Optimized aeration strategies for nitrogen removal efficiency: application of end gas recirculation aeration in the fixed bed biofilm reactor.

Aeration strategy played an important role in reactor performance. In this study, when superficial upflow air velocity (SAV) decreased from 0.16 to 0.08 cm s-1, low dissolved oxygen concentration (DO) of 2.0 mg L-1 occurred in reactor. The required depth for anoxic microenvironment in biofilm decreased from 902.3 to 525.9 µm, which enhanced the growth of denitrifying bacteria and total nitrogen (TN) removal efficiency. However, decreasing aeration intensity resulted in insufficient hydraulic shear stress, which led to weak biofilm matrix structure. Mass biofilm detachment and reactor deterioration then occurred after 87 days of operation. An end gas recirculation aeration strategy was proposed to separately manipulate DO and aeration intensity. Low DO and high aeration intensity were simultaneously achieved, which enhanced the metabolism of denitrifying bacteria (such as Flavobacterium sp., Pseudorhodobacter sp., and Dok59 sp.) and EPS-producing bacteria (such as Zoogloea sp. and Rhodobacter sp.). Consequently, high TN removal performance (82.1 ± 2.7%) and stable biofilm structure were achieved.

The role of P2Y6 receptors in the maintenance of neuropathic pain and its improvement of oxidative stress in rats.

AIM: To explore the role of P2Y6 receptors in the maintenance of neuropathic pain and progression of oxidative stress, we investigated the efficacy of the selective P2Y6 receptors antagonist MRS2578 on the antiallodynic effects and improvement of pathological neuropathic pain-induced oxidative stress, thereby finding a potential therapeutic target in neurological disease. MATERIALS AND METHODS: The mechanical allodynia in the ipsilateral spinal dorsal horn (SDH) of rats was observed in rats after chronic constriction injury (CCI). Meanwhile, the messenger RNA (mRNA) levels of biological parameters, including superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1) in the SDH of rats were measured by real-time polymerase chain reaction (RT-PCR). In addition, the mRNA expression and protein levels of P2Y6 were measured by RT-PCR and Western blot assay, respectively. Next, the rats subjected to CCI were intrathecally infused with MRS2578 to block the expression of P2Y6 receptors. The positive expression of P2Y6 receptors was examined by immunohistochemistry. RESULTS: In the present study, the results revealed that the P2Y6 expression in the ipsilateral SDH of CCI rats was significantly upregulated. In addition, inhibition of the P2Y6 receptor in SDH increased CCI-induced tactile allodynia. Furthermore, the levels of SOD, GSH, and HO-1 which were correlated with oxidative stress produced by CCI were also decreased. CONCLUSION: The results demonstrated that inhibition of the P2Y6 receptor can generate antiallodynic effects and improved the pathological neuropathic pain-induced oxidative stress. Thus, this study provides a potential approach for the therapy of neurological disease.

Selective non-zinc binding MMP-2 inhibitors: Novel benzamide Ilomastat analogs with anti-tumor metastasis.

Novel Ilomastat analogs with substituted benzamide groups, instead of hydroxamic acid groups, were designed, synthesized and evaluated against MMP-2 and MMP-9. Among these analogs, the most potent compound 10a exhibited potent inhibitory activity against MMP-2 with IC50 value of 0.19 nM, which is 5 times more potent than that of Ilomastat (IC50=0.94 nM). Importantly, 10a exhibited more than 8300 fold selectivity for MMP-2 versus MMP-9 (IC50=1.58 µM). Molecular docking studies showed that 10a bond to the catalytic active pocket of MMP-2 by a non-zinc-chelating mechanism which was different from that of Ilomastat. Furthermore, the invasion assay showed that 10a was effective in reducing HEY cells invasion at 84.6% in 50 µM concentration. For 10a, the pharmacokinetic properties had been improved and especially the more desirable t1/2z was achieved compared with these of the lead compound Ilomastat.

Correlation between low tube voltage in dual source CT coronary artery imaging with image quality and radiation dose.

