DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer.

BACKGROUND: CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells). MATERIALS AND METHODS: Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1. RESULTS: Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1. CONCLUSIONS: This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.

Artificial intelligence and open science in discovery of disease-modifying medicines for Alzheimer's disease.

The high failure rate of clinical trials in Alzheimer's disease (AD) and AD-related dementia (ADRD) is due to a lack of understanding of the pathophysiology of disease, and this deficit may be addressed by applying artificial intelligence (AI) to "big data" to rapidly and effectively expand therapeutic development efforts. Recent accelerations in computing power and availability of big data, including electronic health records and multi-omics profiles, have converged to provide opportunities for scientific discovery and treatment development. Here, we review the potential utility of applying AI approaches to big data for discovery of disease-modifying medicines for AD/ADRD. We illustrate how AI tools can be applied to the AD/ADRD drug development pipeline through collaborative efforts among neurologists, gerontologists, geneticists, pharmacologists, medicinal chemists, and computational scientists. AI and open data science expedite drug discovery and development of disease-modifying therapeutics for AD/ADRD and other neurodegenerative diseases.

Adaptation of anammox consortia in microbial fuel cell to low temperature: Microbial community and predictive functional profiling.

The purpose of this study was to explore the tolerance mechanism of anammox consortia in microbial fuel cell (MFC) system at low temperature. Data showed that nearly 80 % total nitrogen removal was achieved after the temperature decreased from 30 °C to 15 °C. The nitrogenremovalrate (NRR) of the system was decreased by 26.3 %, from 0.441 kgN·m-3·d-1 at 30 °C to 0.325 kgN·m-3·d-1 at 15 °C. Isotope experiment in 15NH4+-containing reactor found that much more 29N2 were produced than 30N2, confirming that anammox was the main 15NH4+ removal pathway and electrochemical oxidation participate in this process. High throughput sequencing analysis indicated the low temperature stimulated the enrichment of heterotrophic bacteria, such as Comamonadaceae and Rhodobacteraceae. While the relative abundance of Candidatus Brocadia, typical anammox bacteria, decreased significantly. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis showed that the low temperature induced a more efficient expression in synthesis of unsaturated fatty acids (UFAs) and ABC membrane transports. This study indicates that anammox consortia are likely to maintain high nitrogen removal performance of MFC system by changing the proportion of membrane composition and EPS exportation.

The role of histone chaperone spty2d1 in human colorectal cancer.

Colorectal cancer (CRC) remains a major public health concern, associated with a high rate of morbidity and mortality. Several factors have been implicated in its occurrence and development, which includes histone chaperones. The role of spty2d1 (spt2)-a novel histone chaperone protein-has rarely been investigated in CRC. Therefore, we demonstrated in this study that spt2 undergoes different genetic alterations in colorectal adenocarcinoma datasets and that it was associated with the proliferation of colon carcinoma. Spt2 silencing can reduce the ability of proliferation and increase the rate of apoptosis of LoVo cells. Regarding the overall survival associated with spt2, only the quartile disease-free survival of colon adenocarcinoma (COAD) was found to be statistically significant, while that of rectum adenocarcinoma (READ) was not. The positive (+++) expression of spt2 was correlated with a deeper invasion depth in colorectal adenocarcinoma, and this effect was more pronounced in COAD. These data collectively suggest that spt2 can influence the progression and prognosis in some subtypes of colorectal adenocarcinoma. Therefore, we propose spt2 as a potential target for application in enhancing the overall therapeutic efficacy in some specific subtypes of colorectal adenocarcinoma.

Mechanism of stable power generation and nitrogen removal in the ANAMMOX-MFC treating low C/N wastewater.

This study investigated the mechanism of enhanced power generation and nitrogen removal in an ANAMMOX-MFC reactor through subsequent acetate addition. Data showed that nearly 99% total nitrogen removal (≤1 mg L-1) and 1.41 W m-3 power generation were achieved synchronously under low COD/N (∼1.5) after the subsequent addition of acetate (100 mgCOD·L-1). The columbic efficiency of the system has increased by 15 times (from 0.64% to 9.48%) after adding acetate. Batch tests showed that the denitrification and ANAMMOX progress occurred synchronously before acetate addition the nitrogen removal rate was accelerated. A distinct shift of bacterial community driven by acetate addition was discovered. The high throughput sequencing analysis indicated acetate addition stimulated the enrichment of denitrifiers, such as Aquimonas, Bradyrhizobium, Thauera, and the potential exoelectrogens changing from Comamonas to Pseudomonas. Functional genes forecasts based on KEGG database and COG database showed that the expressions of TCA functional genes were highly promoted in ANAMMOX-MFC, which demonstrated the enhanced electron transfer pathway driven by acetate addition under low COD/N ratio.

