Shared Genetic Architecture between Parkinson's Disease and Brain Structural Phenotypes.

BACKGROUND: Patients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood. OBJECTIVE: The aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci. METHODS: We used the summary statistics from genome-wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed. RESULTS: MiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function-related biological processes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune-related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society.

Identifying causal genes for migraine by integrating the proteome and transcriptome.

BACKGROUND: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine. METHODS: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes. RESULTS: We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine. CONCLUSIONS: Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine.

Biodegradation of flonicamid by Ensifer adhaerens CGMCC 6315 and enzymatic characterization of the nitrile hydratases involved.

BACKGROUND: Flonicamid (N-cyanomethyl-4-trifluoromethylnicotinamide, FLO) is a new type of pyridinamide insecticide that regulates insect growth. Because of its wide application in agricultural production and high solubility in water, it poses potential risks to aquatic environments and food chain. RESULTS: In the present study, Ensifer adhaerens CGMCC 6315 was shown to efficiently transform FLO into N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) via a hydration pathway mediated by two nitrile hydratases, PnhA and CnhA. In pure culture, resting cells of E. adhaerens CGMCC 6315 degraded 92% of 0.87 mmol/L FLO within 24 h at 30 °C (half-life 7.4 h). Both free and immobilized (by gel beads, using calcium alginate as a carrier) E. adhaerens CGMCC 6315 cells effectively degraded FLO in surface water. PnhA has, to our knowledge, the highest reported degradation activity toward FLO, Vmax = 88.7 U/mg (Km = 2.96 mmol/L). Addition of copper ions could increase the enzyme activity of CnhA toward FLO by 4.2-fold. Structural homology modeling indicated that residue ß-Glu56 may be important for the observed significant difference in enzyme activity between PnhA and CnhA. CONCLUSIONS: Application of E. adhaerens may be a good strategy for bioremediation of FLO in surface water. This work furthers our understanding of the enzymatic mechanisms of biodegradation of nitrile-containing insecticides and provides effective transformation strategies for microbial remediation of FLO contamination.

Bioconversion of indole-3-acetonitrile by the N2-fixing bacterium Ensifer meliloti CGMCC 7333 and its Escherichia coli-expressed nitrile hydratase.

An N2-fixing bacterium, Ensifer meliloti CGMCC 7333, has been reported to degrade the cyano-containing neonicotinoid insecticides acetamiprid and thiacloprid using a nitrile hydratase (NHase). Here, the bioconversion of indole-3-acetonitrile (IAN) by E. meliloti, Escherichia coli overexpressing the NHase, and purified recombinant NHase was studied. E. meliloti converted IAN to the product indole-3-acetamide (IAM), and no nitrilase or amidase activities, or indole-3-acetic acid formation, were detected. Whole cells of E. meliloti converted IAN from the initial content of 6.41 to 0.06 mmol/L in 48 h. Meanwhile, forming 5.99 mmol/L IAM, the molar conversion of 94.4%. E. coli Rosetta overexpressing the NHase from E. meliloti produced 4.46 mmol/L IAM in 5 min, with a conversion rate of 91.1%. The purified NHase had a Vmax for IAN conversion of 294.28 U/mg. Adding 2% and 10% (v/v) dichloromethane to 50 mmol/L sodium phosphate buffer containing 200 mg/L IAN increased the NHase activity by 26.8% and 11.5% respectively, while the addition of 20% hexane had no inhibitory effect on IAN bioconversion. E. meliloti shows high NHase activity without forming a byproduct carboxylic acid, and its tolerance of dichloromethane and hexane increases its potential for application in the green biosynthesis of high-value amide compounds.

The Plant Growth-Promoting Rhizobacterium Variovorax boronicumulans CGMCC 4969 Regulates the Level of Indole-3-Acetic Acid Synthesized from Indole-3-Acetonitrile.

