Comparative Effectiveness and Safety of Polyethylene Glycol Electrolyte Solution Versus Lactulose for Treatment of Hepatic Encephalopathy: A Systematic Review and Meta-analysis.

BACKGROUND: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome associated with liver failure and/or portal systemic shunting. Polyethylene glycol (PEG) electrolyte solution is a commonly used for catharsis of gut, which has been demonstrated to relieve HE in a number of randomized controlled trials. The aim of this paper was to evaluate the comparative efficacy and safety of PEG with lactulose for current HE treatment. METHODS: PEG electrolyte solution versus lactulose of HE was deeply studied by conducting a systematic search in electronic databases and other sources until December 31, 2020. The PRISMA statement recommended the use of meta-analysis with 95% confidence interval (CI), relative risk (RR), and weighted mean deviation (WMD) as the estimated effect size. A sensitivity analysis was performed comprehensively to present the risk of bias and the source of heterogeneity. RESULTS: A total of 434 patients were involved in 7 randomized studies. It is found that there was a significant advantage of PEG therapy in the increase of clinical efficacy (RR=1.46; 95% CI: 1.26-1.68; P=0.000; I2=0.0%) and the decrease of hospital stay (WMD=-1.78; 95% CI: -2.72 to 0.85; P=0.000; I2=90.1%). There was no significant difference in the incidence of adverse events (RR=0.75; 95% CI: 0.48-1.19; P=0.222>0.05; I2=7.2%) and the level of serum ammonia (WMD=9.02; 95% CI: -14.39 to 32.43; P=0.45>0.05; I2=84.9%) after 24 hours between the 2 groups. CONCLUSIONS: The results prove that PEG has a beneficial effect on the treatment of HE. Compared with lactulose, PEG can lead to more rapid HE resolution during the first 24 hours and shorten the length of stay without increasing the rate of adverse effects.

Comparison of Al18F- and 68Ga-labeled NOTA-PEG4-LLP2A for PET imaging of very late antigen-4 in melanoma.

Malignant melanoma is an aggressive cancer with poor prognosis. Very late antigen-4 (VLA-4) is overexpressed in melanoma and many other tumors, making it an attractive target for developing molecular diagnostic and therapeutic agents. We compared Al18F- and 68Ga-labeled LLP2A peptides for PET imaging of VLA-4 expression in melanoma. The peptidomimetic ligand LLP2A was modified with chelator 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA), and the resulting NOTA-PEG4-LLP2A peptide was then radiolabeled with Al18F or 68Ga. The two labeled peptides were assayed for in vitro and in vivo VLA-4 targeting efficiency. Good Al18F and 68Ga radiolabeling yields were achieved, and the resulting PET tracers showed good serum stability. In the in vivo evaluation of the B16F10 xenograft mouse model, both tracers exhibited high accumulation with good contrast in static PET images. Compared with 68Ga-NOTA-PEG4-LLP2A, Al18F-NOTA-PEG4-LLP2A resulted in relatively higher background, including higher liver uptake (1 h: 20.1 ± 2.6 vs. 15.3 ± 1.7%ID/g, P < 0.05; 2 h: 11.0 ± 1.2 vs. 8.0 ± 0.8%ID/g, P < 0.05) and lower tumor-to-blood ratios (2.5 ± 0.4 vs. 3.3 ± 0.5 at 1 h, P < 0.05; 5.1 ± 0.9 vs. 7.3 ± 0.6 at 2 h, P < 0.01) at some time points. The results obtained from the mice blocked with unlabeled peptides and VLA-4-negative A375 xenografts groups confirmed the high specificity of the developed tracers. Despite the relatively high liver uptake, both Al18F-NOTA-PEG4-LLP2A and 68Ga-NOTA-PEG4-LLP2A exhibited high VLA-4 targeting efficacy with comparable in vivo performance, rendering them promising candidates for imaging tumors that overexpress VLA-4.

The Opposed Effects of Polyvinylpyrrolidone K30 on Dissolution and Precipitation for Indomethacin Supersaturating Drug Delivery Systems.

