Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of clinically aggressive tumors with high risk of recurrence and metastasis. Current pharmacological treatment options remain largely limited to chemotherapy. Despite promising results, the efficacy of immunotherapy and chemo-immunotherapy in TNBC remains limited. There is strong evidence supporting the involvement of Notch signaling in TNBC progression. Expression of Notch1 and its ligand Jagged1 correlate with poor prognosis. Notch inhibitors, including g-secretase inhibitors (GSIs), are quite effective in preclinical models of TNBC. However, the success of GSIs in clinical trials has been limited by their intestinal toxicity and potential for adverse immunological effects, since Notch plays key roles in T-cell activation, including CD8 T-cells in tumors. Our overarching goal is to replace GSIs with agents that lack their systemic toxicity and ideally, do not affect tumor immunity. We identified sulindac sulfide (SS), the active metabolite of FDA-approved NSAID sulindac, as a potential candidate to replace GSIs. Methods: We investigated the pharmacological and immunotherapeutic properties of SS in TNBC models in vitro, ex-vivo and in vivo. Results: We confirmed that SS, a known γ-secretase modulator (GSM), inhibits Notch1 cleavage in TNBC cells. SS significantly inhibited mammosphere growth in all human and murine TNBC models tested. In a transplantable mouse TNBC tumor model (C0321), SS had remarkable single-agent anti-tumor activity and eliminated Notch1 protein expression in tumors. Importantly, SS did not inhibit Notch cleavage in T- cells, and the anti-tumor effects of SS were significantly enhanced when combined with a-PD1 immunotherapy in our TNBC organoids and in vivo. Discussion: Our data support further investigation of SS for the treatment of TNBC, in conjunction with chemo- or -chemo-immunotherapy. Repurposing an FDA-approved, safe agent for the treatment of TNBC may be a cost-effective, rapidly deployable therapeutic option for a patient population in need of more effective therapies.

Impact of temperature and biomass augmentation on biosulfur-driven autotrophic denitrification in membrane bioreactors treating real nitrate-contaminated groundwater.

Nitrate (NO3-) contamination of groundwater is a major health concern worldwide as it can lead to serious illnesses such as methemoglobinemia and cancer. Autotrophic denitrification is a smart approach for treating groundwater, being typically organic-deficient. Lately, biogenic sulfur (S0bio) has emerged as a sustainable, free, and high-efficiency substrate to fuel membrane bioreactors (MBRs) treating contaminated groundwater. However, the effects of moderate temperature and biomass concentration on the performance and fouling of the S0bio-fed MBR were not investigated previously. This study shows that biomass levels of ~1 g MLVSS/L limit membrane fouling but also denitrification efficiency. Biomass augmentation up to 3 g MLVSS/L enhanced denitrification but worsened fouling due to increase of extracellular polymeric substance (EPS) levels in the bulk liquid. Temperature decrease from 30 °C to 20 °C halved denitrification efficiency, which could be partially recovered through bioaugmentation. The mechanisms affected by temperature decrease, practical applications, and future research needs were discussed.

Targeting the Cbl-b-Notch1 axis as a novel immunotherapeutic strategy to boost CD8+ T-cell responses.

A critical feature of cancer is the ability to induce immunosuppression and evade immune responses. Tumor-induced immunosuppression diminishes the effectiveness of endogenous immune responses and decreases the efficacy of cancer immunotherapy. In this study, we describe a new immunosuppressive pathway in which adenosine promotes Casitas B-lineage lymphoma b (Cbl-b)-mediated Notch1 degradation, causing suppression of CD8+ T-cells effector functions. Genetic knockout and pharmacological inhibition of Cbl-b prevents Notch1 degradation in response to adenosine and reactivates its signaling. Reactivation of Notch1 results in enhanced CD8+ T-cell effector functions, anti-cancer response and resistance to immunosuppression. Our work provides evidence that targeting the Cbl-b-Notch1 axis is a novel promising strategy for cancer immunotherapy.