Low-strength influence on nitrogen removal performance and bacterial community structure of the anammox process.

The effect of low strength on anaerobic ammonium oxidation (anammox) was investigated in an anaerobic moving bed biofilm reactor (AMBBR) treating artificial wastewater. Influent NH4+-N concentration with 10.74 ± 2.73 mg L-1 adversely impacted nitrogen removal permanence, the total nitrogen removal efficiency was significantly increased from 61.4% to 80.0%, when influent nitrogen increased to 22.36 ± 5.83 mg·L-1. NH4+-N removal efficiency decreased obviously while that of NO2--N was basically unaffected by the influent nitrogen concentration decrease. Illumina high-throughput sequencing results revealed that the predominant bacterial (64.71%) phylum was Proteobacteria and the dominant functional microorganisms were Nitrosospira, Nitrospira, and Candidatus Brocadia. Simple model simulation results showed that the inhibition effect of the low substrate was most likely due to the increase of bulk DO, which comes from influent and gas-liquid transfer. The reversible inhibition effect of low strength on nitrogen removal performance in an anammox reactor was demonstrated, and strictly regulation of the bulk DO was presumed to be critical to achieve a successful and stable operating performance under low strength.

Genistein inhibits lung cancer cell stem-like characteristics by modulating MnSOD and FoxM1 expression.

Manganese superoxide dismutase (MnSOD) promotes invasive and migratory activities by upregulating Forkhead box protein M1 (FoxM1) expression. The present study investigated whether modulation of MnSOD and FoxM1 expression was responsible for the antitumor effects of genistein on cancer stem-like cells (CSLCs) derived from non-small cell lung cancer cells (NSCLCs). Spheroids prepared from H460 or A549 cells were defined as lung cancer stem-like cells (LCSLCs) and were treated with genistein. The Cell Counting Kit-8 assay was performed to assess human lung fibroblast IMR-90 cell proliferation, as well as NSCLC H460 and A549 cell proliferation following treatment with genistein. MnSOD, FoxM1, cluster of differentiation (CD)133, CD44, BMI1 proto-oncogene, polycomb ring finger (Bmi1) and Nanog homeobox (Nanog) protein expression levels were examined via western blotting. The sphere formation assay was conducted to evaluate LCSLC self-renewal potential, and LSCLC migratory and invasive activities were analyzed using the wound healing and Transwell invasion assays, respectively. Knockdown and overexpression of MnSOD and FOXM1 via short hairpin-RNA or cDNA transfection were performed. The results indicated that genistein (80 and 100 µM) suppressed H460 and A549 cell viability compared with IMR-90 cells. Sub-cytotoxic concentrations of genistein (20 and 40 µM) inhibited sphere formation activity and decreased the protein expression levels of CD133, CD44, Bmi1 and Nanog in LCSLCs compared with the control group. Genistein also suppressed the migratory and invasive activities of LCSLCs compared with the control group. MnSOD and FoxM1 overexpression antagonized the effects of genistein (40 µM), whereas MnSOD and FoxM1 knockdown enhanced the inhibitory effects of genistein (20 µM) on CSLC characteristics of LCSLCs. Overall, the results suggested that genistein suppressed lung cancer cell CSLC characteristics by modulating MnSOD and FoxM1 expression levels.

Quinoline's influence on nitrogen removal performance and microbial community composition of the anammox process.

This study aimed to evaluate the effects of quinoline on nitrogen removal performance and microbial community of an anaerobic biofilm reactor with anammox activity. Results showed that 20 mg L-1 quinoline addition leading the ammonia and nitrite removal efficiency of the ABR reduced from about 90% to 40%. Illumina MiSeq sequencing study indicated that microbial community structure and composition varied with the additive of quinoline. Planctomycetes and Bacteroidetes, decreased in abundance, suggested that quinoline adversely affects the anammox metabolism within the anammox reactor. The distribution of the anammox bacteria was affected by quinoline addition. Ca. Jettenia prevailed over the other two anammox bacteria (Brodica and Kuenenia) in the recovered phase.

Upregulation of FoxM1 by MnSOD Overexpression Contributes to Cancer Stem-Like Cell Characteristics in the Lung Cancer H460 Cell Line.

