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关键词： definitive endoderm (DE) differentiation   human pluripotent stem cells (hPSCs)   pluripotent expansion   stirred suspension bioreactor (SSB)   xeno-free  

摘要： Scalable processes are requisite for the robust biomanufacturing of human pluripotent stem cell (hPSC)-derived therapeutics. Toward this end, we demonstrate the xeno-free expansion and directed differentiation of human embryonic and induced pluripotent stem cells to definitive endoderm (DE) in a controlled stirred suspension bioreactor (SSB). Based on previous work on converting hPSCs to insulin-producing progeny, differentiation of two hPSC lines was optimized in planar cultures yielding up to 87% FOXA2(+)/SOX17(+) cells. Next, hPSCs were propagated in an SSB with controlled pH and dissolved oxygen. Cultures displayed a 10- to 12-fold increase in cell number over 5-6 days with the maintenance of pluripotency (>85% OCT4(+)) and viability (>85%). For differentiation, SSB cultures yielded up to 89% FOXA2(+)/SOX17(+) cells or similar to 8 DE cells per seeded hPSC. Specification to DE cell fate was consistently more efficient in the bioreactor compared to planar cultures. Hence, a tunable strategy is established that is suitable for the xeno-free manufacturing of DE cells from different hPSC lines in scalable SSBs. This study advances bioprocess development for producing a wide gamut of human DE cell-derived therapeutics.

摘要： The bone marrow microenvironment contains cellular niches that maintain the pool of hematopoietic stem and progenitor cells and support hematopoietic maturation. Malignant hematopoietic cells also co-opt normal cellular interactions to promote their own growth and evade therapy. In vivo systems used to study human hematopoiesis have been developed through transplantation into immunodeficient mouse models. However, incomplete cross-compatibility between the murine stroma and transplanted human hematopoietic cells limits the rate of engraftment and the study of relevant interactions. To supplement in vivo xenotransplantation models, complementary strategies have recently been developed, including the use of three-dimensional human bone marrow organoids in vivo, generated from bone marrow stromal cells seeded onto osteoinductive scaffolds, as well as the use of ex vivo bioreactor models. These topics were the focus of the Spring 2020 International Society for Experimental Hematology New Investigator webinar. We review here the latest advances in generating humanized hematopoietic organoids and how they allow for the study of novel microenvironmental interactions. (c) 2020 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

关键词： Ibuprofen (IBU)   Forward osmosis membrane bioreactor (FOMBR)   Degradation mechanism   Microbial community structure  

摘要： Ibuprofen (IBU) is a non-steroidal drug that is classified as a trace organic compound (TrOC). A forward osmosis membrane bioreactor (FOMBR) has traditionally been a favored technology for wastewater treatment. In this study, the IBU degradation mechanism was clarified using an FOMBR. The results indicated that the average removal efficiencies of contaminants were greater than 96.32%. The ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) results demonstrated that there were 10 intermediates and 5 possible pathways during the IBU degradation. Decarboxylation and hydroxylation may be the primary pathways of IBU degradation. The microbial results illustrated that Proteobacteria was dominant and of utmost importance in the degradation process. Thauera and Azoarcus were the dominant genera that participated in contaminant degradation.

关键词： Sequencing batch and intermittent air-lift bioreactor (SBIAB)   Piggery wastewater   Nutrients removal   Functional microbes  

摘要： In this study, a sequencing batch and intermittent air-lift bioreactor (SBIAB) was evaluated under the three independent variables to treat raw piggery wastewater. The effects of hydraulic retention time (HRT), air flow rate and sludge retention time (SRT) on the nutrients removal of SBIAB were researched. The optimum values of HRT, air flow rate and SRT were 8 d, 2 l/min and 20 d, respectively. Meanwhile, the removal rates of chemical oxygen demand (COD), NH4+-N, total nitrogen (TN) and total phosphorus (TP) were up to 89.5%, 93.5%, 61.1% and 57.3%, respectively. Generally, the nutrients removal performance could be enhanced with increasing HRT from 6 to 10 d, while it was inhibited at air flow rate of 3 l/min. Higher air flow rate caused the alkaline pH and high free ammonia concentration, which imposed restrictions on the process of wastewater treatment. In the SBIAB, a coupling of aerobic/anoxic/anaerobic zone was formed according to the changes of oxidation-reduction potential (ORP) values at the optimum condition. Microbial community structure analysis indicated that the functional microbes including Brachymonas, Prokaryote, Giesbergeria, Comamonadaceae bacterium, Clostridiales bacterium, Comamonas, Tissierella, Aequorivita were enriched in the SBIAB, which played a significant role in the removal of complex organics and nitrogen.