Variovorax is a metabolically diverse genus of plant growth-promoting rhizobacteria (PGPR) that engages in mutually beneficial interactions between plants and microbes. Unlike most PGPR, Variovorax cannot synthesize the phytohormone indole-3-acetic acid (IAA) via tryptophan. However, we found that Variovorax boronicumulans strain CGMCC 4969 can produce IAA using indole-3-acetonitrile (IAN) as the precursor. Thus, in the present study, the IAA synthesis mechanism of V. boronicumulans CGMCC 4969 was investigated. V. boronicumulans CGMCC 4969 metabolized IAN to IAA through both a nitrilase-dependent pathway and a nitrile hydratase (NHase) and amidase-dependent pathway. Cobalt enhanced the metabolic flux via the NHase/amidase, by which IAN was rapidly converted to indole-3-acetamide (IAM) and in turn to IAA. IAN stimulated metabolic flux via the nitrilase, by which IAN was rapidly converted to IAA. Subsequently, the IAA was degraded. V. boronicumulans CGMCC 4969 can use IAN as the sole carbon and nitrogen source for growth. Genome sequencing confirmed the IAA synthesis pathways. Gene cloning and overexpression in Escherichia coli indicated that NitA has nitrilase activity and IamA has amidase activity to respectively transform IAN and IAM to IAA. Interestingly, NitA showed a close genetic relationship with the nitrilase of the phytopathogen Pseudomonas syringae Quantitative PCR analysis indicated that the NHase/amidase system is constitutively expressed, whereas the nitrilase is inducible. The present study helps our understanding of the versatile functions of Variovorax nitrile-converting enzymes that mediate IAA synthesis and the interactions between plants and these bacteria.IMPORTANCE We demonstrated that Variovorax boronicumulans CGMCC 4969 has two enzymatic systems-nitrilase and nitrile hydratase/amidase-that convert indole-3-acetonitrile (IAN) to the important plant hormone indole-3-acetic acid (IAA). The two IAA synthesis systems have very different regulatory mechanisms, affecting the IAA synthesis rate and duration. The nitrilase was induced by IAN, which was rapidly converted to IAA; subsequently, IAA was rapidly consumed for cell growth. The nitrile hydratase (NHase) and amidase system was constitutively expressed and slowly but continuously synthesized IAA. In addition to synthesizing IAA from IAN, CGMCC 4969 has a rapid IAA degradation system, which would be helpful for a host plant to eliminate redundant IAA. This study indicates that the plant growth-promoting rhizobacterium V. boronicumulans CGMCC 4969 has the potential to be used by host plants to regulate the IAA level.

Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP.

Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing in a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C→T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein). CHIP plays a central role in regulating protein quality control, in part through its ability to function as an E3 ligase. Loss of CHIP function has long been associated with protein misfolding and aggregation in several genetic mouse models of neurodegenerative disorders; however, a role for CHIP in human neurological disease has yet to be identified. Introduction of the Thr246Met mutation into CHIP results in a loss of ubiquitin ligase activity measured directly using recombinant proteins as well as in cell culture models. Loss of CHIP function in mice resulted in behavioral and reproductive impairments that mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss-of-function mutation in CHIP. Our findings further highlight the role of disordered ubiquitination and protein quality control in the pathogenesis of neurodegenerative disease and demonstrate the utility of combining whole-exome sequencing with molecular analyses and animal models to define causal disease polymorphisms.

Exome capture sequencing identifies a novel CCM1 mutation in a Chinese family with multiple cerebral cavernous malformations.