The influence of low tube voltage in dual source CT (DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index (BMI <18.5 kg/m(2)) subjected to DSCT coronary artery imaging were prospectively enrolled. The heart rate in all patients were greater than 65/min. The retrospective ECG gated scanning mode and simple random sampling method were used to assign the patients into groups A, B and C (n=100 each). The patients in groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging respectively, and the image quality was evaluated. The CT volume dose index (CTDIvol) and dose length product (DLP) were recorded, and the effective dose (ED) was calculated in each group. The image quality scores and radiation doses in groups were compared, and the influence of tube voltage on image quality and radiation dose was analyzed. The results showed that the excellent rate of image quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the difference being not statistically significant among the three groups (P>0.05). The CTDIvol values in groups A, B and C were 51.35±12.21, 21.28±7.13 and 6.34±3.34 mGy, respectively, with the difference being statistically significant (P<0.05). The ED values in groups A, B and C were 9.27±1.63, 4.56±2.29 and 2.29±1.69 mSv, respectively, with the difference being statistically significant (P<0.05). It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose.

Design, synthesis and cytotoxicity of novel 3'-N-alkoxycarbonyl docetaxel analogs.

By-product 9a exhibited potent cytotoxicity against both SK-OV-3 and A549 cell lines. The structure of 9a was characterized using 1D and 2D NMR experiments and confirmed by synthesis to afford a diastereomeric mixture (16a) that was identical to 9a, as well as a pair of diastereomers (R)-16b and (S)-16c. The preliminary SAR study demonstrated that analogs with an (R)-configuration were slightly more potent than analogs with an (S)-configuration. In addition, α,α-gem-dimethyl analogs 16 g-i were the most potent analogs in this series, exhibiting similar potency to docetaxel and greater potency than Taxol against the SK-OV-3 cell line. For the A549 cell line, analogs 16 g-i were more potent (>65-fold) than both docetaxel and Taxol.

Effect of qubi zhentong recipe on synovial gene expression in collagen-induced arthritis in rats.

OBJECTIVE: To investigate the effect of the Chinese medical formula Qubi Zhentong Recipe(, QZR) on the synovial gene expression profile in collagen-induced arthritis (CIA) rats. METHODS: Ten rats were randomly chosen from 60 rats as the control group, and the other 50 rats were used for the CIA models. The CIA model group was constructed by bovine injection of type II collagen through the rats' neck and tail. Twenty rats were randomly chosen from 34 successful CIA models and randomly assigned into two groups: the model group (n =10) and the QZR group (n=10). The QZR group was fed intragastrically with QZR 22.9 g/(kg·d) (10 times the clinical adult dose), and the CIA model group was given the same dose of normal saline. Both model and QZR groups were administered treatment once a day. Total RNA was collected from the knee joint synovium after 30 days. The change in gene expression profile was analyzed by a whole gene chip. RESULTS: A total of 76 genes showed a difference in expression between CIA model group and the control group; 35 genes were down-regulated and 41 were up-regulated. A total of 67 genes showed a difference in expression between the model group and the QZR group; 48 genes were down-regulated and 19 were upregulated. CONCLUSIONS: QZR may affect CIA by stimulating multiple genes and targets, which are related to oncogenes, apoptosis, metabolism, the immune system, ion channels, and transport proteins.

Synthesis and anti-HBV activity of novel 3'-N-phenylsulfonyl docetaxel analogs.

Nine new 3'-N-phenylsulfonyl docetaxel analogs were synthesized in good yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg secretion than the positive control lamivudine. Further extensive SAR and mechanistic studies will be reported in due course.

Synthesis and in vitro antitumor activity of novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands.

