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1.
Environ Int ; 137: 105540, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032776

RESUMO

The prevalence and accumulation of antibiotic resistance genes (ARGs) were frequently detected in biological wastewater treatment processes, which might cause potential health crisis to human. In present study, the fates of ARGs during two different aerobic granular sludge (AGS) cultivation processes were investigated. The results showed that traditional AGS (T-AGS) cultivation process and enhanced AGS (E-AGS) cultivation process had significant differences (P < 0.005) in ARGs shift patterns. E-AGS process had higher average relative abundance (0.280 ± 0.079) of ARGs than T-AGS process (0.130 ± 0.041), while the intensity of ARGs enrichment during E-AGS (1.52-5.29 fold) was lower than T-AGS (3.79-75.31 fold) process. TnpA and intI1 as two different types of mobile genetic elements (MGEs) carrying ARGs, were observed to contribute significantly to the horizontal gene transfer (HGT) during T-AGS (r = 0.902, P < 0.050) and E-AGS (r = 0.823, P < 0.001) processes, respectively. Higher HGT level took place and more possible potential hosts (25 hosts) harboring ARGs were detected during E-AGS process comparing with T-AGS process (17 hosts). Meanwhile, over large AGS might increase the propagation of several antibiotic deactivation ARGs, so it was not advised. Overall, whether during T-AGS or during E-AGS process which was applied in a pilot-scale sequencing batch reactor treating municipal wastewater, the accumulation and spread of ARGs were inevitable. It should be valued that some suitable pre-treatments of seed sludge should be executed, meanwhile, advanced treatment for removing of ARGs in AGS should be conducted to maintain the relative abundances of ARGs at relatively low level.

2.
Sci Rep ; 10(1): 2566, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054970

RESUMO

Wind erosion is a huge challenge for ecologists to stabilize sand dunes and to change them into stable productive ecosystems. In order to better understand its role in the process of ecological restoration, the sediment grain-size characteristics of compound sand barrier were evaluated through field experimental observation. The results indicated that the compound sand barrier was mainly composed of extremely fine sand and fine sand, and the fine sand and extremely fine sand in the inner side were higher than the east and west sides of the compound sand barrier. Due to the blocking effect of compound sand barrier, the Sorting Coefficient became better, the Skewness belonged to the positive deviation and the Kurtosis presented leptokurtosis distribution. Moreover, while the cumulative frequency distribution curve in the inner side became steeper, the slope increased and reached the top of the curve ahead of time. The effect of wind environment and vegetation coverage on the surface sediments showed that the average annual wind velocity and vegetation coverage was negatively correlated with the average grain-size, but positively correlated with the Sorting Coefficient. There was a significant correlation among the annual wind speed, vegetation coverage, average grain-size and Sorting Coefficient, which indicated that vegetation coverage and wind environment was the key factor leading to the difference of surface sediments in this area. Collectively, the establishment of compound sand barrier is one of the most effective methods of sand-fixing with engineering measure in the arid desert regions. Therefore, given the complexities of agricultural systems, stubble retention and black film covered during harvesting and incorporation of the stubble into soil in the next spring appears to be the best choice in the dry northern China where farmlands suffer serious wind erosion.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32037847