PURPOSE: Cerebral cavernous malformations (CCMs) are vascular anomalies predominantly in the central nervous system but may include lesions in other tissues, such as the retina, skin and liver. The main clinical manifestations include seizures, hemorrhage, recurrent headaches and focal neurological deficits. Previous studies of familial CCMs (FCCMs) have mainly reported in Hispanic and Caucasian cases. Here, we report on FCCMs in a Chinese family further characterized by a novel CCM1 gene mutation. MATERIALS AND METHODS: We investigated clinical and neuroradiological features of a Chinese family of 30 members. Furthermore, we used exome capture sequencing to identify the causing gene. The CCM1 mRNA expression level in three patients of the family and 10 wild-type healthy individuals were detected by real-time quantitative polymerase chain reaction (real-time RT-PCR). RESULTS: Brain magnetic resonance imaging demonstrated multiple intracranial lesions in seven members. The clinical manifestation of CCM was found in five of these cases, including recurrent headaches, weakness, hemorrhage and seizures. Moreover, we identified a novel nonsense mutation c.1159G>T (p. E387*) in the CCM1 gene in the pedigree. Based on real-time RT-PCR results, we have found that the CCM1 mRNA expression level in three patients was reduced by 35% than that in wild-type healthy individuals. CONCLUSIONS: Our finding suggests that the novel nonsense mutation c.1159G>T in CCM1 gene is associated with FCCM, and that CCM1 haploinsufficiency may be the underlying mechanism of CCMs. Furthermore, it also demonstrates that exome capture sequencing is an efficient and direct diagnostic tool to identify causes of genetically heterogeneous diseases.

Co-metabolic transformation of the neonicotinoid insecticide imidacloprid by the new soil isolate Pseudoxanthomonas indica CGMCC 6648.

A new imidacloprid (IMI) degrading bacterium Z-9 (deposited number CGMCC 6648) was isolated and identified as Pseudoxanthomonas indica by 16S rRNA gene analysis. Two metabolites were identified as olefin and 5-hydroxy IMI by liquid chromatography-mass spectrometry and nuclear magnetic resonance analysis. P. indica CGMCC 6648 degraded 70.1% of IMI (1.22 mmol L(-1)) and formed 0.93 mmol L(-1) 5-hydroxy IMI and 0.05 mmol L(-1) olefin IMI in 6 days and in the presence of 100 mmol L(-1) glucose. The half-life of IMI degradation was 3.6 days. P. indica CGMCC 6648 transforms IMI via a co-metabolism mechanism and different carbohydrates have significant effects on 5-hydroxy IMI formation, whereas different organic acids have substantial effects on olefin IMI production. Lactose is the best co-substrate for IMI degradation and 5-hydroxy IMI formation with 0.77 mmol L(-1) degraded and 0.67 mmol L(-1) formed in 48 h, respectively. Pyruvate is the best co-substrate for olefin IMI formation with 0.17 mmol L(-1) produced in 96 h for all carbon sources tested. Pyruvate significantly stimulates the conversion of 5-hydroxy IMI to olefin IMI, whereas glucose slightly inhibits this reaction. P. indica CGMCC 6648 rapidly degrades IMI and forms olefin IMI, which may enhance its potential for biodegradation of IMI and increase its insecticidal activity, which can decrease the IMI dosage required.

[Validation of ABCD3 score in the predication of stroke risk after transient ischemic attack].

UNLABELLED: Objective To explore the evaluation of ABCD(3) score in the prediction of stroke risk after transient ischemic attack and the influencing factors of early stroke risks. METHODS: From October 2010 to September 2012, the data were prospectively collected from patients with transient ischemic attack according to the World Health Organization time-based criteria. ABCD(2) and ABCD(3) scores were available within 7 days of index transient ischemic attack. The predictive outcome was stroke occurrence at 90 days. Risks of stroke stratified according to the score were analysed by Logistic regression. And ABCD(2) and ABCD(3) model were compared by AUROCC. RESULTS: Among 321 eligible patients, 4 cases were lost to follow-up. There were 38(11.8%) patients with ischemic stroke during a 90-day follow-up, including 22(57.9%) males, 16(42.1%) females. There were no occurrence of death, no hemorrhagic stroke. Multivariate analysis revealed that dual TIA (OR = 4.116, 95%CI 1.284-3.195) , history of stroke (OR = 4.022, 95%CI 1.472-10.944) and unilateral weakness (OR = 3.117, 95%CI 1.222-7.948) were the risk factors of early stroke. The ABCD(3) score (0.733, 95% CI,0.0.681-0.780) was statistically higher than that of ABCD(2) score (0.674, 95%CI, 0.619-0.725) (P < 0.05). CONCLUSION: ABCD(3) may effectively predict early risk of stroke after TIA.