Manganese superoxide dismutase promotes migration and invasion in lung cancer cells via upregulation of the transcription factor forkhead box M1. Here, we assessed whether upregulation of forkhead box M1 by manganese superoxide dismutase overexpression mediates the acquisition of cancer stem-like cell characteristics in non-small cell lung cancer H460 cells. The second-generation spheroids from H460 cells were used as lung cancer stem-like cells. The levels of manganese superoxide dismutase, forkhead box M1, stemness markers (CD133, CD44, and ALDH1), and transcription factors (Bmi1, Nanog, and Sox2) were analyzed by Western blot. Sphere formation in vitro and carcinogenicity of lung cancer stem-like cells were evaluated by spheroid formation assay and limited dilution xenograft assays. Knockdown or overexpression of manganese superoxide dismutase or/and forkhead box M1 by transduction with short hairpin RNA(shRNA) or complementary DNA were performed for mechanistic studies. We showed that manganese superoxide dismutase and forkhead box M1 amounts as well as the expression levels of stemness markers and transcription factors sphere formation in vitro, and carcinogenicity of lung cancer stem-like cells were higher than in monolayer cells. Lung cancer stem-like cells transduced with manganese superoxide dismutase shRNA or FoxM1 shRNA exhibited decreased sphere formation and lower amounts of stemness markers and transcription factors. Overexpression of manganese superoxide dismutase or FoxM1 in H460 cells resulted in elevated sphere formation rates and protein levels of stemness markers and transcription factors. Meanwhile, manganese superoxide dismutase knockdown or overexpression accordingly altered forkhead box M1 levels. However, forkhead box M1 knockdown or overexpression had no effect on manganese superoxide dismutase levels but inhibited or promoted lung cancer stem-like cell functions. Interestingly, forkhead box M1 overexpression alleviated the inhibitory effects of manganese superoxide dismutase knockdown in lung cancer stem-like cells. In a panel of non-small cell lung cancer cells, including H441, H1299, and H358 cells, compared to the respective monolayer counterparts, the expression levels of manganese superoxide dismutase and forkhead box M1 were elevated in the corresponding spheroids. These findings revealed the role of forkhead box M1 upregulation by manganese superoxide dismutase overexpression in maintaining lung cancer stem-like cell properties. Therefore, inhibition of forkhead box M1 upregulation by manganese superoxide dismutase overexpression may represent an effective therapeutic strategy for non-small cell lung cancer.

An anoxic-aerobic system for simultaneous biodegradation of phenol and ammonia in a sequencing batch reactor.

A laboratory-scale sequencing batch reactor (SBR) was investigated to treat artificial pretreated coal gasification wastewater that was mainly contained of ammonia and phenol. The efficiency of SBR fed with increasing phenol concentrations (from 150 to 300 mg l-1) and the relationship among phenol, nitrogen removal, and the microbial community structure were evaluated. When the phenol feeding concentration was increased to about 300 mg l-1, the removal efficiency was above 99.0%, demonstrating the robustness of phenol removal capacity. The study showed that most phenol was degraded in anoxic stage. The average removal efficiencies of ammonia and total nitrogen were 98.4 and 81.9%, respectively, with average NH4+-N concentration of 107.5 mg l-1 and COD/N 7.5. Low temperature caused sludge loss that led to the decreased performance. Increasing the temperature could not recover the performance effectively. The data from bacterial analysis revealed that Delftia, Hydrogenophaga, and unclassified Xanthomonadaceae played a significant role in phenol degradation before the temperature increase, while uncultured Syntrophococcus sp. and unclassified Rhodocyclaceae were responsible for phenol degradation after the temperature increase. These results imply that the SBR holds potential for the simultaneous removal of phenolic compounds and nitrogen through aerobic ammonia oxidation and anoxic denitrification with phenol as the co-organic carbon source.

Regio- and Stereoselective Hydrosulfonation of Alkynylcarbonyl Compounds with Sulfinic Acid in Water.

We report the atom-economic and environmentally friendly synthesis of Z-ß-sulfonyl-a,ß-unsaturated carbonyl compounds in water. The mechanism study reveals that the hydrosulfonylation of alkynylcarbonyl compounds with sulfinic acids proceeds via a mechanism that features a sulfinic acid molecule protonating an alkynyl motif to form the ethenium intermediate, which subsequently reacted with a sulfonyl anion to afford the desired products. The ethenium intermediate differentiated electronic and steric demands between the two substituents on the C≡C triple bond of the alkyne substrates to exhibit high regio- and stereoselectivity from a wide range of Z-ß-sulfonyl-a,ß-unsaturated carbonyl compounds.

Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells.

We aimed to explore the effects of raloxifene (RAL) on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs). Different concentrations of RAL were used to act on AVICs. MTS kit is used to test the effects of different concentrations of RAL on the proliferation of AVICs. Cell cycle and apoptosis test used flow cytometry after seven-day treatment. The relative expression levels of caspase-3 and caspase-8 are tested with RT-qPCR and Western blot. The results of MTS testing revealed that the absorbance value (OD value) of the cells in the concentration groups of 10 and 100 nmol/L RAL at a wavelength of 490 nm at five, seven, and nine days significantly decreased compared with that in the control group. Meanwhile, the results of flow cytometry of the cells collected after seven days showed that the ratio of the S stage and the cell apoptosis rate of AVICs can be significantly reduced by RAL in the concentration groups of 10 and 100 nmol/L. The mRNA and protein expressions of caspase-3 and caspase-8 were significantly decreased compared with those in the control group. This study laid the foundation for further treatment of aortic valve disease by using RAL.

Impact of quinoline on activity and microbial culture of partial nitrification process.

In this study, the effect of quinoline on nitrification in an activated sludge system was evaluated in batch assays. Quinoline was evaluated to partial nitrification process or to partial nitrification-quinoline degrading process. In partial nitrification assays, 50-150mg/L quinoline presence promoted the ammonium oxidation efficiency (200-100%). Nonetheless, the consumption efficiencies for quinoline were less than 66.6%. On the other hand, in partial nitrification-quinoline degrading process, the promotion effect of quinoline (50-150mg/L) diminished significantly, ammonium oxidation were similarity to the control. However, the consumption efficiencies for quinoline were nearly 100%. DGGE results showed that the bacteria communities varied significantly. Acidovorax sp. JS42 and Acidovorax ebreus TPSY were responsible for ammonium oxidation in partial nitrification process, while Nitrosomonas in partial nitrification-quinoline degrading process. This information might be useful for treating wastewaters of ammonium/quinoline by partial nitrification technology.

Ammonia and phenol removal in an internal-circulate sequencing batch airlift reactor.

An internal-circulate sequencing batch airlift reactor (IC-SBAR) has been developed to evaluate the efficiency of phenol and ammonia removal in treating synthetic wastewater. This study examined the effect of operation cycle on this system. Results showed that above 97.0% removal efficiencies of ammonia and phenol were achieved, which indicated that ammonia and phenol removals were not related to operation cycle. The average removal efficiency of 91.7% for chemical oxygen demand (COD) was achieved when the static/aerobic/settling time was 240 min/440 min/40 min. It was found that COD removal efficiency increased due to the time of operation cycle being prolonged. The average removal efficiencies of total inorganic nitrogen (TIN) were 65.8, 69.3 and 68.9% when average TIN concentrations were 78.0, 97.6 and 88.4 mg/L, respectively, in the influent. A cycle study showed that most phenol was degraded by aerobic microbes. Increasing the static time from 120 to 240 min resulted in the accumulation of NO2(-)-N, which indicated that the structures of the nitrifying bacterial community were changed.

Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1 in lung adenocarcinoma pleural effusions predicts survival in patients receiving platinum-based chemotherapy.

The association between the expression of excision repair cross­complementing gene 1 (ERCC1), thymidylate synthase (TYMS), ribonuleotide reductase M1 (RRM1), ßIII­tubulin (TUBB3), non­muscle myosin II, myoglobin and MyoD1 in metastatic lung adenocarcinoma, and clinical outcomes with platinum­based chemotherapy treatment is not well­established. Recently, increasing attention has been focused on the involvement of ERCC1, TYMS, RRM1 and TUBB3 in the development of drug resistance. There has been less research into the role of muscle myosin II, myoglobin and MyoD1 in the pathogenesis of lung cancer, although these genes are known to have important functions within tumor cells. In the current study, malignant pleural effusion from 116 patients with untreated lung adenocarcinoma diagnosed between 2011 and 2012, were collected. The protein expression levels of ERCC1, TYMS, RRM1 and TUBB3 were evaluated with immunocytochemistry and western blot analysis. The expression levels of non­muscle myosin II, myoglobin and MyoD1 were measured in a subset of 50 patients, treated with platinum­based chemotherapy. The association of each of these seven factors with one another, as well as with patient survival were analyzed. Immunohistochemistry demonstrated that the percentage of pleural fluid samples from patients with lung adenocarcinoma expressing ERCC1, TYMS, RRM1 and TUBB3 was 37, 36.2, 82.7 and 69.8%, respectively. In the subset of 50 patients in whom the remaining factors were analyzed, the percentage expressing non­muscle myosin II was 48%, for myoglobin the figure was 40% and for MyoD1 it was 38%. There was a positive correlation between each pair of the above seven molecules with the exception of TYMS and RRM1. Expression of ERCC1, TYMS, TUBB3, non­muscle myosin II, myoglobin and MyoD1 genes was associated with decreased survival in patients with metastatic lung adenocarcinoma. Expression of ERCC1, TYMS, TUBB3, non­muscle myosin II, myoglobin and MyoD1 was also associated with decreased survival rates of patients with lung adenocarcinoma treated with platinum­based chemotherapy. These factors may be used as clinical biomarkers to predict the biological behavior and chemoresistance of tumor cells, and the survival of patients with lung carcinoma.