Sequential sulfur-based denitrification/denitritation and nanofiltration processes for drinking water treatment.

Efficient and cost-effective solutions for nitrogen removal are necessary to ensure the availability of safe drinking water. This study proposes a combined treatment for nitrogen-contaminated groundwater by sequential autotrophic nitrogen removal in a sulfur-packed bed reactor (SPBR) and excess sulfate rejection via nanofiltration (NF). Autotrophic nitrogen removal in the SPBR was investigated under both denitrification and denitritation conditions under different NO3- and NO2- loading rates (LRs) and feeding strategies (NO3- only, NO2- only, or both NO3- and NO2- in the feed). Batch activity tests were carried out during SPBR operation to evaluate the effect of different feeding conditions on nitrogen removal activity by the SPBR biofilm. Bacteria responsible for nitrogen removal in the bioreactor were identified via Illumina sequencing. Dead-end filtration tests were performed with NF membranes to investigate the elimination of excess sulfate from the SPBR effluent. This study demonstrates that the combined process results in effective groundwater treatment and evidences that an adequately high nitrogen LR should be maintained to avoid the generation of excess sulfide.

Correction: Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor.

[This corrects the article DOI: 10.1371/journal.pone.0226464.].

Dual inhibition of MEK1/2 and MEK5 suppresses the EMT/migration axis in triple-negative breast cancer through FRA-1 regulation.

Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. Constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has been linked to chemoresistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT) when cells adopt a motile and invasive phenotype through loss of epithelial markers (CDH1), and acquisition of mesenchymal markers (VIM, CDH2). Although MAPK/ERK1/2 kinase inhibitors (MEKi) are useful antitumor agents in a clinical setting, including the Food and Drug Administration (FDA)-approved MEK1,2 dual inhibitors cobimetinib and trametinib, there are limitations to their clinical utility, primarily adaptation of the BRAF pathway and ocular toxicities. The MEK5 (HGNC: MAP2K5) pathway has important roles in metastatic progression of various cancer types, including those of the prostate, colon, bone and breast, and elevated levels of ERK5 expression in breast carcinomas are linked to a worse prognoses in TNBC patients. The purpose of this study is to explore MEK5 regulation of the EMT axis and to evaluate a novel pan-MEK inhibitor on clinically aggressive TNBC cells. Our results show a distinction between the MEK1/2 and MEK5 cascades in maintenance of the mesenchymal phenotype, suggesting that the MEK5 pathway may be necessary and sufficient in EMT regulation while MEK1/2 signaling further sustains the mesenchymal state of TNBC cells. Furthermore, additive effects on MET induction are evident through the inhibition of both MEK1/2 and MEK5. Taken together, these data demonstrate the need for a better understanding of the individual roles of MEK1/2 and MEK5 signaling in breast cancer and provide a rationale for the combined targeting of these pathways to circumvent compensatory signaling and subsequent therapeutic resistance.

Diverse and converging roles of ERK1/2 and ERK5 pathways on mesenchymal to epithelial transition in breast cancer.

