Publications by authors named "Wei Zhan"

126 Publications

Vectored Immunotherapeutics for Infectious Diseases: Can rAAVs Be The Game Changers for Fighting Transmissible Pathogens?

Front Immunol 2021 11;12:673699. Epub 2021 May 11.

Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, United States.

Conventional vaccinations and immunotherapies have encountered major roadblocks in preventing infectious diseases like HIV, influenza, and malaria. These challenges are due to the high genomic variation and immunomodulatory mechanisms inherent to these diseases. Passive transfer of broadly neutralizing antibodies may offer partial protection, but these treatments require repeated dosing. Some recombinant viral vectors, such as those based on lentiviruses and adeno-associated viruses (AAVs), can confer long-term transgene expression in the host after a single dose. Particularly, recombinant (r)AAVs have emerged as favorable vectors, given their high transduction efficiency, proven clinical efficacy, and low immunogenicity profiles. Hence, rAAVs are being explored to deliver recombinant antibodies to confer immunity against infections or to diminish the severity of disease. When used as a vaccination vector for the delivery of antigens, rAAVs enable synthesis of foreign proteins with the conformation and topology that resemble those of natural pathogens. However, technical hurdles like pre-existing immunity to the rAAV capsid and production of anti-drug antibodies can reduce the efficacy of rAAV-vectored immunotherapies. This review summarizes rAAV-based prophylactic and therapeutic strategies developed against infectious diseases that are currently being tested in pre-clinical and clinical studies. Technical challenges and potential solutions will also be discussed.
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http://dx.doi.org/10.3389/fimmu.2021.673699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144494PMC
May 2021

Novel Combinatorial MicroRNA-Binding Sites in AAV Vectors Synergistically Diminish Antigen Presentation and Transgene Immunity for Efficient and Stable Transduction.

Front Immunol 2021 28;12:674242. Epub 2021 Apr 28.

Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, United States.

Recombinant adeno-associated virus (rAAV) platforms hold promise for gene therapy but are undermined by the undesirable transduction of antigen presenting cells (APCs), which in turn can trigger host immunity towards rAAV-expressed transgene products. In light of recent adverse events in patients receiving high systemic AAV vector doses that were speculated to be related to host immune responses, development of strategies to mute innate and adaptive immunity is imperative. The use of miRNA binding sites (miR-BSs) to confer endogenous miRNA-mediated regulation to detarget transgene expression from APCs has shown promise for reducing transgene immunity. Studies have shown that designing miR-142BSs into rAAV1 vectors were able to repress costimulatory signals in dendritic cells (DCs), blunt the cytotoxic T cell response, and attenuate clearance of transduced muscle cells in mice to allow sustained transgene expression in myofibers with negligible anti-transgene IgG production. In this study, we screened individual and combinatorial miR-BS designs against 26 miRNAs that are abundantly expressed in APCs, but not in skeletal muscle. The highly immunogenic ovalbumin (OVA) transgene was used as a proxy for foreign antigens. screening in myoblasts, mouse DCs, and macrophages revealed that the combination of miR-142BS and miR-652-5pBS strongly mutes transgene expression in APCs but maintains high myoblast and myocyte expression. Importantly, rAAV1 vectors carrying this novel miR-142/652-5pBS cassette achieve higher transgene levels following intramuscular injections in mice than previous detargeting designs. The cassette strongly inhibits cytotoxic CTL activation and suppresses the Th17 response . Our approach, thus, advances the efficiency of miRNA-mediated detargeting to achieve synergistic reduction of transgene-specific immune responses and the development of safe and efficient delivery vehicles for gene therapy.
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http://dx.doi.org/10.3389/fimmu.2021.674242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113644PMC
April 2021

Irisin ameliorates endoplasmic reticulum stress and liver fibrosis through inhibiting PERK-mediated destabilization of HNRNPA1 in hepatic stellate cells.

Biol Chem 2021 May 20;402(6):703-715. Epub 2021 Jan 20.

Department of Pathophysiology, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang City550004, Guizhou Province, China.