RESUMO

AIMS: Acetaminophen (APAP) overdose leads to acute liver injury by inducing hepatic mito-chondrial oxidative stress and inflammation. However, the molecular mechanisms involved are still unclear. Farnesoid X receptor (FXR) serves as a therapeutic target for the treatment of liver disorders, whose activation has been proved to protect APAP-induced hepatotoxicity. In this study, we examined whether FXR activation by schaftoside, a naturally-occurring flavonoid from Desmodium styracifolium, could protect mice against APAP-induced hepatotoxicity via regulation of oxidative stress and inflammation. RESULTS: We firstly found that schaftoside exhibited potent protective effects against APAP-induced hepatotoxicity in mice. The study reveals that schaftoside is a potential agonist of FXR, which protects mice from hepatotoxicity mostly via regulation of oxidative stress and in-flammation. Mechanistically, the hepatoprotective of SS is associated with the induction of the genes of phase II detoxifying enzymes (e.g. UGT1A1, GSTα1), phase III drug efflux transporters (e.g. BSEP, OSTß) and GSH metabolism-related enzymes (e.g. Gclm, Gclc). More importantly, SS-mediated FXR activation could fine-tune the pro- and anti-inflammatory eicosanoids genera-tion via altering eicosanoids metabolic pathway, thereby resulting in decrease of hepatic inflam-mation. In contrast, FXR deficiency can abrogate these-above effects. Innovation and Conclusion: Our results provided the direct evidence that FXR activation by schaftoside could attenuate APAP-induced hepatotoxicity via inhibition of NF-κB signaling and fine-tuning the generation of pro-inflammatory mediators' eicosanoids. Our findings indicate that strategies to activate FXR signaling in hepatocytes may provide a promising therapeutic approach to alleviate liver injury induced by APAP overdose.

4.
Pharmacogenomics J ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32042095

RESUMO

Diffuse Large B-cell Lymphoma (DLBCL), a heterogeneous disease, is influenced by complex network of gene interactions. Most previous studies focused on individual genes, but ignored the importance of intergenic correlations. In current study, we aimed to explore the association between gene networks and overall survival (OS) of DLBCL patients treated with CHOP-based chemotherapy (cyclophosphamide combination with doxorubicin, vincristine and prednisone). Weighted gene co-expression network analysis was conducted to obtain insights into the molecular characteristics of DLBCL. Ten co-expression gene networks (modules) were identified in training dataset (n = 470), and their associations with patients' OS after chemotherapy were tested. The results were validated in four independent datasets (n = 802). Gene ontology (GO) biological function enrichment analysis was conducted with Metascape. Three modules (purple, brown and red), which were enriched in T-cell immune, cell-cell adhesion and extracellular matrix (ECM), respectively, were found to be related to longer OS. Higher expression of several hub genes within these three co-expression modules, for example, LCP2 (HR = 0.77, p = 5.40 × 10-2), CD2 (HR = 0.87, p = 6.31 × 10-2), CD3D (HR = 0.83, p = 6.94 × 10-3), FYB (HR = 0.82, p = 1.40 × 10-2), GZMK (HR = 0.92, p = 1.19 × 10-1), FN1 (HR = 0.88, p = 7.06 × 10-2), SPARC (HR = 0.82, p = 2.06 × 10-2), were found to be associated with favourable survival. Moreover, the associations of the modules and hub genes with OS in different molecular subtypes and different chemotherapy groups were also revealed. In general, our research revealed the key gene modules and several hub genes were upregulated correlated with good survival of DLBCL patients, which might provide potential therapeutic targets for future clinical research.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32073710

RESUMO

Heteroatom-doped carbon materials have rapidly emerged as promising candidates for supercapacitor applications, owing to their tunable surface functionalities and exceptional performances. Although tremendous efforts have been devoted to understanding the origin of boosted charge storage on heteroatom-doped carbons, none of the present studies has shown a whole landscape. Herein, by both experimental evidence and theoretical simulation, we demonstrate that the heteroatom doping does not only result in a broadened operating voltage, but also successfully promotes the specific capacitance in aqueous supercapacitors. To be more specific, the electrolyte cations adsorbed on heteroatom-doped carbon can effectively inhibit hydrogen evolution reaction, a key step of water decomposition during the charging process, which broadens the voltage window of aqueous electrolytes even beyond the thermodynamic limit of water (1.23 V). In addition, the reduced adsorption energy of heteroatom-doped carbon consequently leads to more stored cations on the heteroatom-doped carbon surface, thus yielding a boosted charge storage performance.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 231: 118105, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32006914