The epithelial to mesenchymal transition (EMT) is characterized by a loss of cell polarity, a decrease in the epithelial cell marker E-cadherin, and an increase in mesenchymal markers including the zinc-finger E-box binding homeobox (ZEB1). The EMT is also associated with an increase in cell migration and anchorage-independent growth. Induction of a reversal of the EMT, a mesenchymal to epithelial transition (MET), is an emerging strategy being explored to attenuate the metastatic potential of aggressive cancer types, such as triple-negative breast cancers (TNBCs) and tamoxifen-resistant (TAMR) ER-positive breast cancers, which have a mesenchymal phenotype. Patients with these aggressive cancers have poor prognoses, quick relapse, and resistance to most chemotherapeutic drugs. Overexpression of extracellular signal-regulated kinase (ERK) 1/2 and ERK5 is associated with poor patient survival in breast cancer. Moreover, TNBC and tamoxifen resistant cancers are unresponsive to most targeted clinical therapies and there is a dire need for alternative therapies. In the current study, we found that MAPK3, MAPK1, and MAPK7 gene expression correlated with EMT markers and poor overall survival in breast cancer patients using publicly available datasets. The effect of ERK1/2 and ERK5 pathway inhibition on MET was evaluated in MDA-MB-231, BT-549 TNBC cells, and tamoxifen-resistant MCF-7 breast cancer cells. Moreover, TU-BcX-4IC patient-derived primary TNBC cells were included to enhance the translational relevance of our study. We evaluated the effect of pharmacological inhibitors and lentivirus-induced activation or inhibition of the MEK1/2-ERK1/2 and MEK5-ERK5 pathways on cell morphology, E-cadherin, vimentin and ZEB1 expression. Additionally, the effects of pharmacological inhibition of trametinib and XMD8-92 on nuclear localization of ERK1/2 and ERK5, cell migration, proliferation, and spheroid formation were evaluated. Novel compounds that target the MEK1/2 and MEK5 pathways were used in combination with the AKT inhibitor ipatasertib to understand cell-specific responses to kinase inhibition. The results from this study will aid in the design of innovative therapeutic strategies that target cancer metastases.

Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.

Extracellular signal-regulated kinase (ERK5) is an essential regulator of cancer progression, tumor relapse, and poor patient survival. Epithelial to mesenchymal transition (EMT) is a complex oncogenic process, which drives cell invasion, stemness, and metastases. Activators of ERK5, including mitogen-activated protein kinase 5 (MEK5), tumor necrosis factor α (TNF-α), and transforming growth factor-ß (TGF-ß), are known to induce EMT and metastases in breast, lung, colorectal, and other cancers. Several downstream targets of the ERK5 pathway, such as myocyte-specific enhancer factor 2c (MEF2C), activator protein-1 (AP-1), focal adhesion kinase (FAK), and c-Myc, play a critical role in the regulation of EMT transcription factors SNAIL, SLUG, and ß-catenin. Moreover, ERK5 activation increases the release of extracellular matrix metalloproteinases (MMPs), facilitating breakdown of the extracellular matrix (ECM) and local tumor invasion. Targeting the ERK5 signaling pathway using small molecule inhibitors, microRNAs, and knockdown approaches decreases EMT, cell invasion, and metastases via several mechanisms. The focus of the current review is to highlight the mechanisms which are known to mediate cancer EMT via ERK5 signaling. Several therapeutic approaches that can be undertaken to target the ERK5 pathway and inhibit or reverse EMT and metastases are discussed.

Self-forming dynamic membrane bioreactor for textile industry wastewater treatment.

The robustness of anaerobic dynamic membrane bioreactor (AnDMBR) for synthetic textile wastewater treatment was investigated. Textile wastewater may contain high concentrations of NaCl and sulfate, hence their impact on the AnDMBR performance was investigated in detail. A dynamic membrane was formed on a 20-µm pore sized nylon support layer at a constant flux of around 8 LMH. In the absence of sulfate addition, total and filtered (soluble) COD averaged 96 ± 49 mg/L (91% removal) and 75 ± 35 mg/L (93% removal), respectively. Sulfate addition increased total COD in the permeate to 222 ± 68 mg/L (79% removal). Average SS concentration was lower than 30 mg/L in the permeate although its concentration in the bioreactor reached 10 g/L. Throughout the AnDMBR operation dye removal averaged >97%. Sludge filterability, which was assessed by specific resistance to filtration, supernatant filtration, capillary suction time and viscosity, decreased after sulfate addition. Organic and inorganic matters in the dynamic layer were characterized by SEM-EDS and FTIR analyses.

Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor.