Amorphous solid dispersions (ASD) are one of the most important supersaturating drug delivery systems (SDDS) for poorly water-soluble drugs to improve their bioavailability. As a result of thermodynamic instability, drug molecules tend to precipitate during storage and dissolution in gastrointestinal tract. Various precipitation inhibitors (PI) have been widely used to improve the stability in the past decade. However, most studies have investigated the inhibiting capability of PI on drug precipitation, rarely considering their potential hindering effect on the drug dissolution. The present study designed an ASD of Indomethacin (IND) and Eudragit® EPO by hot melt extrusion to investigate the influence of the added PI (PVP-K30) into ASD both on dissolution and precipitation. The precipitation study by solvent shift method indicated PVP-K30 could inhibit the precipitation of IND significantly. The dissolution study in different concentrations of PVP-K30 showed when the concentration increased above 50 µg/mL, PVP-K30 displayed an acceptable precipitation inhibition without drug concentration decline but an unexpected dissolution impediment with the reduction of maximum concentration platform. The dissolution tests of physical mixtures (PMs) of ASD and PVP-K30 also showed the precipitation inhibition and dissolution impediment when more than 2% PVP-K30 in PMs. This opposed effect of PVP-K30 was strengthen in ternary systems prepared by hot melt extruding the mixtures of IND, Eudragit® EPO and PVP-K30. All of these results proved the PI may be a double-edged sword for the opposed effects of precipitation inhibition and dissolution impediment, which should be carefully considered in the design and development of SDDS.

Self-Amplified Photodynamic Therapy through the 1 O2 -Mediated Internalization of Photosensitizers from a Ppa-Bearing Block Copolymer.

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non-selective release of photosensitizers still exist. Herein, we report a 1 O2 -responsive block copolymer (POEGMA-b-P(MAA-co-VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1 O2 ) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1 O2 -responsiveness of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer enabled the realization of self-amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.

Improvement of dissolution and tabletability of carbamazepine solid dispersions with high drug loading prepared by hot-melt extrusion.

Solid dispersions (SDs) have made great progress in the improvement of dissolution for poorly soluble drugs, however the low drug loading still limits their wide application. In the present paper, high carbamazepine (CBZ) loaded SDs with excellent dissolution and tabletability were prepared and characterized. The CBZ SDs were prepared with Eudragit EPO as carrier by hot-melt extrusion (HME) in the drug: carrier ratio of 4:1. Powder X-ray diffraction, differential scanning calorimetry, fourier transform infrared spectroscopy and powder dissolution was carried out to characterize the SDs. The results showed that the crystalline form the polymorph of CBZ in SDs was transformed into form I from form III after extruded at 140 °C. Wettability and microstructure of CBZ SDs were improved by the HME process, which promoted the dissolution significantly. More than 85 % drug dissolved within 5 min from CBZ SDs with even only 20 % Eudragit EPO as carrier. CBZ SDs tablets were prepared by direct tableting with a universal material testing machine at various compaction pressures. Compactibility and tabletability were enhanced significantly by the HME process. All of these results showed the CBZ SDs prepared by HME with 80 % CBZ and 20 % Eudragit EPO could improve the dissolution and tabletability significantly.

Physiological responses and molecular mechanism of Chlorella sorokiniana to surgical mask exudates in wastewater.

Microalgae-based bioremediation is likely to be challenged by the microplastics (MPs) in wastewater induced by the widely use of surgical masks (SMs) during COVID-19. However, such toxic impact was generally evaluated under high exposure concentrations of MPs, which was not in agreement with the actual wastewater environments. Therefore, this study investigated the microalgal cellular responses to the surgical mask exudates (SMEs) in wastewater and explored the underlying inhibitory mechanism from the molecular perspective. Specifically, 390 items/L SMEs (including 200 items/L MPs which was the actual MP level in wastewater) significantly inhibited nutrient uptake and photosynthetic activities interrupted peroxisome biogenesis and induced oxidative stress which destroyed the structure of cell membrane. Moreover, the SMEs exposure also affected carbon fixation pathways, suppressed ABC transporters while promoted oxidative phosphorylation processes for the ATP accumulation These comprehensive processes led to an 8.5% reduced microalgae growth and variations of cellular biocomponents including lipid, carbohydrate, and protein. The increased carotenoids and consumed unsaturated fatty acid were considered to alleviate the SMEs-induced stress, and the enhanced EPS secretion facilitated the homogeneous aggregation. These findings will enhance current understandings of the SMEs effects in wastewater on microalgae and further improve the practical relevance of microalgae wastewater bioremediation technology.

