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1.
Sci Total Environ ; 914: 169595, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38154649

ABSTRACT

Municipal solid waste incineration fly ash (MSWI FA) is a kind of hazardous waste that contains a substantial amount of heavy metals. To facilitate the appropriate treatment of MSWI FA, the leaching behavior of heavy metals was evaluated in MSWI FA from various sources using different leaching methods. Nine kinds of MSWI FA were investigated using three kinds of batch leaching tests (TCLP, HJ/T 300, and EN12457-2). The chemical form distributions of heavy metals in MSWI FA were obtained by sequential extraction procedures (SEPs) and the environmental risk posed by MSWI FA was comprehensively evaluated. The results showed that the grate and fluidized bed MSWI FA performed differently in various leaching methods, which was mainly dependent on the leachate pH and the chemical form distributions of the heavy metals. In addition, the BCR SEP was more suitable for the fractionation of heavy metals and the environmental risk assessment of MSWI FA when compared with Tessier's SEP. The overall pollution toxicity index allowed a comprehensive risk assessment specific to the leaching environment, thereby offering valuable guidelines for the stabilization or resource-based treatment of MSWI FA.

2.
Environ Sci Pollut Res Int ; 30(60): 125585-125595, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38006480

ABSTRACT

Municipal solid waste incinerator (MSWI) fly ash poses intricate compositional challenges and potential environmental hazards. Effective management of such hazardous waste is imperative to mitigate the release of toxic compounds into the environment. Solidification/stabilization (S/S) processes have emerged as a viable strategy to transform MSWI fly ash from incineration waste into a safer and more environmentally benign material. This study aims to comprehensively investigate the potential of utilizing cow bone waste to stabilize heavy metals, focusing on Pb, within municipal solid waste incineration fly ash. Experimental investigations encompassed cow bone-to-fly ash weight ratios ranging from 0.0 (control group) to 7:3, a settling time of 2 h, and a liquid-to-solid (L/S) ratio of 1.0 mL/g. Cow bone waste exhibited pronounced efficacy, particularly within the short settling time, yielding a remarkable Pb removal efficiency of up to 99% at a cow bone waste dose of merely 2% and an L/S ratio of 1.0 mL/g. Concurrently, other heavy metals such as Cd, Cu, and Zn were effectively stabilized with a cow bone waste dose of 1.5% during the same 2-h settling period. The results underscore the pivotal roles of ash/bone ratio and settling time in augmenting Pb stabilization in MSWI fly ash. The application of cow bone waste is anticipated to offer a cost-effective and environmentally sound approach, aligning with sustainable waste management principles.


Subject(s)
Metals, Heavy , Refuse Disposal , Coal Ash , Solid Waste , Refuse Disposal/methods , Particulate Matter , Lead , Carbon , Incineration , Metals, Heavy/analysis
3.
EMBO Rep ; 24(11): e56864, 2023 11 06.
Article in English | MEDLINE | ID: mdl-37575008

ABSTRACT

Kinesin-driven intracellular transport is essential for various cell biological events and thus plays a crucial role in many pathological processes. However, little is known about the molecular basis of the specific and dynamic cargo-binding mechanism of kinesins. Here, an integrated structural analysis of the KIF3/KAP3 and KIF3/KAP3-APC complexes unveils the mechanism by which KIF3/KAP3 can dynamically grasp APC in a two-step manner, which suggests kinesin-cargo recognition dynamics composed of cargo loading, locking, and release. Our finding is the first demonstration of the two-step cargo recognition and stabilization mechanism of kinesins, which provides novel insights into the intracellular trafficking machinery.


Subject(s)
Cell Communication , Kinesins , Kinesins/metabolism , Biological Transport , Microtubules/metabolism
4.
Cell Mol Biol (Noisy-le-grand) ; 69(4): 147-151, 2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37329533