Metaplastic breast carcinoma (MBC) is a clinically aggressive and rare subtype of breast cancer, with similar features to basal-like breast cancers. Due to rapid growth rates and characteristic heterogeneity, MBC is often unresponsive to standard chemotherapies; and novel targeted therapeutic discovery is urgently needed. Histone deacetylase inhibitors (DACi) suppress tumor growth and metastasis through regulation of the epithelial-to-mesenchymal transition axis in various cancers, including basal-like breast cancers. We utilized a new MBC patient-derived xenograft (PDX) to examine the effect of DACi therapy on MBC. Cell morphology, cell cycle-associated gene expressions, transwell migration, and metastasis were evaluated in patient-derived cells and tumors after treatment with romidepsin and panobinostat. Derivations of our PDX model, including cells, spheres, organoids, explants, and in vivo implanted tumors were treated. Finally, we tested the effects of combining DACi with approved chemotherapeutics on relative cell biomass. DACi significantly suppressed the total number of lung metastasis in vivo using our PDX model, suggesting a role for DACi in preventing circulating tumor cells from seeding distal tissue sites. These data were supported by our findings that DACi reduced cell migration, populations, and expression of mesenchymal-associated genes. While DACi treatment did affect cell cycle-regulating genes in vitro, tumor growth was not affected compared to controls. Importantly, gene expression results varied depending on the cellular or tumor system used, emphasizing the importance of using multiple derivations of cancer models in preclinical therapeutic discovery research. Furthermore, DACi sensitized and produced a synergistic effect with approved oncology therapeutics on inherently resistant MBC. This study introduced a role for DACi in suppressing the migratory and mesenchymal phenotype of MBC cells through regulation of the epithelial-mesenchymal transition axis and suppression of the CTC population. Preliminary evidence that DACi treatment in combination with MEK1/2 inhibitors exerts a synergistic effect on MBC cells was also demonstrated.

A novel screening approach comparing kinase activity of small molecule inhibitors with similar molecular structures and distinct biologic effects in triple-negative breast cancer to identify targetable signaling pathways.

Breast cancer affects women globally; the majority of breast cancer-related mortalities are due to metastasis. Acquisition of a mesenchymal phenotype has been implicated in the progression of breast cancer cells to an invasive, metastatic state. Triple-negative breast cancer (TNBC) subtypes have high rates of metastases, recurrence, and have poorer prognoses compared to other breast cancer types, partially due to lack of commonly targeted receptors. Kinases have diverse and pivotal functions in metastasis in TNBC, and discovery of new kinase targets for TNBC is warranted. We previously used a screening approach to identify intermediate-synthesis nonpotent, nonselective small-molecule inhibitors from the Published Kinase Inhibitor Set that reversed the mesenchymal phenotype in TNBC cells. Two of these inhibitors (GSK346294A and GSK448459A) are structurally similar, but have unique kinase activity profiles and exhibited differential biologic effects on TNBC cells, specifically on epithelial-to-mesenchymal transition (EMT). Here, we further interrogate these effects and compare activity of these inhibitors on transwell migration, gene (qRT-PCR) and protein (western blot) expressions, and cancer stem cell-like behavior. We incorporated translational patient-derived xenograft models in these studies, and we focused on the lead inhibitor hit, GSK346294A, to demonstrate the utility of our comparative analysis as a screening modality to identify novel kinase targets and signaling pathways to pursue in TNBC. This study introduces a new method for discovering novel kinase targets that reverse the EMT phenotype; this screening approach can be applied to all cancer types and is not limited to breast cancer.

Process optimization and filtration performance of an anaerobic dynamic membrane bioreactor treating textile wastewaters.