Four novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands were designed, synthesized, and characterized by FT-IR, NMR, and MS. The cytotoxicities of all of the complexes against the human solid tumor cell lines A2780, A549, KB, and MDA-MB-231 were evaluated. Both R,R-configured complexes (R,R)-5a and (R,R)-5b exhibited more potent or similar activity compared with oxaliplatin, whereas their corresponding (S,S)-isomers (S,S)-5a and (S,S)-5b were found to be mostly inactive. As indicated by the activation of caspase-3, the cleavage of PARP, and the upregulation of p53, the preliminary mechanism studies revealed that the mode of cell death initiated by (R,R)-5a in A2780 cells was predominantly p53-mediated apoptosis. In addition, the structure of (R,R)-5a was unambiguously confirmed through single crystal X-ray structure determination.

Mitochondrial-targeted prodrug cancer therapy using a rhodamine B labeled fluorinated docetaxel.

The aim of this work was to track the distribution and conversion of paclitaxel based prodrug by fluorescence imaging, which would help to up-regulate the therapeutic efficacy and reduce cytotoxicity of paclitaxel and docetaxel. We developed a novel prodrug for tumor treatment, in which a fluorinated docetaxel derivative, 4FDT as a chemotherapeutic reagent and rhodamine B as an imaging reporter as well as targeting domain were conjugated via a biodegradable ester bond. In vitro image studies demonstrated the morphological changes of tubulin and chromosomal alterations of human liver cancer cells HepG2, which were similar to the phenomena observed after treatment with the active drug 4FDT. At 48 h post-treatment, the cytotoxicity of 4FDT-RhB was 18.5% of that of 4FDT. However, this value increased to 49.3% of 4FDT at 72 h post-incubation. These experimental results implied the consistent release of the active drug from the prodrug throughout the incubation period via the linear increase in the cytotoxicity observed as a function of time. It also showed good stability in both plasma and complete blood. Additionally, the specific delivery of the prodrug to mitochondria was observed by fluorescent microscopy.

Inhibitory effect of resveratrol dimerized derivatives on nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells.

Four types of resveratrol dimerized analogues were synthesized and evaluated in vitro on LPS-induced NO production in RAW 264.7 cells. The results showed that several compounds, especially those containing 1,2-diphenyl-2,3-dihydro-1H-indene core (type I), exhibited good inhibitory activities. Among 25 analogues, 12b showed a significant inhibitory activity (49% NO production at 10 µM, IC50=3.38 µM). Further study revealed that compound 12b could suppress LPS-induced iNOS expression, NO production, and IL-1ß release in a concentration-dependently manner. The mechanism of action (MOA) involved for its anti-inflammatory responses was through signaling pathways of p38 MAPK and JNK1/2, but not ERK1/2.

[Effects of qubi zhentong recipe on the expressions of IL-1beta, IL-8, and VEGF in the synovial of rats with collagen-inducing arthritis].

OBJECTIVE: To research the effects of Qubi Zhentong Recipe (QZR) on the expressions of interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) in the synovial of rats with collagen-inducing arthritis (CIA), and to discuss its mechanisms of action. METHODS: Healthy male Wistar rats were recruited and randomly divided into the model group ( n = 50) and the normal control group (n = 10). Rats of the model group were injected with type II collagen of bovine (BC II) emulsion in the tail and nape to establish the CIA model. After successful modeling, 30 successfully modeled rats were selected and randomly divided into three groups, i.e., the model group (n = 10), the QZR group (n = 10), and the methotrexate (MTX) group (n = 10). Rats in the normal control group and the model group were administered with physiological saline by gastrogavage, while those in the QZR group were administered with QZR at 22.9 g/kg by gastrogavage. All medication was performed once daily. The rats in the MTX group were administered with MTX suspension at 0.78 mg/kg by gastrogavage, once per week. After 30-day treatment, the levels of IL-1beta, IL-8, and VEGF in the synovial were detected by immunohistochemical method. The arthritis index (AI) was scored before and after medication. RESULTS: After treatment the AL score of the QZR group and the MTX group was obviously lower than that of the model group (P < 0.01). The AI score of the two drug groups were lower than that before treatment (P < 0.01). Compared with the normal control group, the expression levels of IL-1beta, IL-8, and VEGF obviously increased in the model group (P < 0.01). Compared with the model group, the expression levels of IL-1beta, IL-8, and VEGF were significantly lower in the two drug groups (P < 0.01). But there was no statistical difference between the QZR group and the MTX group (P > 0.05). CONCLUSION: Decreasing the expression levels of IL-1beta, IL-8, and VEGF in the synovial of CIA rats may be one of the mechanisms for treating CIA by QZR.