RESUMO

Four rhodamine-based fluorescent probes M1-M4 were synthesized in one step using Mannich reaction. The Mannich reaction based approach has the advantages of simplicity, good yield and excellent atomic economy. The structures were determined by 1H NMR, 13C NMR, IR and HRMS. The probe M3 as a representative compound was characterized by single-crystal X-ray analyses. The fluorescence and absorbance spectra research of the probes demonstrated that they could be used as Fe3+-selective fluorescent probes with good sensitivity, excellent linearity, and outstanding anti-interference in acetonitrile/Tris-HCl buffer solution (3:7, V/V; pH = 7.4). Moreover, confocal laser scanning microscopy experiments have proven that the probe M3 was successfully used for fluorescence imaging in MCF-7 cells.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31975323

RESUMO

F8 intron 22 inversion (Inv22) accounts for about 40% of severe hemophilia A (HA) cases and is mainly genotyped by long-distance PCR (LD-PCR) or inverse-PCR (I-PCR). These methods require long separation times or enzymatic digestion. We aimed to shorten the separation time of LD-PCR. Long-read sequencing was applied for LD-PCR products from 20 Inv22 patients and 4 controls to validate the differences between products generated using P-Q and P-B primer pairs in LD-PCR. We then confirmed two unique regions (chrX: 154879481-154880814, chrX: 155376388-155376505, GRCh38) in the PCR products from P-Q and P-B primer pairs, respectively. The nested PCR P1, Q1, and B1 primers were located near the homologous sequence and two unique regions, respectively. The P1-Q1 and P1-B1 primer pairs generated 1621 bp and 540 bp fragments, respectively, and the Inv22 carriers produced both fragments. In total, 228 previously diagnosed subjects including 39 Inv22 carriers, 52 Inv22 patients, 82 Inv22 negative males, and 55 Inv22 negative females were genotyped using nested PCR, and the results revealed excellent sensitivity and specificity (100 and 100%, respectively). The separation time was shortened from 5 to 0.5 h. Therefore, we present a rapid genotyping method for F8 Inv22 by nested PCR based on LD-PCR.

8.
J Exp Clin Cancer Res ; 39(1): 13, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941533

RESUMO

BACKGROUND: Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal adenocarcinoma (PDAC) have not been revealed yet. METHODS: The expression of MOB1 and lysine demethylase 2B (KDM2B) in PDAC and adjacent normal pancreas tissues were measured. Also, the underlying mechanisms of altered MOB1 expression and its impact on PDAC biology were investigated. RESULTS: We revealed for the first time that MOB1 was decreased expression in PDAC and was a statistically significant independent predictor of poor survival, and restored expression of MOB1 suppressed the proliferation, migration and invasion of PDAC cells. Further studies demonstrated that KDM2B directly bound to the promoter region of MOB1, and suppressed the promoter activity of MOB1 and transcriptionally inhibited the MOB1 expression. Furthermore, KDM2B regulated Hippo pathway and promoted PDAC proliferation, migration and invasion via MOB1. CONCLUSION: This study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression.

9.
Chin J Nat Med ; 18(1): 47-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31955823

RESUMO

KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg·kg-1), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg-1, respectively) plus indomethacin, and sucralfate (1.71 mL·kg-1) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL·kg-1) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin).

10.
World Neurosurg ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31981784

RESUMO

This article explores the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the prognosis of gliomas, and judges the relevant factors affecting the prognosis of gliomas. for reference. patient. This article used Cox proportional hazards model to retrospectively analyze clinical data of 81 complete neuroglioma patients from the same neurosurgery medical team from January 2012 to November 2018, including magnetic resonance dynamic imaging data. In order to determine the prognostic factors, P <0.05 was used as the statistical standard, and the survival curve of statistically significant factors was drawn by Kaplan-Meier method. The results showed that Cox proportional hazard model analysis showed that preoperative KPS score, age, tumor pathological grade, postoperative radiotherapy, temozolomide use, and Ki-67 expression had an impact on the prognosis of patients with neuroglioma. Multivariate analysis and MRI imaging data showed that age, tumor grade, preoperative KPS score, postoperative radiotherapy, and Ki-67 expression were prognostic factors for patients with glioma. The older the age, the higher the pathological grade, the higher the Ki-67 expression level, the lower the KPS score before surgery, and the worse the prognosis. Postoperative radiotherapy and appropriate temozolomide chemotherapy will help improve the prognosis of patients with neuroglioma.