Erratum: SNHG3 promotes migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the miR-186-5p/ZEB1 axis.

[This corrects the article on p. 585 in vol. 13, PMID: 33594311.].

[Protective effects of estrogen modified hBMSC on HG-induced injury of vascular endothelial cells].

Objective: To investigate the protective effects and potential mechanisms of estrogen modified human bone marrow mesenchymal stem cells (hBMSC) on high glucose (HG)-induced injury of vascular endothelial cells. Methods: hBMSCs were cultured under 30 mmol/l glucose to establish a high glucose model (HG), and then were divided into four groups as following: HG group (HG control, without any treatment), HG+E2 group (cells were treated with 20 µmol/L estrogen), HG+E2+ Triciribine group (cells were pretreated with 5 µmol/L protein kinase B (PKB/Akt) inhibitor for 45 min, and then modified by 20 µmol/L estrogen), and NG group (cells were cultured under normal conditions). After 12 h treatment, the cell viability of hBMSC was detected by CCK8 assay, and the contents of NO, VEGF and IL8 in the supernatant of cultured medium in each group were detected by nitrate reductase and ELISA assay (n=6). After 48 h, the expression levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) were detected by Western blot (n=3). In addition, the cell supernatant of each group was further extracted as conditioned medium to culture HUVECs, and the cells were subsequently divided into HG-CM group (HUVECs were treated with HG group's conditioned medium), HG+E2-CM group (HUVECs were treated with HG+E2 group's conditioned medium), HG+E2+Triciribine-CM group (HUVECs were treated with HG+E2+ Triciribine group's conditioned medium) and HG-H group (HUVEC were cultured under HG condition, which were treated with final concentration 30 mmol/l glucose). The cell viability of HUVECs in each group was detected by CCK8 assay after 12 h cultured (n=6). After 24 h treatment, the apoptosis rate of HUVECs in each group was detected by flow cytometry (n=3). Furthermore, the migration rate of HUVECs in each group was observed by wound healing assay after 48 h cultured (n=3). Results: Compared with NG group, the cell viability and eNOS protein phosphorylation level of hBMSC in HG group and the contents of NO, VEGF and IL-8 in the supernatant of cultured medium were decreased (P<0.05). Compared with HG group, the cell viability and eNOS protein phosphorylation level in HG+E2 group and the contents of NO, VEGF and IL-8 in cultured medium supernatant were increased significantly (P<0.05), whereas pre-treatment of hBMSC cells with a Akt inhibitor Triciribine, the above indexes showed reverse changes (P<0.05). Furthermore, compared with HG-CM group, the cell viability and migration ability (P<0.05) of HUVECs in HG+E2-CM group were increased significantly (P<0.05), and the proportion of apoptosis was decreased (P<0.05). While compared with HG+E2-CM group, the cell viability and migration ability of HUVECs in HG+E2+Triciribine-CM group were decreased (P<0.05), and the proportion of apoptosis was increased (P<0.05). Conclusion: Estrogen may promote the secretion of NO, VEGF and IL-8 by activating the Akt/eNOS signaling pathway of hBMSC cells, increase the cell viability and migration ability of HUVECs and inhibit the occurrence of apoptosis, play a protective role against the injury of HUVECs induced by HG condition.

SNHG3 promotes migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the miR-186-5p/ZEB1 axis.

Increasing evidence suggests that the long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. The lncRNA small nucleolar RNA host gene 3 (SNHG3) reportedly acts as an oncogene in hepatocellular carcinoma and colorectal cancer; however, little is known about the biological function and oncogenic mechanisms of SNHG3 in breast cancer. We demonstrated that the expression of SNHG3 was abnormally high in breast cancer tissues and cells, and transgenic expression of SNHG3 promoted the proliferation, migration, and invasion of breast cancer cell lines (MCF-7 and MDA-MB-231). The mean volume of the xenografts from the SNHG3-knockdown MCF-7 cells was lower than that of the control tumor cells. Moreover, the expression of zinc finger E-box binding homeobox 1 (ZEB1) increased after SNHG3 overexpression and vice versa. Overexpression of ZEB1 triggered cellular migration and invasion behaviors. Analysis of the mechanism underlying these effects suggested that SNHG3 is an effective sink for miR-186-5p and modulates ZEB1 repression, conferring an additional level to its post-transcriptional regulation. In conclusion, SNHG3 promotes the migration and invasion of breast cancer cells through miR-186-5p/ZEB1 regulation and the induction of the epithelial to mesenchymal transition, indicating that SNHG3 is a potential treatment target for breast cancer.