关键词： Biofilm development   Starvation condition   Early biofilm   Wastewater treatment  

摘要： Biofilm development on the membrane surface is one of the main reasons for membrane fouling in membrane bioreactors (MBRs) and it is a big problem for their stable operation. Precise information on the microbial community composition of the biofilm is needed for a better understanding of biofilm development. However, there have been limited investigations of the relationship between the biofilm formation process and the microbial community of activated sludge and biofilm in MBRs treating real sewage. In this study, relationships between the microbial community structure of biofilm and activated sludge at each biofilm formation stage were investigated and biofilm growth was elucidated by nondestructive observations. Two anoxic/oxic MBRs were operated and membrane fouling was induced. Permeability rapidly decreased in both reactors and live cell microcolonies were formed on dead cell conditioning film on the membrane surface. Principal component analysis based on 16S rRNA gene sequences showed that the biofilm microbial community changed significantly from middle stage to mature biofilm when compared with that of activated sludge. The abundance of specific bacteria, such as unclassified Neisseriaceae, increased in middle-stage biofilm and the diversity indexes of middle-stage biofilm were lower than those of mature biofilm and activated sludge. These results suggested that the presence of specific bacteria with colonization ability played a crucial role in biofilm formation. Strategies are needed to target membrane fouling mitigation during early- and middle-stage biofilm formation to reduce MBR membrane fouling.

关键词： Soybean hulls   Enzymes   Yarrowia lipolytica   Carbon source supplementation   Temperature monitoring   Scale-up  

摘要： Solid-state fermentation (SSF) with Yarrowia lipolytica requires appropriate medium supplementation and bioreactor configuration for efficient lipase production, which are related to the temperature profile due to the heat release by the metabolic activity and the heat removal mechanisms of the bioreactor. Thus, we evaluated supplementation with complex medium (CM) and defined medium (DM) for lipase production in tray and insulated packed-bed bioreactors (PBB), also assessing protease production. The media were composed of yeast extract (Y), bactopeptone (P) or diammonium phosphate (N), and glucose (D) or soybean oil (0). Lipase activities in tray bioreactors were, in general, higher in CM than in DM, reaching 32 U g(-1) when supplemented with concentrated YPO medium. Supplementation with YPO in the PBB resulted in maximal temperatures of 35 degrees C, with axial and radial temperature differences of up to 5.3 degrees C and 2.1 degrees C, respectively. In this case, the PBB gave 58 % higher lipase yield than the tray, while in the presence of mixed-carbon source (YPDO), the yield was 47 % lower, suggesting that the carbon source is important for SSF scaling-up and the temperature increase was responsible for changes in the use of the soybean oil and in protease secretion by this yeast.

关键词： Model calibration   Sensitivity analysis Elsevier   Dissolved oxygen control   Sliding window optimization  