11.
Transfusion ; 60(2): 334-342, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31909495

RESUMO

BACKGROUND: Chinese blood donors with unconfirmed serological and/or molecular screening results are deferred permanently. This study investigated the implementation and performance of a follow-up program aiming to improve the notification and management of deferred donors in Dalian, China. STUDY DESIGN AND METHODS: From January 2013 to February 2018, 411,216 donations were tested for HBsAg, anti-HCV, anti-HIV/HIV antigen, and antibodies to Treponema pallidum. HBV, HCV, and HIV nucleic acid testing (NAT) was performed in mini-pools of six or in individual donations (IDs). Reactive donations were evaluated further with alternative serological assays and ID-NAT re-testing. A follow-up procedure was developed to evaluate a subset of deferred donors that were either potential NAT yield cases, serology non-reactive and NAT non-repeated reactive (NRR), or serology NRR irrespective of NAT result. RESULTS: Serological and molecular routine, plus supplemental testing, identified HBV, HCV, HIV, and TP in 503 (0.12%), 392 (0.09%), 156 (0.04%), and 2041 (0.49%) donations, respectively. Overall, 683 of 4156 (16.4%) eligible donors and 205 donors deferred prior 2013 participated in the program. They included 664 serology NRR and 224 NAT yield cases, and 58.8% repeat donors. All markers combined, follow-up documented false reactivity, primary acute infections, and OBI in 61.9% (550/888), 3.3% (29/888), and 12.8% (114/888) of these donors, respectively. Isolated anti-HBc or anti-HBs reactivity was observed in 22% of cases. CONCLUSION: Follow-up testing refined infection status in 78.0% (693/888) of deferred donors with unconfirmed screening results. This high false-positive rate encouraged to reevaluate the current screening strategies and to consider donor reentry.

12.
Anal Chem ; 92(4): 3417-3425, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31970977

RESUMO

In vitro assessment of lipid intermembrane transfer activity by cellular proteins typically involves measurement of either radiolabeled or fluorescently labeled lipid trafficking between vesicle model membranes. Use of bilayer vesicles in lipid transfer assays usually comes with inherent challenges because of complexities associated with the preparation of vesicles and their rather short "shelf life". Such issues necessitate the laborious task of fresh vesicle preparation to achieve lipid transfer assays of high quality, precision, and reproducibility. To overcome these limitations, we have assessed model membrane generation by bicelle dilution for monitoring the transfer rates and specificity of various BODIPY-labeled sphingolipids by different glycolipid transfer protein (GLTP) superfamily members using a sensitive fluorescence resonance energy transfer approach. Robust, protein-selective sphingolipid transfer is observed using donor and acceptor model membranes generated by dilution of 0.5 q-value mixtures. The sphingolipid transfer rates are comparable to those observed between small bilayer vesicles produced by sonication or ethanol injection. Among the notable advantages of using bicelle-generated model membranes are (i) easy and straightforward preparation by means that avoid lipid fluorophore degradation and (ii) long "shelf life" after production (≥6 days) and resilience to freeze-thaw storage. The bicelle-dilution-based assay is sufficiently robust, sensitive, and stable for application, not only to purified LTPs but also for LTP activity detection in crude cytosolic fractions of cell homogenates.