Dual antiplatelet therapy reduced stroke risk in transient ischemic attack with positive diffusion weighted imaging.

Dual antiplatelet therapy (DAPT) reduced stroke risk in high-risk transient ischemic attack (TIA) patients assessed by ABCD2 score. Patients with positive diffusion-weighted imaging (DWI) were identified as imaging-based high-risk. The present study aims to investigate whether DAPT could reduce stroke risk in TIA with DWI positive. The study enrolled TIA patients within 72 h of onset from the prospective TIA database of the First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischemic stroke at 90-day. The relationship between DAPT and stroke was analyzed in a cox proportional hazards model. The Kaplan-Meier curves of TIA patients with DAPT and monotherapy were plotted. Total of 661 TIA patients were enrolled, 279 of whom were DWI positive and 281 used DAPT. The 90-day stroke risk was higher in patients used monotherapy than those used DAPT in TIA with positive DWI (23.7% vs. 13.4%, p = 0.029). DAPT was associated with reduced stroke risk in TIA patients with positive DWI (hazard ratio [HR] = 0.54; 95% confidence interval [CI], 0.30-0.97; p = 0.037). However, the benefit didn't exist in TIA patients with negative DWI (HR = 0.43; 95% CI, 0.14-1.33; p = 0.142). Early use of DAPT reduced stroke risk in TIA patients with positive DWI.

Endothelial Progenitor Cells' Classification and Application in Neurological Diseases.

The therapeutic effects of endothelial progenitor cells (EPCs) on ischemic stroke have been extensively studied in recent years. However, the differences in early EPCs and endothelial outgrowth cells (EOCs) are still unclear. Clarifications of their respective properties and specific functioning characteristics contribute to better applications of EPCs in ischemic diseases. In this review, we discuss cellular origin, isolation, culture, surface markers of early EPCs and EOCs and relevant applications in neurological diseases. We conclude that EOCs possess all characteristics of true endothelial progenitors and have potent advantages in EPC-based therapies for ischemic diseases. A number of preclinical and clinical applications of EPCs in neurological diseases are under study. More studies are needed to determine the specific characteristics of EPCs and the relevant mechanisms of EPCs for neurological diseases.

Association of FOXF2 gene polymorphisms with ischemic stroke in Chinese Han population.

Recently, a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with an increased risk of stroke in European populations was identified. However, whether polymorphisms in FOXF2 are also associated with the incidence of ischemic stroke in other populations remains unknown. In this case-control study, 803 Chinese Han patients with ischemic stroke and 803 matched control individuals were enrolled. Four tag SNPs and rs12204590 located in or near FOXF2 were selected, and the associations between genotypes/alleles and ischemic stroke were analyzed. In our study, we did not detect an association between the previously reported locus rs12204590 and ischemic stroke. By the genotype analysis, a novel SNP rs1711972, near FOXF2, was observed to be associated with an increased risk of ischemic stroke(CA genotype, adjusted OR = 1.35; 95% CI, 1.07 to 1.70), but not significantly after Bonferroni corrections for multiple tests. However, in the subgroup analysis, we discovered that rs1711972 was associated with an increased risk of large-artery atherosclerotic stroke in the additive model (P = 0.020; CA genotype, adjusted OR = 1.50; 95%CI, 1.09 to 2.07) and dominant model (P = 0.010; OR = 1.47; 95%CI, 1.09 to 1.99). Collectively, these results indicate that a novel SNP near FOXF2 may influence the risk of large-artery atherosclerotic stroke in Chinese Han population.