摘要： The paper presents a novel model calibration and validation strategy of membrane bioreactor (MBR) for wastewater treatment. The approach is based on a dynamic model of the activated sludge process and it consists simultaneously on estimating the model's parameters and computing the dissolved oxygen control input. Activated sludge model No. 1 (ASM1) has been widely used to describe the biological process of activated sludge processes. However, most system states and parameters within ASM1 are not easily obtained, hence not applicable for model calibration and validation. In this work, a reduced-order model presented herein serves as a tool for predicting the dynamic behavior of the MBR plant. The model contains only 4 measurable states, where 13 parameters need to be identified. To reduce the complexity of the calibration, the static sensitivity analysis is performed to select the sensitive parameters. The selected parameters are identified based on directly measurable real-time data obtained from the plant. In addition, the dissolved oxygen is also maintained at a certain level to mimic the real-time control behavior. Model calibration is achieved based on a sliding window optimization problem, which searches for the optimal parameters set and control variables during each identification cycle. Different datasets sampled for the same MBR plant have been used for model validation. Both calibration and validation results are evaluated by several performance indexes, which indicates an acceptable correspondence with the experimental data. The developed model can be employed for process state estimation and control purpose as well as design issues for MBR systems. (c) 2020 Elsevier Ltd. All rights reserved.

关键词： Human medicine   Biological imbalance   Sustainability   Membrane technology  

摘要： Pharmaceutical compounds such antibiotics, anti-inflammatories, psychotropics, human drugs, hormones, anticonvulsants, antidepressants, veterinary drugs and steroids occur widely in wastewater and drinking water. This pollution by active compounds and their metabolites is expected to increase with rising global population. Therefore, advanced monitoring and remediation techniques are needed. Here we review analytical and removal techniques for pharmaceuticals. Techniques focus on titrimetric, electrochemical, chromatographic and electrophoresis for analysis, and on membrane bioreactors for removal.

关键词： fouling   influent wastewater   membrane bioreactor   modeling   planktonic bacteria  

摘要： Membrane bioreactors (MBRs) for wastewater treatment show great potentials in the sustainable development of urban environments. However, fouling of membranes remains the largest challenge of MBR technology. Dissolved extracellular polymeric substances (EPS) are often assumed be the main foulant in MBRs. However, single bacterial cells are often erroneously measured as EPS in traditional spectrophotometric analysis of EPS in activated sludge, so we hypothesized that single cells in many cases could be the true foulants in MBRs for wastewater treatment. To study this, raw MBR sludge and sludge supernatant with varying concentrations of planktonic cells were filtered on microfiltration (MF) membranes, and we found a direct correlation between the cell count and rate of flux decline. Addition of planktonic cells to fresh MBR sludge dramatically increased the flux decline. The identity of the most abundant planktonic cells in a full-scale MBR water resource recovery facility was determined by DNA fingerprinting. Many of these genera are known to be abundant in influent wastewater suggesting that the influent bacterial cells may have a direct effect on the fouling propensity in MBR systems. This new knowledge may lead to new anti-fouling strategies targeting incoming planktonic bacteria from the wastewater feed. Practitioner points Planktonic cells constituted up to 60% of the total protein content of "soluble extracellular polymeric substances" in membrane bioreactor sludge. Planktonic cells are hidden under a surrogate concentration of extracellular polymeric substances which is often associated with fouling. Membrane fouling rate is directly proportional to amount of free planktonic cells suspended in sludge. Several influent bacterial genera are enriched in the water phase of membrane bioreactor sludge. Removing these may mitigate fouling.

关键词： Solid-phase denitrification   Stable isotope   Microbial community   Functional gene   RAS  

摘要： In this research, a solid-phase denitrification reactor (SPDR) packed with corrugated paperboard was introduced into the recirculating aquaculture system (RAS) of Litopenaeus vannamei for nitrate removal. Results showed that 82.88% of the nitrogen was removed from the culture water with the denitrification rate of 0.74 mg L-1 .d(-1) and the concentration of nitrate was controlled at 2.31 +/- 1.00 mg L-1. High throughput sequencing analysis showed that the corrugated paperboard was degraded by Lachnospiraceae, Saprospiraceae, Exiguobacterium, Mesoflavibacter, etc. to provide carbon source for denitrifying bacteria, including Rhizobiaceae, Rhodobacteraceae, Bacillus, Nitratireductor, Sphingobium, Marinicella, Desulfovibrio, Marinobacter, and Labrenzia. The abundance of the functional genes amoA, nirK, and nosZ indicated that nitrogen can be efficiently converted into N-2 in the SPDR.