The study aimed at investigating the performance of anaerobic dynamic MBR (AnDMBR) for the treatment of synthetic textile wastewater. A laboratory scale anaerobic bioreactor was operated to test nylon mesh support materials with different pore sizes (20 µm, 53 µm and 100 µm). The performances of the AnDMBR were evaluated with a stimulated wastewater containing 1,000 mg.L-1 COD and 100 mg.L-1 dye (Remazol Brilliant Violet 5R). To develop an effective dynamic cake layer on the support material, different operational strategies, i.e. high flux, continuous and intermittently biogas recycle were studied for process optimization and increase the filtration performances. Initially, the bioreactor was operated under continuous biogas recycle. Under this operation strategy, the cake layer was not formed, then intermittent biogas recycle was applied to improve the development of dynamic layer. Effluent SS decreased below 20 mg-SS.L-1 for all the tested different pore sized supports after the development of the cake layer. Almost complete color (>99%) and high COD removal efficiencies (95-97%) were observed. For all the three supports, the bioreactor was operated at fluxes of 5-15 L.(m2.h)-1 (LMH), which was quite high compared to conventional AnMBRs equipped with micro/ultra-filtration membranes. In order to better understand the formation and its structure, detailed cake layer characterization analyses were conducted with scanning electron microscopy (SEM), SEM coupled Energy Dispersive X-ray Spectroscopy (EDS) and inductively coupled plasma-optical emission spectrometer (ICP). Provided the formation of the cake layer, the comparable flux and removal performances with AnMBRs for all three tested support materials were possible.

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer.

Conventional mitogen-activated protein kinase (MAPK) family members regulate diverse cellular processes involved in tumor initiation and progression, yet the role of ERK5 in cancer biology is not fully understood. Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. ERK5 signaling contributes to drug resistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT). More recently a role for ERK5 in regulation of the extracellular matrix (ECM) has been proposed, and here we investigated the necessity of ERK5 in TNBC tumor formation. Depletion of ERK5 expression using the CRISPR/Cas9 system in MDA-MB-231 and Hs-578T cells resulted in loss of mesenchymal features, as observed through gene expression profile and cell morphology, and suppressed TNBC cell migration. In vivo xenograft experiments revealed ERK5 knockout disrupted tumor growth kinetics, which was restored using high concentration Matrigel™ and ERK5-ko reduced expression of the angiogenesis marker CD31. These findings implicated a role for ERK5 in the extracellular matrix (ECM) and matrix integrity. RNA-sequencing analyses demonstrated downregulation of matrix-associated genes, integrins, and pro-angiogenic factors in ERK5-ko cells. Tissue decellularization combined with cryo-SEM and interrogation of biomechanical properties revealed that ERK5-ko resulted in loss of key ECM fiber alignment and mechanosensing capabilities in breast cancer xenografts compared to parental wild-type cells. In this study, we identified a novel role for ERK5 in tumor growth kinetics through modulation of the ECM and angiogenesis axis in breast cancer.

Comparison of biogenic and chemical sulfur as electron donors for autotrophic denitrification in sulfur-fed membrane bioreactor (SMBR).

Two sulfur-oxidizing membrane bioreactors (SMBRs) performing autotrophic denitrification at different HRTs (6-26 h), one supplemented with biogenic elemental sulfur (S0bio) and the other with chemically-synthesized elemental sulfur (S0chem), were compared in terms of nitrate reduction rates, impact on membrane filtration and microbial community composition. Complete denitrification with higher rates (up to 286 mg N-NO3-/L d) was observed in the SMBR supplemented with S0bio (SMBRbio), while nitrate was never completely reduced in the SMBR fed with S0chem (SMBRchem). Trans membrane pressure was higher for SMBRbio due to smaller particle size and colloidal properties of S0bio. Microbial communities in the two SMBRs were similar and dominated by Proteobacteria, with Pleomorphomonas and Thermomonas being the most abundant genera in both bioreactors. This study reveals that S0bio can be effectively used for nitrate removal in autotrophic denitrifying MBRs and results in higher nitrate reduction rates compared to S0chem.

Notch Signaling Regulates Mitochondrial Metabolism and NF-κB Activity in Triple-Negative Breast Cancer Cells via IKKα-Dependent Non-canonical Pathways.