Metal-Driven Autoantifriction Function of Artificial Hip Joint.

The service life of an artificial hip joint is limited to 10-15 years, which is not ideal for young patients. To extend the lifespan of these prostheses, the coefficient of friction and wear resistance of metallic femoral heads must be improved. In this study, a Cu-doped titanium nitride (TiNX -Cu) film with "autoantifriction" properties is deposited on a CoCrMo alloy via magnetron sputtering. When delivered in a protein-containing lubricating medium, the Cu in TiNX -Cu quickly and consistently binds to the protein molecules in the microenvironment, resulting in the formation of a stable protein layer. The proteins adsorbed on the TiNX -Cu surface decompose into hydrocarbon fragments owing to the shear stress between the Al2 O3 /TiNX -Cu tribopair. The synergistic effect of the catalysis of Cu and shear stress between the Al2 O3 /TiNX -Cu tribopair transforms these fragments into graphite-like carbon tribofilms with an antifriction property. These tribofilms can simultaneously reduce the friction coefficient of the Al2 O3 /TiNX -Cu tribopair and enhance the wear resistance of the TiNX -Cu film. Based on these findings, it is believed that the autoantifriction film can drive the generation of antifriction tribofilms for lubricating and increasing the wear resistance of prosthetic devices, thereby prolonging their lifespan.

Bio- and photo-lability of dissolved organic matter in the Pearl River (Zhujiang) estuary.

We investigated the bio- and photo-lability of dissolved organic matter (DOM) from the head, mixing zone, and mouth of the Pearl River estuary. At all three sites, bio- and photo-refractory dissolved organic carbon (DOC) and biorefractory chromophoric DOM (CDOM) dominated over the corresponding bio- and photo-labile constituents, while photolabile CDOM dominated over photo-refractory CDOM. Relative to the mixing-zone and mouth waters, the headwater was enriched with bio- and photo-labile DOC and photolabile CDOM and depleted with biolabile CDOM. Biolabile DOC was richer than photolabile DOC in the headwater, while photolabile CDOM was richer than biolabile CDOM at all three sites. Pre-biotransformation inhibited, stimulated, or had little impact on DOM photodegradation, depending on site. Ultra-violet absorption coefficients are indicators of bio- and photo-refractory DOC. The relative proportions of transparent and chromophoric DOM control the turnover of biolabile DOC and the effect of pre-biotransformation on DOM photodegradation.

Graphene oxide coated Titanium Surfaces with Osteoimmunomodulatory Role to Enhance Osteogenesis.

Graphene oxide (GO) and its derivatives are currently being explored for the modification of bone biomaterials. However, the effect of GO coatings on immunoregulation and subsequent impacts on osteogenesis are not known. In this study, GO was coated on pure titanium using dopamine. GO-coated titanium (Ti-GO) surfaces exhibited good biocompatibility, with the ability to stimulate the expression of osteogenic genes, and extracellular matrix mineralization in human mesenchymal stromal cells (hMSCs). Interestingly, it was found that GO-coated surfaces could manipulate the polarization of macrophages and expression of inflammatory cytokines via the Toll-like receptor pathway. Under physiological conditions, Ti-GO activated macrophages and induced mild inflammation and a pro-osteogenic environment, characterized by a slight increase in the levels of proinflammatory cytokines, as well as increased expression of the TGF-ß1 and oncostatin M genes. In an environment mimicking acute inflammatory conditions, Ti-GO attenuated inflammatory responses, as shown by the downregulation of proinflammatory cytokines. Conditioned medium collected from macrophages stimulated by Ti-GO played a significant stimulatory role in the osteogenic differentiation of hMSCs. In summary, GO-coated surfaces displayed beneficial immunomodulatory effects in osteogenesis, indicating that GO could be a potential substance for the modification of bone scaffolds and implants.