Neuroprotective effects of mercaptoethylleonurine and mercaptoethylguanidine analogs on hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells.

A series of mercaptoethylleonurine and mercaptoethylguanidine derivatives were designed and synthesized. Their neuroprotective effects toward H2O2-induced apoptosis were investigated in human SH-SY5Y cells. The results from these studies identified several potent compounds, with compound 8k emerging as the most effective. Further investigation demonstrated that 8k reduced H2O2-induced activation of mitochondrial apoptosis by inhibiting the expression of Bax and elevating the expression of Bcl-2. Moreover, the molecular mechanism underlying the observed neuroprotective effects of 8k was exerted via the Akt and JNK pathways. Compound 8k can be a lead compound for further discovery of neuroprotective medicine.

[Observation on the analgesic effect of transcutaneous electrical acupoint stimulation for breast radical carcinoma operation].

OBJECTIVE: To observe the analgesic effect of transcutaneous electrical acupoint stimulation (TEAS) in assisting general anesthesia (GA) for radical operation of breast carcinoma so as to explore its clinical application value. METHODS: Sixty patients scheduled for radical operations of the breast carcinoma were randomly and equally divided into GA group and TEAS+ GA group. For GA, Propofol [4.5 microg/mL, target concentration; (3.0 +/- 0.5) microg/mL during operation] was used in combination with Sufentanil (0.25 microg/kg) and Cis-atracurium amine (0.2 mg/kg). TEAS (5-10 mA, 2 Hz/100 Hz) was applied to Hegu (LI 4)-Laogong (PC 8) and Neiguan (PC 6)-Waiguan (SJ 5) on the affected side of the body for 30 min. Heart rate (HR), mean aterial pressure (MAP), tube removing time and postoperative complications were recorded. Plasma beta-endorphin content was assayed by radioimmunoassay. RESULTS: After anesthesia, patients with reduction in MAP in GA group were significantly more than those in TEAS+GA group (P < 0.05), and their HR decreased remarkably (P < 0.05). After tracheal intubation, MAP in TEAS+GA group kept relatively stable, which was superior to that of GA group (P < 0.05). In comparison with GA group, the patients' analepsia time and tube withdrawal time of TEAS+ GA group were significantly shorter; and the dosage of analgesics of TEAS+GA group was significantly smaller than that of GA group (P < 0.05). Patients with complications of pain, restlessness, drowsiness, nausea and vomitting were obviously fewer in TEAS + GA group than those in GA group. Compared with GA group, plasma beta-endorphin content in TEAS+GA group increased considerably 30 min after TEAS, 5 min after skin-incision and after operation (P < 0.05). CONCLUSION: TEAS combined with general anesthesia for breast radical carcinoma operation can help keep a stable blood pressure during surgery, reduce the dosage of analgesics and strengthen pain relief. The analgesic effect of TEAS may be related to its effect in up-regulating plasma beta-endorphin level.

[Early superselective angiography and transarterial embolization for massive bleeding after gastrectomy].

OBJECTIVE: To evaluate the efficacy of early superselective angiography and embolization in the diagnosis and treatment of massive bleeding after gastrectomy. METHODS: The clinical data of 28 patients with massive bleeding after surgery from 1980 to 2001 were retrospectively analysed. All patients underwent emergency angiography and 27 of them were treated by transcatheter embolization. RESULTS: Bleeding was controlled in 26 of the 28 patients (93%), recurrent bleeding occurred in 1, an recognized bleeding in 1, and abdominal pain in 1. There was no death. CONCLUSIONS: Transarterial embolization for massive bleeding after gastrectomy is safe and effective. It is suggested that early emergency angiography should be considered in all patients with massive gastrointestinal bleeding after gastrectomy.