PTA wastewater molecular toxicity detected with gene chip.

The purified terephthalic acid (PTA) petrochemical wastewater molecular toxicity detected by use of Mouse Genome 430A 2.0 GeneChip was conducted in this research. The toxic dose to male mice was 0.03 g/(kg x d) of PTA in the wastewater. The mice liver total RNA was isolated as the temple for synthesis of cDNA and then the cDNA as the temple for synthesis of cRNA. Hybridizing the cRNA with the target genes on the gene chip, there were 232 genes expression levels up-regulated and 74 genes down-regulated discovered obviously. The foremost 40 genes for both the highest and the lowest expression levels involved endogenetic steroid and hormone metabolism, immune system, the leukocyte activity and inflammation, detoxification in liver, reproduction and growth hormone, regulation immune factors of anti-tumor and anti-infection and cancer to the mice sampled. The data suggest the PTA wastewater contained over 5 aromatics and their toxicities integrated were much higher than the pure chemical PTA. And the pure chemical PTA toxicities data cannot be used to evaluate the toxicity of the PTA wastewater instead.

Regulation of Hydroxylation and Nitroreduction Pathways during Metabolism of the Neonicotinoid Insecticide Imidacloprid by Pseudomonas putida.

Imidacloprid (IMI) is mainly metabolized via nitroreduction and hydroxylation pathways, which produce different metabolites that are toxic to mammals and insects. However, regulation of IMI metabolic flux between nitroreduction and hydroxylation pathways is still unclear. In this study, Pseudomonas putida was found to metabolize IMI to 5-hydroxy and nitroso IMI and was therefore used for investigating the regulation of IMI metabolic flux. The cell growth time, cosubstrate, dissolved oxygen concentration, and pH showed significant effect on IMI degradation and nitroso and 5-hydroxy IMI formation. Gene cloning and overexpression in Escherichia coli proved that P. putida KT2440 aldehyde oxidase mediated IMI nitroreduction to nitroso IMI, while cytochrome P450 monooxygenase (CYP) failed to improve IMI hydroxylation. Moreover, E. coli cells without CYP could hydroxylate IMI, demonstrating the role of a non-CYP enzyme in IMI hydroxylation. Thus, the present study helps to further understand the environmental fate of IMI and its underlying mechanism.

Purified terephthalic acid wastewater biodegradation and toxicity.

The biodegradation and toxicity of the purified terephthalic acid (PTA) processing wastewater was researched at NJYZ pilot with the fusant strain Fhhh in the carrier activated sludge process (CASP). Sludge loading rate (SLR) for Fhhh to COD of the wastewater was 1.09 d(-1) and to PTA in the wastewater was 0.29 d(-1). The results of bioassay at the pilot and calculation with software Ebis3 showed that the 48h-LC50 (median lethal concentration) to Daphnia magna for the PTA concentration in the wastewater was only 1/10 of that for the chemical PTA. There were 5 kinds of benzoate pollutants and their toxicities existing in the wastewater at least. The toxicity parameter value of the pure chemical PTA cannot be used to predicate the PTA wastewater toxicity. The toxicity of the NJYZ PTA wastewater will be discussed in detail in this paper.

Pilot regulation of MnP-SA for treating PTA wastewater.

In the pilot study of treating the purified terephthalic acid (PTA) wastewater with the functional Strain Fhhh in the carrier activated sludge process (CASP), the ratio of COD: TN: TP and the concentrations of Cu, Mn, Se and Zn were controlled to improve the manganese peroxidase (MnP) levels for increasing the treatment efficiency. When the ratio of COD: TN: TP was 100: 0.36: 0.15 and the concentrations of Cu, Mn, Se and Zn were 0.54, 5.07, 0.00 and 0.08 mg/L, the MnP specific activity (MnP-SA) reached 689 U/L, and the sludge loading rate to COD(SLRC) was 1.09 d(-l), which was 4--7 fold of that in other processes reported. The data indicated that improving MnP level could enhance the degradability of Fhhh. And the potentials of Fhhh and CASP will be also discussed in this paper.