Red blood cell membrane-coated upconversion nanoparticles for pretargeted multimodality imaging of triple-negative breast cancer.

Upconversion nanoparticles (UCNPs) have been widely employed for tumor imaging using magnetic resonance imaging (MRI) and upconversion luminescence (UCL) imaging. The short blood clearance time and immunogenicity of UCNPs have limited their further application in vivo. We have designed UCNPs camouflaged with an exterior red blood cell (RBC) membrane coating (RBC-UCNPs) to solve these problems. Moreover, because of some intrinsic disadvantages of MRI and UCL imaging, we investigated the use of pretargeted RBC-UCNPs for positron-emission tomography (PET) imaging to obtain more comprehensive information. Our data showed that RBC-UCNPs retained the immunity feature from the source cells and the superior optical and chemical features from the pristine UCNP cores. The tumor-targeting ability of RBC-UCNPs was enhanced by binding 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000] (DSPE-PEG-FA) molecules onto the cell membranes. PET imaging with short half-life radionuclides to visualize the RBC-UCNPs was successfully realized by a combination of pre-targeting and in vivo click chemistry. Blood chemistry, hematology, and histologic analysis suggested good in vivo biocompatibility of the RBC-UCNPs. Our method provides a new potential biomedical application of biomimetic nanoparticles.

Slp-coated liposomes for drug delivery and biomedical applications: potential and challenges.

Slp forms a crystalline array of proteins on the outermost envelope of bacteria and archaea with a molecular weight of 40-200 kDa. Slp can self-assemble on the surface of liposomes in a proper environment via electrostatic interactions, which could be employed to functionalize liposomes by forming Slp-coated liposomes for various applications. Among the molecular characteristics, the stability, adhesion, and immobilization of biomacromolecules are regarded as the most meaningful. Compared to plain liposomes, Slp-coated liposomes show excellent physicochemical and biological stabilities. Recently, Slp-coated liposomes were shown to specifically adhere to the gastrointestinal tract, which was attributed to the "ligand-receptor interaction" effect. Furthermore, Slp as a "bridge" can immobilize functional biomacromol-ecules on the surface of liposomes via protein fusion technology or intermolecular forces, endowing liposomes with beneficial functions. In view of these favorable features, Slp-coated liposomes are highly likely to be an ideal platform for drug delivery and biomedical uses. This review aims to provide a general framework for the structure and characteristics of Slp and the interactions between Slp and liposomes, to highlight the unique properties and drug delivery as well as the biomedical applications of the Slp-coated liposomes, and to discuss the ongoing challenges and perspectives.

Dual-inflammatory cytokines on TiO2 nanotube-coated surfaces used for regulating macrophage polarization in bone implants.

Excessive immune responses following the use of implantable, biomaterial-based medical devices represent a substantial challenge for treatment efficacy and patient well-being. Specifically, after implantation, pro-inflammatory M1 macrophages are activated by cytokines such as interferon-γ (IFN-γ) followed by anti-inflammatory M2 macrophages polarized by cytokines including interleukin-4 (IL-4), leading to healing and long-term stability of implants. Here, we report the loading of an immunomodulatory cytokine,IL-4, into TiO2 nanotubes (TNTs) followed by hydrogel coating on the TNTs for subsequent release of IL-4. Finally, IFN-γ was added onto the gel layer to effect rapid release. The release rates of both cytokines from the samples were monitored using an immersion test in phosphate-buffered solution. The cytocompatibility of the sample was evaluated using cultures of osteoblasts and macrophages. Macrophage phenotype switching in vitro was examined via cytokine secretion and gene expression analyses. In vitro testing showed that the sample could stimulate macrophage polarization from the M1 to M2 phenotype at the desired period owing to temporal release of IFN-γ and IL-4. Another biomaterial containing only IL-4 in TNTs was also able to modulate the transformation of M1 to M2 although with weaker effect than that containing IFN-γ and IL-4. The biomaterial may be useful as an osteoimplant in vivo owing to the inflammation caused by a wound or implantation. This study provided biomaterials capable of facilitating smooth M1 to M2 macrophages switching, which might be helpful to research immune responses of tissues to implants and will likely contribute to the development of bone substitute materials. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1878-1886, 2018.