ABSTRACT

This study aimed to investigate the relationship between MMP-2, TIMP-1, ß2-MG, hs-CRP and the progression of type 2 diabetic retinopathy (T2DM). For this purpose, 68 patients with T2DM retinopathy treated in our hospital were selected as the retinopathy group (REG), and 68 T2DM patients without retinopathy were selected as the control group (CDG). The serum levels of MMP-2, TIMP-1, ß2-MG and hs-CRP were compared between the two groups. According to the international clinical classification of T2DM non-retinopathy (NDR), the patients were divided into non-proliferative T2DM retinopathy group (NPDR) (n=28) and proliferative T2DM retinopathy group (PDR) (n=40). The levels of MMP-2, TIMP-1, ß2-MG and hs-CRP in patients with different conditions were compared. In addition, the Spearman method was used to analyze the correlation between the levels of MMP-2, TIMP-1, ß2-MG, hs-CRP and glucose and lipid metabolism and the course of disease in patients with T2DM retinopathy (DR). Logistic multiple regression was used to analyze the risk factors of DR. Results showed that the levels of serum MMP-2, ß2-MG and hs-CRP in PDR groups were raised than those in NPDR and NDR, while the serum TIMP-1 level was reduced. The levels of MMP-2, ß2-MG and hs-CRP were positively correlated with the levels of HbA1c, TG and the course of disease in DR patients, while the levels of TIMP-1 in DR patients were negatively correlated with the levels of HbA1c, TG and the course of disease. The results of multivariate Logistic regression model showed that MMP-2, ß2-MG and hs-CRP were independent risk factors for DR, and TIMP-1 was the protective factor for DR. In conclusion, the changes of peripheral blood MMP-2, TIMP-1, hs-CRP and ß2-MG levels are closely related to the progression of T2DM retinopathy.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , C-Reactive Protein/metabolism , Glycated Hemoglobin , Tissue Inhibitor of Metalloproteinase-1 , Matrix Metalloproteinase 2
5.
Environ Res ; 218: 114873, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36504006

ABSTRACT

The disposal of hazardous municipal solid waste incineration (MSWI) fly ash is a challenge nowadays. Recently, the re-utilization of MSWI fly ash by converting it to useful zeolite-containing materials has attracted attention. However, the zeolitic products fabricated from MSWI fly ash are usually of low quality and rarely reported to be applied for photocatalysis. In this study, valuable zeolites (e.g., NaP1) are synthesized from MSWI fly ash via a modified microwave-assisted hydrothermal method. The key parameters for the hydrothermal method including temperature, duration, the amount of additive, and water volume, are investigated and optimized. Specifically, increasing the hydrothermal temperature can promote the synthesis of zeolitic materials; a relatively long hydrothermal duration is essential to accomplish the assembly of zeolites; the addition of Na2SiO3 can increase the precursor for the fabrication of zeolites; the water volume makes little influence on the crystal style of products. Eventually, the hydrothermal condition of 180 °C, 1 h, 0.5 g Na2SiO3, and 10 mL water is suggested based on the energy consumption and the quality of zeolites. The product containing zeolite NaP1 from such a condition is further applied to degrade methylene blue by photocatalysis. The removal rate has reached 96% within 12 h, which dramatically surpasses that of the raw fly ash (38%). Such excellent photocatalytic performance is attributed to the 10-fold increased surface area (24.864 m2 g-1) and active metal elements embedding in the zeolite structures.


Subject(s)
Metals, Heavy , Refuse Disposal , Zeolites , Incineration , Coal Ash , Solid Waste , Zeolites/chemistry , Refuse Disposal/methods , Methylene Blue , Metals, Heavy/analysis , Carbon/chemistry , Particulate Matter/chemistry
6.
Sci Total Environ ; 855: 158741, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36115393