Transcription expression and clinical significance of mRNA of vascular endothelial growth factor and endostatin in liquid-based preparation specimens from patients with cervical dysplasia and carcinoma.

OBJECTIVES: The aim of this study was to assess the diagnostic usefulness of vascular endothelial growth factor (VEGF) and endostatin mRNA in cervical specimens of patients with cervical dysplasia and carcinoma. STUDY DESIGN: Transcription levels of VEGF and endostatin were detected by RT-PCR in cervical liquid-based preparation specimens and compared with cytological assessments. RESULTS: VEGF as well as endostatin mRNA expression was significantly associated with either cytological or histological diagnosis (p < 0.05). VEGF mRNA and endostatin mRNA were significantly more likely to be expressed in squamous cell carcinomas (SCC) than in cervical intraepithelial neoplasia (CIN) III (p < 0.01 and p < 0.05), and obviously also more likely to be expressed in CINII than in CINI and in CINIII than in CINII (p < 0.05). Eleven inflammation lesions gave positive results by cytology but negative results by RT-PCR for VEGF and endostatin mRNA. Twenty-four SCC lesions gave false-negative or precancerous lesion results by cytology but positive results by RT-PCR for VEGF and/or endostatin mRNA expression. CONCLUSION: Transcription levels of VEGF and endostatin by RT-PCR may be an adjunct to cytology screening for early detection of cervical carcinomas and may determine the progressive potentiality of individual lesions, especially in high-risk patients.

[Study on number concentration distribution of atmospheric ultrafine particles in Hangzhou].

Atmospheric ultrafine particles (UFPs) were measured with fast mobility particle sizer(FMPS) in Hangzhou, during March 2011 to February 2012. The number concentration and size distribution of UFPs associated with meteorology were studied. The results showed that the number concentration of UFPs was logarithmic bi-modal distribution, and the seasonal levels presented winter > summer > spring> autumn. The highest monthly average concentration was 3.56 x 10(4) cm-3 in December and the lowest was 2.51 x 10(4) cm-3 in October. The seasonal values of count medium diameter(CMD) were spring > winter > autumn > summer. The highest monthly average CMD was 53. 51 nm in April and the lowest was 16.68 nm in June. Meteorological factors had effects on concentration of UFPs.

Effect of pitavastatin in different SLCO1B1 backgrounds on repaglinide pharmacokinetics and pharmacodynamics in healthy Chinese males.

The effect of pitavastatin and SLCO1B1 genetic background on the pharmacokinetic and pharmacodynamic properties of repaglinide was investigated. In this randomized, placebo-controlled, crossover study, twelve healthy Chinese males were administered with pitavastatin 4 mg/d or the placebo for 5 d followed by repaglinide 4 mg given orally on d 5. Plasma repaglinide and glucose levels were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the glucose oxidase method, respectively. Treatment with pitavastatin significantly increased the peak plasma concentration (Cmax) of repaglinide (P=0.003) in SLCO1B1*1b homozygotes (P=0.015) and SLCO1B1*15 carriers (P=0.031). Treatment with pitavastatin led to a marginal increase in the area under plasma concentration-time curve from 0 h to infinity (AUC0⇒∞) of repaglinide (P=0.091). There was no significant difference in pharmacokinetic parameters or hypoglycemic effects of repaglinide among SLCO1B1 genotypes in either the pitavastatin or control group. Pitavastatin increased the Cmax of the plasma concentration of repaglinide in an SLCO1B1 genotype dependent manner, but had no apparent effect on the pharmacodynamics of repaglinide in healthy volunteers. The p values for this statement were not reported.