Macrophage phenotype switch by sequential action of immunomodulatory cytokines from hydrogel layers on titania nanotubes.

Inflammatory response occurring between tissues and implants after implantation has attracted increasing attention because it can cause local tissue necrosis and even implant failure. Macrophages play a key role in all stages of inflammation. Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages comprise two main phenotypes and the switch from M1 to M2 at specific time points is important for wound healing and tissue regeneration. Therefore, we hypothesized that biomaterial systems capable of facilitating macrophage phenotype switching should attenuate inflammation and enhance healing. To this end, a system of double hydrogel layers on titania nanotubes (TNT) was prepared as reservoir to modulate the release of interleukin-4 (IL-4) and interferon-γ (IFN-γ). In this system, IL-4, an anti-inflammatory cytokine, was loaded in TNT and IFN-γ, a pro-inflammatory cytokine, was located between two hydrogel layers of chitosan/ß-glycerophosphate disodium and carboxymethyl chitosan/genipin. IFN-γ released rapidly in 3 days, whereas IL-4 exhibited a sustained release profile. In culture with mesenchymal stem cells and macrophages, this system displayed good cytocompatibility and significantly promoted cell proliferation. Macrophage phenotype switch was determined by ELISA, FACS and PCR. The results manifested that IFN-γ released from the system stimulated switching of macrophages to M1 in 3 days, whereas sustained release of IL-4 polarized macrophages to M2 after 4 days. This system can modulate macrophage phenotype switching from M1 to M2 by sequential action of the two cytokines, and might be used to research immune response between tissues and implants. The present study also provided a novel strategy for designing functional biomaterials.

Controllable release of interleukin-4 in double-layer sol-gel coatings on TiO2 nanotubes for modulating macrophage polarization.

Classically activated M1 macrophages and alternatively activated M2 macrophages play key roles in regulating immune responses. M1 macrophages initiate angiogenesis in the early stages of wound healing or after implantation. However, their prolonged activation can lead to chronic inflammation. We speculated that biomedical implants with specific properties can induce a shift from M1 to M2 macrophages at a specific time point to promote tissue repair and wound healing. To investigate this possibility, drug-loaded double-layer sol-gel coatings were fabricated on TiO2 nanotubes (TNTs), which were used to modulate the switch from the M1 to the M2 phenotype by controlled release of interleukin (IL)-4. The lower sol-gel layer with IL-4 consisted of a carboxymethyl chitosan (CMCS) hydrogel, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, and N-hydroxysuccinimide as a crosslinker (IL4/TNT). The upper layer fabricated on the IL4/TNT sample was another type of CMCS hydrogel that used genipin (GP) as a crosslinker (GP/IL4/TNT). We found that IL-4 was released from GP/IL4/TNTs in a controlled manner, with the greatest release occurring after 72 h. GP/IL4/TNT stimulated the polarization of macrophages from the M1 to M2 phenotype after the macrophage polarization from the M0 to M1 phenotype. This provides a template for the fabrication of biomaterials that can direct macrophage polarization and stimulate tissue regeneration following the initial inflammatory response to implants.

Novel pathogenic RECQL4 variants in Chinese patients with Rothmund-Thomson syndrome.