ABSTRACT

The Si and Al in municipal solid waste incineration fly ash (MSWI FA) can be utilized for zeolite fabrication, which can improve the application value of the products. This study focuses on the fabrication of zeolite from MSWI FA by microwave-assisted hydrothermal (MH) treatment. The effects of magnetic stirring time, Na2SiO3 dosage, MH time, and NaOH solution concentration on the crystallization of zeolite NaP1 from MSWI FA are systematically analyzed. The synthetic products are analyzed through spectroscopic and mineralogical methods. The results show that zeolite NaP1 with high crystallinity (51.68 %) can be fabricated by magnetic stirring and MH treatment, and the cation exchange capacity (CEC) of the product can reach a value of 2.58 meq/g, which is approximately 133 times that of the CEC of MSWI FA. The Si/Al ratio plays a decisive role in the zeolite NaP1 synthesis, and a Na2SiO3 dosage of 30 wt% is adopted for zeolite NaP1 fabrication. A NaOH concentration of 1 M is sufficient for zeolite NaP1 synthesis. Additionally, the zeolite NaP1 content is found to obviously increase with increasing MH time from 0.5 h to 2 h. To demonstrate the feasibility of the method provided in this study, the optimal experimental condition is employed for various MSWI FAs, and zeolite NaP1 and analcime are fabricated successfully. The leachability of heavy metals for the synthetic products was evaluated, which met the requirements for pollution control. The BET surface area and total pore volume of zeolite NaP1 fabricated at optimal condition are 61.42 m2/g and 0.44 cm3/g, respectively. The adsorption capacity of zeolite NaP1 for Cu2+ ion and methylene blue are determined to be 84.65 mg/g and 84.55 mg/g, respectively, indicating zeolite NaP1 is a potential adsorbent for cation ion and dyes. This study provides an environmentally friendly scheme for the utilization of MSWI FA.


Subject(s)
Metals, Heavy , Refuse Disposal , Zeolites , Incineration , Coal Ash/chemistry , Solid Waste/analysis , Adsorption , Microwaves , Sodium Hydroxide , Carbon/chemistry , Metals, Heavy/analysis , Refuse Disposal/methods , Particulate Matter/chemistry
7.
Sci Total Environ ; 854: 158594, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36116667

ABSTRACT

Municipal solid waste incineration fly ash (MSWI FA) is categorized as a hazardous waste, which demands environmentally acceptable treatment due to its easy leachability toxic of heavy metals. This study investigated an innovative and improved method for stabilization/solidification (S/S) of MSWI FA with coal gangue based geopolymer by the addition of active calcium content. The specimen with addition of calcium oxide up to 10 % reached the compressive strength of 2.14 MPa at 28 d. The addition of 30 % calcium oxide resulted in the highest immobilization efficiencies of Cd (98.96 %) and Pb (99.19 %). X-ray Diffraction (XRD), Fourier Transform Infrared Spectrometry (FTIR), Scanning Electron Microscope (SEM), and thermogravimetric (TG) analysis indicated the generation of calcium-containing hydration products was promoted after the improvement of calcium content in binder. Heavy metals were stabilized through the chemical adsorption and ions exchange of amorphous hydration products. On the whole, this study illustrated that the incorporation of active calcium content can improve efficiently S/S of hazardous ash waste such as MSWI FA.

8.
Cell Mol Biol (Noisy-le-grand) ; 68(6): 92-97, 2022 Jun 30.
Article in English | MEDLINE | ID: mdl-36227671

ABSTRACT

The study aimed to investigate the influence of heme oxygenase-1 (HO-1) on rats with diabetic retinopathy (DR) through the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. 40 rats were selected and divided into Control group (n=10), diabetes mellitus (DM) group (n=10), cobalt protoporphyrin (CoPP) group (n=10) and zinc protoporphyrin (ZnPP) group (n=10) according to weight. Streptozotocin (STZ) was intraperitoneally injected to establish the DM model in DM, CoPP and ZnPP groups, and CoPP and ZnPP solution was intraperitoneally injected in CoPP and ZnPP groups, respectively. Blood was drawn to determine fasting blood glucose. The changes in the protein and messenger ribonucleic acid (mRNA) levels were evaluated via Western blotting and polymerase chain reaction (qRT-PCR), respectively. Enzyme-linked immunosorbent assay (ELISA) was performed to measure antioxidant capacity and the levels of total reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GPx). The weight of rats was notably higher in the CoPP group and lower inZnPP group than in the DM group (p<0.05). After induction of DM, compared with those in the DM group, the protein expression levels of Nrf2 and pERK were considerably elevated in the CoPP group (p<0.05) but declined remarkably in the ZnPP group (p<0.05). The levels of total ROS and MDA were notably elevated (p<0.05) in DM and ZnPP groups, with a lowered level of GPx and distinctly elevated levels of MDA and total ROS (p<0.05). Moreover, the mRNA expression level of HO-1 in the retinas of rats was remarkably raised in the DM group and CoPP group (p<0.05), but it declined markedly in the ZnPP group (p<0.05). The red fluorescent aggregation of Nrf2 and pERK proteins was overtly less in the ZnPP group than that in the DM group (p<0.05). HO-1 can affect the level of oxidative stress and intervene in retinopathy in DM rats through the Nrf2/ERK pathway.