Liver fibrosis is a common consequence of chronic liver diseases involved with the activation of hepatic stellate cells (HSCs) and endoplasmic reticulum (ER) stress. Irisin is a small polypeptide hormone that shows beneficial effects on metabolic disorders. The current study aimed to investigate the biological function of irisin on hepatic fibrosis. A mouse model of carbon tetrachloride (CCl)-induced hepatic fibrosis was established. CCl-treated mice showed elevated serum levels of AST and ALT, increased collagen accumulation, induced ER stress, and upregulated expressions of pro-fibrotic proteins in the liver compared to the controls. The administration of irisin, however, ameliorated CCl-induced hepatic fibrosis in both cultured HSCs and mice. PKR-like ER kinase (PERK) is a key component of the ER stress-associated signaling pathway. We found that irisin treatment improved the stability of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) via regulating the phosphorylation of PERK in mouse livers and isolated HSCs. Also, the knockdown of HNRNPA1 eliminated the hepatoprotective effects of irisin on hepatic fibrosis and ER stress. In summary, this study showed that irisin alleviated ER stress and hepatic fibrosis by inhibiting PERK-mediated HNRNPA1 destabilization, suggesting that irisin may represent a promising therapeutic strategy for patients with liver fibrosis.
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http://dx.doi.org/10.1515/hsz-2020-0251DOI Listing
May 2021

Electrolytic manganese residue-based cement for manganese ore pit backfilling: Performance and mechanism.

J Hazard Mater 2021 Jun 5;411:124941. Epub 2021 Jan 5.

School of Resource and Environmental Sciences, Wuhan University, Wuhan, PR China.

Slag backfilling with electrolytic manganese residue (EMR) is an economical and environmentally-friendly method. However, high ammonium-nitrogen and manganese ions in EMRs limit this practice. In this study, a method of highly efficient simultaneous stabilization/solidification of ultrafine EMR by making EMR-based cementitious material (named EMR-P) was proposed and tested via single-factor and response surface optimization experiments. Results show that the stabilization efficiency of NH and Mn were above 95%, and the unconfined compressive strength of the EMR-P was 18.85 MPa (megapascal = N/mm). The mechanistic study concluded that the soluble manganese sulfate and ammonium sulfate in EMR were converted into the insoluble precipitates of manganite (MnOOH), gypsum (CaSO), MnNHPO·HO, and struvite (MgNHPO∙6 HO), leading to the stabilization of NH and Mn in the EMR-P. Leaching tests of EMR-P indicated that NH, Mn, and others heavy metals in the leachate were within the permitted level of the GB/T8978-1996. The novelty of this study includes the addition of phosphate and magnesium ions to precipitate ammonium-nitrogen and the combination between calcium ions (from CaHPO∙2 HO) and sulfate (from the EMR) to form calcium sulfate to improve the stability and unconfined compressive strength of cementitious materials (EMR-P).
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http://dx.doi.org/10.1016/j.jhazmat.2020.124941DOI Listing
June 2021

In-situ loading synthesis of graphene supported PtCu nanocube and its high activity and stability for methanol oxidation reaction.

J Colloid Interface Sci 2021 Aug 24;595:107-117. Epub 2021 Mar 24.

College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China. Electronic address:

A perfect PtCu nanocube with partial hollow structure was prepared by hydrothermal reaction and its electrocatalytic methanol oxidation reaction (MOR) was studied. The appropriate concentration of shape-control additives KI and triblock pluronic copolymers, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) (P123) play crucial roles in the final product morphology. The PtCu nanocubes can be perfectly in situ immobilizedonto graphene under the action of P123 while the structure and cubic morphologyremain unchanged. The electrochemical tests suggest that the obtained PtCu nanocube (PtCu-NCb) exhibits better MOR activity and stability than PtCu hexagon nanosheet (PtCu-NSt), PtCu nanoellipsoid (PtCu-NEs) and commercial Pt/C in alkaline medium. When in situ immobilized onto graphene, the MOR catalytic activity and stability of PtCu cubes are further improved. The markedly enhanced electrocatalytic activity and durability maybe attributed to the special cubic morphology with partial hollow structure enclosed by highly efficient facet and the probably the synergistic effect of PtCu and intermediate state CuI decorated on the surface and graphene.
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http://dx.doi.org/10.1016/j.jcis.2021.03.129DOI Listing
August 2021

The chromosome-scale reference genome of safflower (Carthamus tinctorius) provides insights into linoleic acid and flavonoid biosynthesis.

Plant Biotechnol J 2021 Mar 25. Epub 2021 Mar 25.

Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.

Safflower (Carthamus tinctorius L.), a member of the Asteraceae, is a popular crop due to its high linoleic acid (LA) and flavonoid (such as hydroxysafflor yellow A) contents. Here, we report the first high-quality genome assembly (contig N50 of 21.23 Mb) for the 12 pseudochromosomes of safflower using single-molecule real-time sequencing, Hi-C mapping technologies and a genetic linkage map. Phyloge nomic analysis showed that safflower diverged from artichoke (Cynara cardunculus) and sunflower (Helianthus annuus) approximately 30.7 and 60.5 million years ago, respectively. Comparative genomic analyses revealed that uniquely expanded gene families in safflower were enriched for those predicted to be involved in lipid metabolism and transport and abscisic acid signalling. Notably, the fatty acid desaturase 2 (FAD2) and chalcone synthase (CHS) families, which function in the LA and flavonoid biosynthesis pathways, respectively, were expanded via tandem duplications in safflower. CarFAD2-12 was specifically expressed in seeds and was vital for high-LA content in seeds, while tandemly duplicated CarFAD2 genes were up-regulated in ovaries compared to CarFAD2-12, which indicates regulatory divergence of FAD2 in seeds and ovaries. CarCHS1, CarCHS4 and tandem-duplicated CarCHS5~CarCHS6, which were up-regulated compared to other CarCHS members at early stages, contribute to the accumulation of major flavonoids in flowers. In addition, our data reveal multiple alternative splicing events in gene families related to fatty acid and flavonoid biosynthesis. Together, these results provide a high-quality reference genome and evolutionary insights into the molecular basis of fatty acid and flavonoid biosynthesis in safflower.
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http://dx.doi.org/10.1111/pbi.13586DOI Listing
March 2021

A New Method (Ball Milling and Sodium Sulfide) for Mechanochemical Treatment of Soda Ash Chromite Ore Processing Residue.

J Hazard Mater 2021 08 5;415:125601. Epub 2021 Mar 5.

Civil and Environmental Engineering Department, College of Engineering, University of Nebraska-Lincoln, Omaha, NE 68182, USA.

Hexavalent chromium in soda ash Chromite Ore Processing Residue (COPR) is harmful to the environment, it is imperative to develop a low cost, efficient, and effective treatment. Herein, a new method (ball milling+sodium sulfide) was developed for mechanochemical treatment of water-leached COPR (W-COPR, about 900 mg/kg non-exchangeble Cr(VI) and mostly chromite bounded). Under a stoichiometric ratio of S to Cr(VI) of 5, milling speed of 200 rpm, milling time of 30 min, ball-to-powder weight ratios of 8.5, and, a total Cr(VI) of 76.88 mg/kg and a Toxicity Characteristic Leaching Procedure (TCLP) total Cr value of 1.15 mg/L were achieved after treatment. Results of the mineral liberation analyser (MLA) analyses showed 10% increase of chromite grains liberation and grain size reduction were beneficial to the chromite-bound Cr(VI) reduction. Similar effects were also observed on magnesioferrite encapsulated Cr(VI). Particle aggregation and formation of glass phase colloid precipitation could potentially impede Cr(VI) reduction. Results of X-ray absorption near edge structure (XANES) analyses indicated that the treatment method reduced the actual Cr(VI) concentration to 312 mg/kg with Cr(VI) reduction efficiency of 98% being achieved. Overall, the new method is simple and efficient, and provides a guidance for future industrial application.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125601DOI Listing
August 2021

A Transient Hermaphroditic Stage in Early Male Gonadal Development in Little Yellow Croaker, .

Front Endocrinol (Lausanne) 2020 27;11:542942. Epub 2021 Jan 27.