BACKGROUND: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder mainly characterized by cutaneous poikiloderma, sparse hair, short stature and skeletal defects. Deleterious mutations in the RecQ-like DNA helicase type 4 (RECQL4) gene have been detected in approximately two-thirds of RTS cases. METHODS: Three Chinese patients from two unrelated families were enrolled for clinical evaluation. Targeted next-generation sequencing (NGS) using a custom panel consisting of 705 short-stature-related genes was performed for the probands. Variants detected by NGS were confirmed by Sanger sequencing and examined in family members. RESULTS: The probands presented with characteristic features of severe growth delay, poikiloderma mostly on the face, buttocks and extremities, sparse or absent hair, eyelashes, and eyebrows, forearm reduction defects, small hands with hypoplasia of the middle phalanx (little finger) in one of the probands, epicanthus, hypertelorism, and dental abnormalities. In addition, novel auricle features and other rare facial features, including narrow palpebral fissure, depressed nasal bridge, and small chin were exhibited. Four novel RECQL4 variants were identified, including three pathogenic frameshift variants, c.1724_1725delAC, p.His575fs*7; c.2421dupT, p.Asp808*; c.1770_1807del, p.Pro591fs*2, and one likely pathogenic missense variant, c.691G>A, p.Gly231Ser. CONCLUSION: Our study expands the mutational spectrum of RECQL4 gene and reveals novel phenotypes observed in Chinese RTS patients.

Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

PURPOSE: The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. METHODS: The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. RESULTS: The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution. CONCLUSION: Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

Extracellular polymeric substances for Zn (II) binding during its sorption process onto aerobic granular sludge.

The aim of this study was to evaluate the interaction between extracellular polymeric substances (EPS) and Zn (II) during the sorption process of Zn (II) onto aerobic granular sludge. Batch results showed that the adsorption rate of Zn (II) onto aerobic granular sludge was better fitted with pseudo-second order kinetics model, and the adsorption isotherm data agreed well with Freundlich equation. Extracellular polymeric substances (EPS) for Zn (II) binding during sorption process was investigated by using a combination of three-dimensional excitation-emission matrix (3D-EEM), synchronous fluorescence spectra, two-dimensional correlation spectroscopy (2D-COS) and Fourier transform infrared spectroscopy (FTIR). Results implied that the main composes of EPS, including polysaccharide (PS) and protein (PN), decreased from 5.92±0.13 and 23.55±0.76 mg/g SS to 4.11±0.09 and 9.55±0.68 mg/g SS after the addition of different doses of Zn (II). 3D-EEM showed that the intensities of PN-like substances and humic-like substances were obviously decreased during the sorption process. According to synchronous fluorescence spectra, the quenching mechanism between PN-like substances and Zn (II) was mainly caused by a static quenching process. Additionally, 2D-COS indicated that PN-like substances were more susceptible to Zn (II) binding than humic-like substances. It was also found that the main functional groups for complexation of Zn (II) and EPS were OH groups, N-H groups and C=O stretching vibration. The findings of this study are significant to reveal the fate of heavy metal during its sorption process onto aerobic granular sludge through EPS binding, and provide useful information on the interaction between EPS and heavy metal.

Toxicity assessment of 4-chlorophenol to aerobic granular sludge and its interaction with extracellular polymeric substances.

The main objective of this study was to evaluate the toxicity of 4-chlorophenol (4-CP) to aerobic granular sludge in the process of treating ammonia rich wastewater. In the short-term exposure of 4-CP of 5 and 10 mg/L, ammonia nitrogen removal efficiencies in the batch reactors decreased to 87.18±2.81 and 41.16±3.55%, which were remarkably lower than that of control experiment (99.83±0.54%). Correspondingly, the respirometric activities of heterotrophic and autotrophic bacteria of aerobic granular sludge were significantly inhibited in the presence of 4-CP. Moreover, the main components of extracellular polymeric substances (EPS) including polysaccharides and proteins increased from 18.74±0.29 and 22.57±0.34 mg/g SS to 27.79±0.51 and 24.69±0.38 mg/g SS, respectively, indicating that the presence of 4-CP played an important role on the EPS production. Three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy further showed that the intensities of EPS samples were obviously quenched with the increased of 4-CP concentrations. To be more detailed, synchronous fluorescence spectra indicated that the interaction between EPS and 4-CP was mainly caused by tryptophan residues. The mechanism of fluorescence quenching belongs to static quenching with a formation constant (KA) of 0.07×10(4) L/mol, implying the strong formation of EPS and 4-CP complex. The results could provide reliable and accurate information to determine the potential toxicity of 4-CP on the performance of aerobic granular sludge system.