Subject(s)
Diabetic Retinopathy , Heme Oxygenase-1 , Animals , Antioxidants/metabolism , Blood Glucose , Extracellular Signal-Regulated MAP Kinases/metabolism , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Heme Oxygenase (Decyclizing)/genetics , Heme Oxygenase (Decyclizing)/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , MAP Kinase Signaling System , Malondialdehyde , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species , Signal Transduction , Streptozocin
9.
Proc Natl Acad Sci U S A ; 119(34): e2207134119, 2022 08 23.
Article in English | MEDLINE | ID: mdl-35969738

ABSTRACT

Cilia are microtubule-based organelles that power cell motility and regulate sensation and signaling, and abnormal ciliary structure and function cause various ciliopathies. Cilium formation and maintenance requires intraflagellar transport (IFT), during which the kinesin-2 family motor proteins ferry IFT particles carrying axonemal precursors such as tubulins into cilia. Tubulin dimers are loaded to IFT machinery through an interaction between tubulin and the IFT-74/81 module; however, little is known of how tubulins are unloaded when arriving at the ciliary tip. Here, we show that the ciliary kinase DYF-5/MAK phosphorylates multiple sites within the tubulin-binding module of IFT-74, reducing the tubulin-binding affinity of IFT-74/81 approximately sixfold. Ablation or constitutive activation of IFT-74 phosphorylation abnormally elongates or shortens sensory cilia in Caenorhabditis elegans neurons. We propose that DYF-5/MAK-dependent phosphorylation plays a fundamental role in ciliogenesis by regulating tubulin unloading.


Subject(s)
Caenorhabditis elegans/metabolism , Cilia , Mitogen-Activated Protein Kinases/metabolism , Animals , Caenorhabditis elegans Proteins/metabolism , Cilia/metabolism , Phosphorylation , Tubulin/metabolism
10.
Sci Total Environ ; 851(Pt 1): 158182, 2022 Dec 10.
Article in English | MEDLINE | ID: mdl-35995162

ABSTRACT

Fly ash is an incineration byproduct of thermal power plants. Due to the complex composition of fly ash, improper disposal will seriously harm the ecological environment. Therefore, how to effectively use fly ash to safely and environmentally replace landfills is a worldwide concern. Considering the high silicon and aluminum contents in fly ash, it has the potential to synthesize zeolite, which has a wide range of applications in sewage treatment, gas adsorption, etc. Therefore, the synthesis of zeolites from fly ash is consistent with the theme of sustainable development. The synthesis mechanism of zeolite, various synthetic methods of zeolite from fly ash and their advantages and disadvantages was introduced in detail. In addition, combined with the current research hotspots, the application of synthetic zeolite from fly ash in the fields of sewage treatment and gas adsorption was introduced. Finally, the future development prospects and research directions of synthetic zeolite from fly ash to improve the utilization rate of fly ash were considered.


Subject(s)
Coal Ash , Zeolites , Aluminum , Sewage , Silicon
11.
Environ Pollut ; 311: 119878, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-35944780

ABSTRACT

Incineration has gradually become the most effective way to deal with MSW due to its obvious volume reduction and weight reduction effects. However, since heavy metals and organic pollutants carried by municipal solid waste incinerator fly ash (MSWI FA) pose a serious threat to the ecological environment and human health, they need to be handled carefully. In this study, the current status of MSWI FA disposal was first reviewed, and the harmless and resourceful disposal technologies of heavy metals and organic pollutants in MSWI FA are summarized as well. A summary of the advantages and disadvantages of each technology, including sintering, melting/vitrification, hydrothermal treatment, mechanochemistry, solidification/stabilization of MSWI FA, is compared. Finally, the research work that needs to be strengthened in the future (such as codisposal of multiple wastes, long-term stability research of disposal products, etc.) was proposed. Through comprehensive analysis, some reasonable and feasible suggestions were provided for the effective and safe disposal of MSWI FA in the future.