13.
ACS Appl Mater Interfaces ; 12(7): 7984-7994, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31971362

RESUMO

Nanomedicine uses nanotechnology-based strategies for precision tumor therapy, including passive and ligand-mediated active tumor targeting by nanocarriers. However, the possible biotoxicity of chemosynthetic nanovectors limits their clinical applications. A novel natural egg yolk lipid nanovector (EYLN) was developed for effective loading and delivery of therapeutic agents. Lipids were extracted from egg yolks and reassembled into nanosized particles. EYLNs' stability, cellular uptake, toxicity, and delivery capacity for therapeutic agents were evaluated in vitro. The systemic toxicity and biodistribution of EYLNs were analyzed in normal mice, and the therapeutic effects of doxorubicin (Dox)-loaded EYLNs were evaluated in mouse breast cancer and hepatoma models. EYLNs had a particle size of ∼40 nm and a surface ζ-potential of -45 mV and were effectively internalized by tumor cells, without showing toxicity and side effects in vitro and in vivo. Importantly, their excellent permeability and retention effect significantly enhanced the distribution of EYLNs at tumor sites, and EYLN-Dox effectively inhibited the tumor growth in both mouse models. Targeted modification with folic acid further promoted vector-mediated drug distribution in tumors. This study demonstrates that lipids with specific proportions in the egg yolk can be used to construct natural drug vectors, providing a new strategy for nano-oncology research.

14.
Oncogene ; 39(5): 1140-1151, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31641207

RESUMO

Mitochondrial pyruvate carrier 1 (MPC-1) appears to be a tumor suppressor. In this study, we determined the regulation of MPC-1 expression by Lysine demethylase 5A (KDM5A) and critical impact of this novel KDM5A/MPC-1 signaling on PDA progression. TCGA database, paired PDA and adjacent normal pancreatic tissues, PDA tissue array and cell lines were used to determine the levels of MPC-1 and KDM5A expression, and their relationship with the clinicopathologic characteristics and overall survival (OS) of PDA patients. Both in vitro and in vivo models were used to determine biologic impacts of MPC-1 and KDM5A on PDA and mitochondrial pyruvate metabolism, and the mechanism underling reduced MPC-1 expression in PDA. The expression of MPC-1 was decreased in PDA cell lines and tissues, and negatively associated with tumor poorer differentiation, lymph nodes metastasis, higher TNM stages, and patients' overall survival (OS). Functional analysis revealed that restored expression of MPC-1 suppressed the growth, invasion, migration, stemness and tumorigenicity. Re-expression of MPC-1 stimulated the mitochondrial pyruvate metabolism and inhibited glycolysis, while MPC-1-specific inhibitor UK5099 attenuated these effects. Furthermore, KDM5A bound directly to MPC-1 promoter region and transcriptionally suppressed the expression of MPC-1 via demethylation H3K4. Consistently, KDM5A expression was elevated in PDA and promoted PDA cell proliferation in vitro and tumor growth in vivo via suppressing the expression of MPC-1. The expression of KDM5A was inversely correlated with that of MPC-1 in PDA. KDM5A/MPC-1 signaling promoted PDA growth, invasion, migration, and stemness via inhibiting mitochondrial pyruvate metabolism. Targeting KDM5A/MPC-1 signaling may be an effective therapeutic strategy for PDA.

15.
Physiol Plant ; 168(1): 98-117, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31017672

RESUMO

WRKY transcription factors play a key role in the tolerance of biotic and abiotic stresses across various crop species, but the function of some WRKY genes, particularly in tomato, remains unexplored. Here, we characterize the roles of a previously unstudied WRKY gene, SlWRKY8, in the resistance to pathogen infection and the tolerance to drought and salt stresses. Expression of SlWRKY8 was up-regulated upon Pseudomonas syringae pv. tomato DC3000 (Pst. DC3000), abiotic stresses such as drought, salt and cold, as well as ABA and SA treatments. The SlWRKY8 protein was localized to the nucleus with no transcription activation in yeast, but it could activate W-box-dependent transcription in plants. The overexpression of SlWRKY8 in tomato conferred a greater resistance to the pathogen Pst. DC3000 and resulted in the increased transcription levels of two pathogen-related genes SlPR1a1 and SlPR7. Moreover, transgenic plants displayed the alleviated wilting or chlorosis phenotype under drought and salt stresses, with higher levels of stress-induced osmotic substances like proline and higher transcript levels of the stress-responsive genes SlAREB, SlDREB2A and SlRD29. Stomatal aperature was smaller under drought stress in transgenic plants, maintaining higher water content in leaves compared with wild-type plants. The oxidative pressure, indicated by the concentration of hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA), was also reduced in transgenic plants, where we also observed higher levels of antioxidant enzyme activities under stress. Overall, our results suggest that SlWRKY8 functions as a positive regulator in plant immunity against pathogen infection as well as in plant responses to drought and salt stresses.