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as a novel patient-derived model. We demonstrate that exposure of TNBC cells to recombinant Notch ligand Jagged1 leads to rapid AKT phosphorylation in a Notch1-dependent but RBP-Jκ independent fashion. This requires mTOR and IKKα. Jagged1 also stimulates mitochondrial respiration and fermentation in an AKT- and IKK-dependent fashion. Notch1 co-localizes with mitochondria in TNBC cells. Pharmacological inhibition of Notch cleavage by gamma secretase inhibitor PF-03084014 in combination with AKT inhibitor MK-2206 or IKK-targeted NF-κB inhibitor Bay11-7082 blocks secondary mammosphere formation from sorted CD90hi or CD44+CD24low (CSCs) cells. A TNBC patient-derived model gave comparable results. Besides mitochondrial oxidative metabolism, Jagged1 also triggers nuclear, NF-κB-dependent transcription of anti-apoptotic gene cIAP-2. This requires recruitment of Notch1, IKKα and NF-κB to the cIAP-2 promoter. Our observations support a model where Jagged1 triggers IKKα-dependent, mitochondrial and nuclear Notch1 signals that stimulate AKT phosphorylation, oxidative metabolism and transcription of survival genes in PTEN wild-type TNBC cells. These data suggest that combination treatments targeting the intersection of the Notch, AKT and NF-κB pathways have potential therapeutic applications against CSCs in TNBC cases with Notch1 and wild-type PTEN expression.

Notch Signaling in Myeloid Cells as a Regulator of Tumor Immune Responses.

Cancer immunotherapy, which stimulates or augments host immune responses to treat malignancies, is the latest development in the rapidly advancing field of cancer immunology. The basic principles of immunotherapies are either to enhance the functions of specific components of the immune system or to neutralize immune-suppressive signals produced by cancer cells or tumor microenvironment cells. When successful, these approaches translate into long-term survival for patients. However, durable responses are only seen in a subset of patients and so far, only in some cancer types. As for other cancer treatments, resistance to immunotherapy can also develop. Numerous research groups are trying to understand why immunotherapy is effective in some patients but not others and to develop strategies to enhance the effectiveness of immunotherapy. The Notch signaling pathway is involved in many aspects of tumor biology, from angiogenesis to cancer stem cell maintenance to tumor immunity. The role of Notch in the development and modulation of the immune response is complex, involving an intricate crosstalk between antigen-presenting cells, T-cell subpopulations, cancer cells, and other components of the tumor microenvironment. Elegant studies have shown that Notch is a central mediator of tumor-induced T-cell anergy and that activation of Notch1 in CD8 T-cells enhances cancer immunotherapy. Tumor-infiltrating myeloid cells, including myeloid-derived suppressor cells, altered dendritic cells, and tumor-associated macrophages along with regulatory T cells, are major obstacles to the development of successful cancer immunotherapies. In this article, we focus on the roles of Notch signaling in modulating tumor-infiltrating myeloid cells and discuss implications for therapeutic strategies that modulate Notch signaling to enhance cancer immunotherapy.

An Overview of Electron Acceptors in Microbial Fuel Cells.

Microbial fuel cells (MFC) have recently received increasing attention due to their promising potential in sustainable wastewater treatment and contaminant removal. In general, contaminants can be removed either as an electron donor via microbial catalyzed oxidization at the anode or removed at the cathode as electron acceptors through reduction. Some contaminants can also function as electron mediators at the anode or cathode. While previous studies have done a thorough assessment of electron donors, cathodic electron acceptors and mediators have not been as well described. Oxygen is widely used as an electron acceptor due to its high oxidation potential and ready availability. Recent studies, however, have begun to assess the use of different electron acceptors because of the (1) diversity of redox potential, (2) needs of alternative and more efficient cathode reaction, and (3) expanding of MFC based technologies in different areas. The aim of this review was to evaluate the performance and applicability of various electron acceptors and mediators used in MFCs. This review also evaluated the corresponding performance, advantages and disadvantages, and future potential applications of select electron acceptors (e.g., nitrate, iron, copper, perchlorate) and mediators.