Institute of Hydrobiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

Animal taxa show remarkable variability in sexual reproduction, where separate sexes, or gonochorism, is thought to have evolved from hermaphroditism for most cases. Hermaphroditism accounts for 5% in animals, and sequential hermaphroditism has been found in teleost. In this study, we characterized a novel form of the transient hermaphroditic stage in little yellow croaker () during early gonadal development. The ovary and testis were indistinguishable from 7 to 40 days post-hatching (dph). Morphological and histological examinations revealed an intersex stage of male gonads between 43 and 80 dph, which consist of germ cells, somatic cells, efferent duct, and early primary oocytes (EPOs). These EPOs in testis degenerate completely by 90 dph through apoptosis yet can be rescued by exogenous 17--estradiol. Male germ cells enter the mitotic flourishing stage before meiosis is initiated at 180 dph, and they undergo normal spermatogenesis to produce functional sperms. This transient hermaphroditic stage is male-specific, and the ovary development appears to be normal in females. This developmental pattern is not found in the sister species or any other closely related species. Further examinations of serum hormone levels indicate that the absence of 11-ketotestosterone and elevated levels of 17--estradiol delineate the male intersex gonad stage, providing mechanistic insights on this unique phenomenon. Our research is the first report on male-specific transient hermaphroditism and will advance the current understanding of fish reproductive biology. This unique gonadal development pattern can serve as a useful model for studying the evolutionary relationship between hermaphroditism and gonochorism, as well as teleost sex determination and differentiation strategies.
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http://dx.doi.org/10.3389/fendo.2020.542942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873647PMC
May 2021

LncRNA EWSAT1 Promotes Colorectal Cancer Progression Through Sponging miR-326 to Modulate FBXL20 Expression.

Onco Targets Ther 2021 13;14:367-378. Epub 2021 Jan 13.

Department of Traditional Chinese Medicine, Guizhou Provincial People's Hospital, Guiyang, People's Republic of China.

Background: Ewing sarcoma-associated transcript 1 () has been reported to be a pivotal modulator in a series of cancers. However, the function of in colorectal cancer (CRC) has not been elaborated. This study aimed to explore the role of in CRC progression and the underlying mechanisms.

Methods: The expression patterns of , and were examined by qCRCR. Si-EWSAT1 was transfected to study the effects of on cell proliferation and metastasis. Rescue experiments were performed to investigate the underlying mechanisms in vitro. Xenograft models were used to evaluate the role of in vivo.

Results: We found that was highly expressed in CRC tissues and cell lines and associated with poor overall survival. In vitro, knockdown of suppressed the cell proliferation, migration and invasion. Moreover, miR-326 was found to be a target of , and inhibitor could partially reverse the effects on CRC cell progression induced by si-EWSAT1. Subsequently, we validated as a vital downstream target for , and positively regulated via in vitro. In addition, these findings were confirmed by in vivo experiments.

Conclusion: Taken together, the data showed that promoted CRC progression via targeting pathway, which might provide a novel therapeutic target for CRC treatment.
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http://dx.doi.org/10.2147/OTT.S272895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812937PMC
January 2021

Leucine-rich Repeats and Immunoglobulin 1 (LRIG1) Ameliorates Liver Fibrosis and Hepatic Stellate Cell Activation via Inhibiting Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P) Pathway.

Iran J Allergy Asthma Immunol 2020 Aug 25;19(4):397-408. Epub 2020 Aug 25.

Department of Traditional Chinese Medicine, Guizhou Provincial People's Hospital, Guiyang, China.

To detect the leucine-rich repeats and immunoglobulin 1 (LRIG1) ameliorated liver fibrosis and hepatic stellate cell (HSC) activation via inhibiting sphingosine kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P) pathway. C57BL/6 male mice (eight weeks old) were intraperitoneal injection with 10% carbon tetrachloride (CCl4) as an in vivo model. The LX-2 cells were induced as amodel for in vitro study by TGF-β (10 ng/mL). The Hematoxylin-eosin (HE) staining, Masson staining, and Sirius red staining results showed that CCl4 caused serious fibrosis and injury in liver tissue, high expression of type I collagen α1 chain (Col1α1) and α-smooth muscle actin (α-SMA) in liver tissue, while the LRIG1 expression level was significantly decreased in LX-2 cell lines. The LRIG1 ameliorated CCl4-induced liver fibrosis, indicated by the fibronectin, α-SMA, LRIG1, SphK1, Col1α1, fibrin Connexin 1 (Fn1), tissue inhibitor of metalloproteinase-1 (TIMP1), sphingosine-1-phosphate (S1P), transforming growth factor-beta 1 (TGF-β1) expression level changes. Similar results were observed in TGF-β1 treated of LX-2 cells. However, the effects were attenuated by treatment with LRIG1. Moreover, SphK1 inhibitors abrogated the effect of LRIG1 on fibrosis. These results demonstrated that LRIG1 improved liver fibrosis in vitro and in vivo via suppressing the SphK1/S1P pathway, indicating its potential use in the treatment of liver fibrosis.
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http://dx.doi.org/10.18502/ijaai.v19i4.4114DOI Listing
August 2020

Blurred Electrode for Low Contact Resistance in Coplanar Organic Transistors.