Effects of the CYP oxidoreductase Ala503Val polymorphism on CYP3A activity in vivo: a randomized, open-label, crossover study in healthy Chinese men.

BACKGROUND: Cytochrome P450 (CYP) oxidoreductase (POR) is the electron donor for microsomal CYP enzymes. The POR Ala503Val (POR*28 C > T) polymorphism has been reported to influence CYP3A activity in vivo in a white population. The influence of this polymorphism on CYP3A activity in vivo in the Chinese population currently unknown. OBJECTIVE: This study was designed to assess the influence of the POR*28 polymorphism on the CYP3A activity in vivo in healthy Chinese men using midazolam (MID) as a probe drug. METHODS: The POR*28 polymorphism was genotyped in healthy Chinese men. A randomized, 2-phase, open-label, crossover study was performed to assess in vivo CYP3A activity after both oral and intravenous MID administration, which reflect both intestinal and hepatic CYP3A or only hepatic CYP3A activity, respectively. The plasma concentrations of MID and 1-hydroxy-midazolam (1-OH-MID) were determined by liquid chromatography-tandem mass spectrometry. RESULTS: A total of 73 healthy Chinese men were enrolled (CC genotype, 21 subjects; TT genotype, 11; CT genotype, 41), 22 of whom were selected for additional phenotyping of the CYP3A5*3 polymorphism (CC, 7; TT, 8; CT, 7). The mean (range) age, weight, height, and body mass index of the 22 subjects were 23 (20-28) years, 65.0 (57-75) kg, 1.74 (1.63-1.80) m, and 22.01 (19.27-24.46) kg/m(2), respectively. The frequency of the POR*28 T (503V) allele was 43.2%. No significant differences in the demographic characteristics of the subjects were observed between the POR*28 genotype groups. All of the POR*28 CC and TT homozygotes and 2 of the POR*28 CT heterozygotes carried the CYP3A5*3/*3 genotype (CYP3A5 low expressors); 6 CT heterozygotes carried the CYP3A5*1 allele (CYP3A5 expressors). The mean (SD) 1-OH-MID AUC(0-8) was significantly greater in the TT homozygotes compared with the CT heterozygotes after intravenous (86.15 [24.34] vs 53.21 [31.36] ng/mL/h; P = 0.026) but not oral (126.36 [31.60] vs 103.09 [31.00] ng/mL/h; P = 0.159) MID administration. Mean 1-OH-MID C(max) was significantly greater in the TT homozygotes (51.40 [10.72] ng/mL) compared with the CC homozygotes (31.47 [11.54] ng/mL; P = 0.002) and CT heterozygotes (30.12 [9.21] ng/mL; P = 0.001) after intravenous MID administration. After intravenous MID injection, the MID metabolic ratio was significantly greater in the TT homozygotes compared with carriers of the C allele (P = 0.031). Based on these findings, no significantly differences in overall (hepatic plus intestinal) CYP3A in vivo activity were observed between the POR*28 genotypes. CONCLUSION: These findings suggest that individuals with the POR*28 C > T polymorphism underwent an increase in 1-hydroxylation of MID after intravenous MID administration, and that the polymorphism was associated with increased hepatic, but not intestinal, CYP3A activity in these healthy Chinese volunteers.

Textiles wastewater treatment using anoxic filter bed and biological wriggle bed-ozone biological aerated filter.

In this study, the performance of the anoxic filter bed and biological wriggle bed-ozone biological aerated filter (AFB-BWB-O(3)-BAF) process treating real textile dyeing wastewater was investigated. After more than 2 month process operation, the average effluent COD concentration of the AFB, BWB, O(3)-BAF were 704.8 mg/L, 294.6 mg/L and 128.8 mg/L, with HRT being 8.1-7.7h, 9.2h and 5.45 h, respectively. Results showed that the effluent COD concentration of the AFB decreased with new carriers added and the average removal COD efficiency was 20.2%. During operation conditions, HRT of the BWB and O(3)-BAF was increased, resulting in a decrease in the effluent COD concentration. However, on increasing the HRT, the COD reduction capability expressed by the unit carrier COD removal loading of the BWB reactor increased, while that of the O(3)-BAF reactor decreased. This study is a beneficial attempt to utilize the AFB-BWB-O(3)-BAF combine process for textile wastewater treatment.