16.
Mol Plant Pathol ; 21(2): 218-229, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31747123

RESUMO

YajQ, a binding protein of the universal bacterial second messenger cyclic di-GMP (c-di-GMP), affects virulence in several bacterial pathogens, including Xanthomonas campestris. In this bacterium, YajQ interacts with the transcription factor LysR. Upon c-di-GMP binding, the whole c-di-GMP-YajQ-LysR complex is found to dissociate from DNA, resulting in virulence gene regulation. Here, we identify a YajQ-LysR-like system in the bacterial biocontrol agent Lysobacter enzymogenes OH11 that secretes an antifungal antibiotic, heat-stable antifungal factor (HSAF) against crop fungal pathogens. We show that the YajQ homologue, CdgL (c-di-GMP receptor interacting with LysR) affects expression of the HSAF biosynthesis operon by interacting with the transcription activator LysR. The CdgL-LysR interaction enhances the apparent affinity of LysR to the promoter region upstream of the HSAF biosynthesis operon, which increases operon expression. Unlike the homologues CdgL (YajQ)-LysR system in X. campestris, we show that c-di-GMP binding to CdgL seems to weaken CdgL-LysR interactions and promote the release of CdgL from the LysR-DNA complex, which leads to decreased expression. Together, this study takes the YajQ-LysR-like system from bacterial pathogens to a crop-protecting bacterium that is able to regulate antifungal HSAF biosynthesis via disassembly of the c-di-GMP receptor-transcription activator complex.

17.
Sci Total Environ ; 707: 136106, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31863990

RESUMO

Aerobic granular sludge (AGS) could be cultivated from only flocs (called normal granulation (NG) process) or mixture of flocs and crushed AGS (called enhanced granulation (EG) process), which might lead to different system performances such as granulation speed and pollutants removal efficiencies. However, the differences of mechanisms between NG and EG processes at microbial community level are still unknown. In this study, the NG and EG processes were implemented successively in a pilot-scale sequencing batch reactor (SBR) with certain amounts of additional carbon sources. Illumina MiSeq sequencing and quantitative PCR were applied to investigate the dynamics of bacterial communities during NG and EG processes and explore the possible explanations for faster EG process. The results showed that significant distinctions in bacterial diversities and community structures were observed between NG and EG processes. The major contributor to NG process was bacterial communities with 32.04% contribution. While EG process was more dependent on the interactions (73.16% contribution) between the bacterial communities and environmental variables (operational parameters and self-adaptive variable). EG process had higher relative abundances of functional bacteria than NG process. Glycogen accumulating organisms (GAOs) related bacteria with a total relative abundance of maximum 65.43% might be mainly responsible for the faster EG process. This study provided microbial insights for practical application of AGS technology that inoculating crushed AGS might be an effective way to cultivate AGS.