Subject(s)
Dioxins , Environmental Pollutants , Metals, Heavy , Refuse Disposal , Carbon , Coal Ash , Humans , Incineration , Metals, Heavy/analysis , Particulate Matter , Solid Waste/analysis , Technology
12.
ACS Omega ; 7(27): 23929-23938, 2022 Jul 12.
Article in English | MEDLINE | ID: mdl-35847277

ABSTRACT

Severe corrosion to superheater tubes at high temperatures was gained virtually by gaseous corrosion media, such as HCl and SO2, in the municipal solid waste incineration flue gas. To clarify the effect of varying concentrations of HCl and SO2 in the oxidizing atmosphere on the corrosion of 12Cr1MoV, a commercial alloy used in superheaters, two series of corrosion tests under simulated flue gas were performed. Both the corrosion kinetics and corrosion morphology were measured in this work. The results of the present study demonstrated that the addition of HCl was more corrosive than that of SO2 under an oxidizing atmosphere. The increased HCl concentration had an accelerating effect on the corrosion rate, but the relation between the two was not linear. In contrast, SO2 exhibited a negligible or even inhibitory effect on corrosion. Both series of test results consistently proved that the temperature had a significant influence on the corrosion of 12Cr1MoV alloy, in particular at 580 °C.

13.
PLoS Genet ; 18(6): e1010223, 2022 06.
Article in English | MEDLINE | ID: mdl-35679337

ABSTRACT

Oncohistone mutations are crucial drivers for tumorigenesis, but how a living organism governs the loss-of-function oncohistone remains unclear. We generated a histone H2B triple knockout (3KO) strain in Caenorhabditis elegans, which decreased the embryonic H2B, disrupted cell divisions, and caused animal sterility. By performing genetic suppressor screens, we uncovered that mutations defective in the histone H3-H4 chaperone UNC-85 restored H2B 3KO fertility by decreasing chromatin H3-H4 levels. RNA interference of other H3-H4 chaperones or H3 or H4 histones also rescued H2B 3KO sterility. We showed that blocking H3-H4 chaperones recovered cell division in C. elegans carrying the oncohistone H2BE74K mutation that distorts the H2B-H4 interface and induces nucleosome instability. Our results indicate that reducing chromatin H3-H4 rescues the dysfunctional H2B in vivo and suggest that inhibiting H3-H4 chaperones may provide an effective therapeutic strategy for treating cancers resulting from loss-of-function H2B oncohistone.


Subject(s)
Histones , Infertility , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Chromatin/genetics , Histone Chaperones/genetics , Histones/genetics , Histones/metabolism , Nucleosomes
14.
Exp Ther Med ; 24(1): 481, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35761801

ABSTRACT

The present study revealed that palmitic acid (PA) treatment induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, which are involved in the progression of proliferative vitreoretinopathy (PVR). ARPE-19 cells were treated with PA followed by miRNA screening and EMT marker detection using qRT-PCR. Then, miR-124 mimic or inhibitor was transfected into ARPE-19 cells to explore the role of miR-124 on the EMT of ARPE-19 cells using transwell assay. The underlying mechanism of miRNA were predicted by bioinformatics method and confirmed by luciferase activity reporter assay. Furthermore, gain-of-function strategy was also used to explore the role of LIN7C in the EMT of ARPE-19 cells. The expression of miRNA or mRNA expression was determined by qRT-PCR and the protein expression was determined using western blot assay. The result presented that PA reduced the expression of E-cadherin/ZO-1 whilst increasing the expression of fibronectin/α-SMA. In addition, PA treatment enhanced the expression of microRNA (miR)-124 in ARPE-19 cells. Overexpression of miR-124 enhanced PA-induced upregulation of E-cadherin and ZO-1 expression and downregulation of fibronectin and α-SMA. Moreover, miR-124 mimic also enhanced the migration of ARPE-19 cells induced by PA treatment. Inversely, miR-124 inhibitor presented opposite effect on PA-induced EMT and cell migration in ARPE-19 cells. Luciferase activity reporter assay confirmed that Lin-7 homolog C (LIN7C) was a direct target of miR-124 in ARPE-19 cells. Overexpression of LIN7C was found to suppress the migration ability and expression of fibronectin and α-SMA, while increasing expression of E-cadherin and ZO-1; miR-124 mimic abrogated the inhibitive effect of LIN7C on the EMT of ARPE-19 cells and PA further enhanced this abolishment. Collectively, these findings suggest that miR-124/LIN7C can modulate EMT and cell migration in RPE cells, which may have therapeutic implications in the management of PVR diseases.