A novel elemental sulfur-based mixotrophic denitrifying membrane bioreactor for simultaneous Cr(VI) and nitrate reduction.

This study aims at investigating the simultaneous nitrate and chromate reduction by combining the advantages of sulfur-based autotrophic denitrification, heterotrophic denitrification and membrane bioreactor (MBR) technologies. A laboratory-scale MBR equipped with hydrophilic flat sheet polyethersulfone (PES) membranes (0.45µm) was used to evaluate the performance of mixotrophic denitrification at varying nitrate and Cr(VI) concentrations. Methanol was supplied at C/N (mg methanol/mg NO3--N) ratio of 1.33. In the absence of Cr(VI), almost complete denitrification of 50mg/L NO3--N was obtained and the methanol requirement (3.60±0.9mg COD/(mg NO3--N)) for heterotrophic denitrifiers, was quite close to the theoretical value (3.7mg COD/(mg NO3--N)). Around 54% of the influent nitrate was denitrified by heterotrophs and the rest (56%) was denitrified by autotrophic sulfur oxidizers. The effluent sulfate averaged around 200mg/L, which was below than the theoretical sulfate concentration if autotrophic denitrification process was used alone. Autotrophic denitrification activity completely ceased at 5mg/L Cr(VI), but heterotrophic denitrification did not show any inhibition. Almost complete chromate and nitrate reduction was observed at 1mg/L Cr(VI). MBR was operated for around 200days and a weekly physical membrane cleaning was enough at a flux of 15 LMH.

Heterotrophic-autotrophic sequential system for reductive nitrate and perchlorate removal.

Nitrate and perchlorate were identified as significant water contaminants all over the world. This study aims at evaluating the performances of the heterotrophic-autotrophic sequential denitrification process for reductive nitrate and perchlorate removal from drinking water. The reduced nitrate concentration in the heterotrophic reactor increased with increasing methanol concentrations and the remaining nitrate/nitrite was further removed in the following autotrophic denitrifying process. The performances of the sequential process were studied under varying nitrate loads of [Formula: see text] at a fixed hydraulic retention time of 2 h. The C/N ratio in the heterotrophic reactor varied between 1.24 and 2.77 throughout the study. Nitrate and perchlorate reduced completely with maximum initial concentrations of [Formula: see text] and 1000 µg/L, respectively. The maximum denitrification rate for the heterotrophic reactor was [Formula: see text] when the bioreactor was fed with [Formula: see text] and 277 mg/L methanol. For the autotrophic reactor, the highest denitrification rate was [Formula: see text] in the first period when the heterotrophic reactor performance was low. Perchlorate reduction was initiated in the heterotrophic reactor, but completed in the following autotrophic process. Effluent sulphate concentration was below the drinking water standard level of 250 mg/L and pH was in the neutral level.

Performances of anaerobic and aerobic membrane bioreactors for the treatment of synthetic textile wastewater.

This study aims at comparatively evaluating anaerobic and aerobic MBRs for the treatment of azo-dye containing synthetic wastewater. Also, the filtration performances of AnMBR and AeMBR were compared under similar operating conditions. In both MBRs, high COD removal efficiencies were observed. Although almost complete color removal was observed in AnMBR, only partial (30-50%) color removal was achieved in AeMBR. AnMBR was successfully operated up to 9 L/(m(2)h) (LMH) and no chemical cleaning was required at 4.5 LMH for around 50 days. AeMBR was operated successfully up to 20 LMH. The filtration resistance of AnMBR was generally higher compared to AeMBR although reversible fouling rates were comparable. In both MBRs, offline chemical cleaning with NaOCl and sulfuric acid almost completely removed irreversible fouling and the resistances of chemically cleaned membranes were close to those of new membranes.