18.
J Ethnopharmacol ; 248: 112302, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31614203

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The pregnane-X-receptor (PXR) is involved in inflammatory bowel disease (IBD). Patchouli alcohol (PA) has anti-inflammatory effects; however, the effect of PA on IBD pathogenesis remains largely unknown. AIM OF THE STUDY: The aim of the present study was to investigate the anti-inflammatory effect of PA, primarily focused on crosstalk between PA-mediated PXR activation and NF-κB inhibition. MATERIALS AND METHODS: We evaluated the anti-inflammatory effect of PA with respect to PXR/NF-κB signalling using in vitro and in vivo models. In vitro, PA, identified as a PXR agonist, was evaluated by hPXR transactivation assays and through assessing for CYP3A4 expression and activity. NF-κB inhibition was analysed based on NF-κB luciferase assays, NF-κB-mediated pro-inflammatory gene expression, and NF-κB nuclear translocation after activation of PXR by PA. In vivo, colonic mPXR and NF-κB signalling were analysed to assess PA-mediated the protective effect against dextran sulphate sodium (DSS)-induced colitis. Furthermore, pharmacological inhibition of PXR was further evaluated by examining PA protection against DSS-induced colitis. RESULTS: PA induced CYP3A4 expression and activity via an hPXR-dependent mechanism. PA-mediated PXR activation attenuated inflammation by inhibiting NF-κB activity and nuclear translocation. The anti-inflammatory effect of PA on NF-κB was abolished by PXR knockdown. PA prevented DSS-induced inflammation by regulating PXR/NF-κB signalling, whereas pharmacological PXR inhibition abated PA-mediated suppressive effects on NF-κB inflammation signalling. CONCLUSIONS: PA activates PXR signalling and suppresses NF-κB signalling, consequently causing amelioration of inflammation. Our results highlight the importance of PXR-NF-κB crosstalk in colitis and suggest a novel therapeutic reagent.

19.
Drug Deliv ; 27(1): 66-80, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858838

RESUMO

A series of multifunctional compounds (MFCs) 1a-1e based on 1,8-naphthalimide and [12]aneN3 building blocks were designed and synthesized. They were used as not only fluorescent probes for recognition of Cu2+ ions but also as non-viral gene vectors for DNA and RNA delivery. Furthermore, their complexes with Cu2+ (1-Cu) could also selectively stain lysosome in HeLa cells. In order to achieve high performance multifunctional materials, structure-performance relationship of MFCs 1a-1e was studied. It was found that MFCs 1a-1e exhibited highly selective fluorescence turn-off for Cu2+, without interference by other metal ions in aqueous solution. The fluorescence emission of 1a-1e was quenched by a factor of 10-fold, 47-fold, 6-fold, 64-fold, and 15-fold respectively in the presence of Cu2+ ions. Due to high sensitivity, good water solubility, and low cytotoxicity, MFCs 1a-1d were successfully applied in the recognition of Cu2+ and selectively staining lysosome in HeLa cells. Most importantly, MFCs 1a and 1b had excellent HeLa cell selectivity in RNA delivery, and their performances were far better than lipofectamine 2000 and 25 kDa PEI.

20.
Proc Natl Acad Sci U S A ; 117(1): 381-387, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31848241

RESUMO

The vast majority of biological carbon dioxide fixation relies on the function of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). In most cases the enzyme exhibits a tendency to become inhibited by its substrate RuBP and other sugar phosphates. The inhibition is counteracted by diverse molecular chaperones known as Rubisco activases (Rcas). In some chemoautotrophic bacteria, the CbbQO-type Rca Q2O2 repairs inhibited active sites of hexameric form II Rubisco. The 2.2-Å crystal structure of the MoxR AAA+ protein CbbQ2 from Acidithiobacillus ferrooxidans reveals the helix 2 insert (H2I) that is critical for Rca function and forms the axial pore of the CbbQ hexamer. Negative-stain electron microscopy shows that the essential CbbO adaptor protein binds to the conserved, concave side of the CbbQ2 hexamer. Site-directed mutagenesis supports a model in which adenosine 5'-triphosphate (ATP)-powered movements of the H2I are transmitted to CbbO via the concave residue L85. The basal ATPase activity of Q2O2 Rca is repressed but strongly stimulated by inhibited Rubisco. The characterization of multiple variants where this repression is released indicates that binding of inhibited Rubisco to the C-terminal CbbO VWA domain initiates a signal toward the CbbQ active site that is propagated via elements that include the CbbQ α4-ß4 loop, pore loop 1, and the presensor 1-ß hairpin (PS1-ßH). Detailed mechanistic insights into the enzyme repair chaperones of the highly diverse CO2 fixation machinery of Proteobacteria will facilitate their successful implementation in synthetic biology ventures.

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