15.
Environ Sci Pollut Res Int ; 29(10): 15057-15067, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34625893

ABSTRACT

In this study, the long-term leaching behaviors of Cd, Cr, Cu, Ni, Pb, and Zn in municipal solid waste incineration (MSWI) fly ash samples from grate-type (GT) and circulating fluidized bed (CFB) incinerators were investigated and compared under the simulated landfill leachate corrosion scenario, which was determined to be more severe than the acid rain corrosion scenario. The total heavy metal contents showed increasing hierarchies of Ni

Subject(s)
Metals, Heavy , Refuse Disposal , Water Pollutants, Chemical , Carbon , Coal Ash/analysis , Corrosion , Incineration , Metals, Heavy/analysis , Particulate Matter , Solid Waste/analysis
17.
Cell Rep ; 35(2): 108971, 2021 04 13.
Article in English | MEDLINE | ID: mdl-33852848

ABSTRACT

In schizophrenia (SCZ), neurons in the brain tend to undergo gross morphological changes, but the related molecular mechanism remains largely elusive. Using Kif3b+/- mice as a model with SCZ-like behaviors, we found that a high-betaine diet can significantly alleviate schizophrenic traits related to neuronal morphogenesis and behaviors. According to a deficiency in the transport of collapsin response mediator protein 2 (CRMP2) by the KIF3 motor, we identified a significant reduction in lamellipodial dynamics in developing Kif3b+/- neurons as a cause of neurite hyperbranching. Betaine administration significantly decreases CRMP2 carbonylation, which enhances the F-actin bundling needed for proper lamellipodial dynamics and microtubule exclusion and may thus functionally compensate for KIF3 deficiency. Because the KIF3 expression levels tend to be downregulated in the human prefrontal cortex of the postmortem brains of SCZ patients, this mechanism may partly participate in human SCZ pathogenesis, which we hypothesize could be alleviated by betaine administration.


Subject(s)
Betaine/pharmacology , Intercellular Signaling Peptides and Proteins/genetics , Kinesins/genetics , Nerve Tissue Proteins/genetics , Neurons/drug effects , Prefrontal Cortex/drug effects , Pseudopodia/drug effects , Schizophrenia/diet therapy , Actins/genetics , Actins/metabolism , Animals , Behavior, Animal/drug effects , Biological Transport , Diet/methods , Disease Models, Animal , Gene Expression Regulation, Developmental , Humans , Intercellular Signaling Peptides and Proteins/deficiency , Kinesins/deficiency , Male , Mice , Mice, Knockout , Microtubules/drug effects , Microtubules/metabolism , Microtubules/ultrastructure , Nerve Tissue Proteins/deficiency , Neurons/metabolism , Neurons/ultrastructure , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Protein Binding , Protein Carbonylation , Pseudopodia/metabolism , Pseudopodia/ultrastructure , Schizophrenia/genetics , Schizophrenia/metabolism , Schizophrenia/pathology
18.
J Biol Chem ; 295(51): 17865-17876, 2020 12 18.
Article in English | MEDLINE | ID: mdl-33454020

ABSTRACT

Investigations of bacterial resistance strategies can aid in the development of new antimicrobial drugs as a countermeasure to the increasing worldwide prevalence of bacterial antibiotic resistance. One such strategy involves the TipA class of transcription factors, which constitute minimal autoregulated multidrug resistance (MDR) systems against diverse antibiotics. However, we have insufficient information regarding how antibiotic binding induces transcriptional activation to design molecules that could interfere with this process. To learn more, we determined the crystal structure of SkgA from Caulobacter crescentus as a representative TipA protein. We identified an unexpected spatial orientation and location of the antibiotic-binding TipAS effector domain in the apo state. We observed that the α6-α7 region of the TipAS domain, which is canonically responsible for forming the lid of antibiotic-binding cleft to tightly enclose the bound antibiotic, is involved in the dimeric interface and stabilized via interaction with the DNA-binding domain in the apo state. Further structural and biochemical analyses demonstrated that the unliganded TipAS domain sterically hinders promoter DNA binding but undergoes a remarkable conformational shift upon antibiotic binding to release this autoinhibition via a switch of its α6-α7 region. Hence, the promoters for MDR genes including tipA and RNA polymerases become available for transcription, enabling efficient antibiotic resistance. These insights into the molecular mechanism of activation of TipA proteins advance our understanding of TipA proteins, as well as bacterial MDR systems, and may provide important clues to block bacterial resistance.


