-b24af35b723c.
doi:10.1371/annotation/aa15cad6-0a7a-4b4e-ac1b-b24af35b723c
PMCID: PMC3600076
25.  Functional Expression of TWEAK and the Receptor Fn14 in Human Malignant Ovarian Tumors: Possible Implication for Ovarian Tumor Intervention 
PLoS ONE  2013;8(3):e57436.
The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in human malignant ovarian tumors, and test TWEAK’s potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC), we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%). Similarly, 35 out of 41 (85.37%) malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients’ clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α), whereas either TWEAK or TNF-α alone didn’t affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1) production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.
doi:10.1371/journal.pone.0057436
PMCID: PMC3587594  PMID: 23469193

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