Subject(s)
Anti-Bacterial Agents/metabolism , Bacterial Proteins/metabolism , Trans-Activators/metabolism , Amino Acid Sequence , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/chemistry , Caulobacter crescentus/metabolism , Crystallography, X-Ray , DNA/chemistry , DNA/metabolism , Dimerization , Drug Resistance, Multiple, Bacterial/genetics , Kinetics , Promoter Regions, Genetic , Protein Binding , Protein Conformation, alpha-Helical , Protein Structure, Tertiary , Sequence Alignment , Trans-Activators/antagonists & inhibitors , Trans-Activators/chemistry , Transcriptional Activation/drug effects
19.
FEBS J ; 287(11): 2292-2311, 2020 06.
Article in English | MEDLINE | ID: mdl-31725950

ABSTRACT

The eubacterial ß sliding clamp (DnaN) plays a crucial role in DNA metabolism through direct interactions with DNA, polymerases, and a variety of protein factors. A canonical protein-DnaN interaction has been identified in Escherichia coli and some other species, during which protein partners are tethered into the conserved canonical hydrophobic crevice of DnaN via the consensus ß-binding motif. Caulobacter crescentus is an excellent research model for use in the investigation of DNA replication and cell-cycle regulation due to its unique asymmetric cell division pattern with restricted replication initiation; however, little is known about the specific features of C. crescentus DnaN (CcDnaN). Here, we report a significant divergence in the association of CcDnaN with proteins based on docking analysis and crystal structures that show that the ß-binding motifs of its protein partners bind a novel pocket instead of the canonical site. Pull-down and isothermal titration calorimetry results revealed that mutations within the novel pocket disrupt protein-CcDnaN interactions. It was also shown by replication and regulatory inactivation of DnaA assays that mediation of protein interaction by the novel pocket is closely related to the performance of CcDnaN during replication and the DnaN-mediated regulation process. Moreover, assessments of clamp competition showed that DNA does not compete with protein partners when binding to the novel pocket. Overall, our structural and biochemical analyses provide strong evidence that CcDnaN employs a noncanonical protein association pattern.


Subject(s)
Caulobacter crescentus/genetics , DNA Replication/genetics , DNA-Binding Proteins/genetics , Transcription, Genetic , Caulobacter crescentus/growth & development , Escherichia coli/genetics , Escherichia coli Proteins/genetics , Gene Expression Regulation, Bacterial/genetics
20.
Waste Manag ; 102: 270-280, 2020 Feb 01.
Article in English | MEDLINE | ID: mdl-31698229

ABSTRACT

Solid recovered fuel (SRF) has the characteristics of high calorific value and low chlorine and mercury content. The thermal decomposition of SRF collected from a municipal solid waste (MSW) incineration power plant in Hangzhou was investigated in this study. The study exhibits far-reaching significance for the design and commercial operation of SRF pyrolysis facilities and circulating fluidized bed (CFB) power plants. The pyrolysis behavior of SRF and its sorted components was evaluated by thermogravimetric analysis (TG). Five heating rates of 10, 15, 20, 25 and 30 °C·min-1 were conducted to analyze the effect of heating rate. The interactive effect of the sorted components was discussed by comparing the experimental and theoretical curves. Furthermore, the kinetic parameters were determined by using the Coats-Redfern (CR), Kissinger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO) methods. The activation energies of SRF and its sorted components in the pyrolysis process were obtained. The main reaction stages of the SRF and its sorted components were described by different mechanism functions. However, it was found that the KAS and FWO methods were not applicable for SRF according to the comparison results. The results provide useful information for the design and commercial operation of SRF pyrolysis facilities and CFB power plants.


Subject(s)
Incineration , Solid Waste , Heating , Kinetics , Thermogravimetry
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