ACS Nano 2021 Jan 18;15(1):1155-1166. Epub 2020 Dec 18.

Center for Advanced Optoelectronic Functional Materials Research, and Key Lab of UV-Emitting Materials and Technology of Ministry of Education, Northeast Normal University, 5268 Renmin Street, Changchun 130024, China.

Inefficient charge injection and transport across the electrode/semiconductor contact edge severely limits the device performance of coplanar organic thin-film transistors (OTFTs). To date, various approaches have been implemented to address the adverse contact problems of coplanar OTFTs. However, these approaches mainly focused on reducing the injection resistance and failed to effectively lower the access resistance. Here, we demonstrate a facile strategy by utilizing the blurring effect during the deposition of metal electrodes, to significantly reduce the access resistance. We find that the transition region formed by the blurring behavior can continuously tune the molecular packing and thin-film growth of organic semiconductors across the contact edge, as well as provide continuously distributed gap states for carrier tunnelling. Based on this versatile strategy, the fabricated dinaphtho[2,3-:2',3'-]thieno[3,2-]thiophene (DNTT) coplanar OTFT shows a high field-effect mobility of 6.08 cm V s and a low contact resistance of 2.32 kΩ cm, comparable to the staggered OTFTs fabricated simultaneously. Our work addresses the crucial impediments for further reducing the contact resistance in coplanar OTFTs, which represents a significant step of contact injection engineering in organic devices.
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http://dx.doi.org/10.1021/acsnano.0c08122DOI Listing
January 2021

Influence of two functional dextrins on the gel properties of kappa-carrageenan.

Food Res Int 2020 12 18;138(Pt A):109666. Epub 2020 Sep 18.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China; School of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China.

The physicochemical properties of κ-carrageenan (KC) can be improved by incorporation with small-molecule cosolvents. The texture and rheological properties, micromorphology, and crystallinity of KC incorporating indigestible dextrin (IDD) and beta-limit dextrin (BLD) were investigated. The rheological properties and sol-gel transition temperatures of the gels were slightly improved and the hardness of KC gels was significantly increased after the two dextrins were mixed in. Fourier transform infrared spectroscopy results indicated hydrogen-bonding interactions were strengthened in the presence of the dextrins. Confocal laser scanning microscope images revealed that a more homogenous structure was formed of the KC gel after the addition of dextrins. Moreover, X-ray diffraction patterns indicated the crystallinity of KC gel decreased upon dextrin addition. At the same dextrin content, IDD exerted a greater influence than BLD. IDD contents exceeding 3% (w/w) led to undesirable effects, whereas up to 5% (w/w) of BLD could be added. The two dextrins affected the rearrangement of the KC random coils in the sol state, and facilitated aggregation of the KC chains during cooling to form gel network structures after gelation. Therefore, the appropriate addition of these two dextrins can improve the texture and stability of KC gels and expand their application in functional foods.
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http://dx.doi.org/10.1016/j.foodres.2020.109666DOI Listing
December 2020

Rapid Access to Giant Unilamellar Liposomes with Upper Size Control: Membrane-Gated, Gel-Assisted Lipid Hydration.

Langmuir 2020 11 30;36(44):13193-13200. Epub 2020 Oct 30.

Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, United States.

Combining gel-assisted lipid hydration with membrane-based lipid extrusion, we demonstrate here a general procedure for rapid preparation of giant unilamellar liposomes with upper size control. Featured in this procedure are planar lipid stacks deposited on poly(vinyl alcohol) gel, which are further laminated atop with microporous polycarbonate membranes. Control of liposome size is thus realized through the uniform-sized pores of the latter, which provide the only access for the underlying lipids to enter the main aqueous phase upon hydration. Production of both single-phased and biphasic (Janus) liposomes using several commonly employed model lipids, including 1,2-dipalmitoyl--glycero-3-phosphocholine (DPPC), 1,2-dioleoyl--glycero-3-phosphocholine (DOPC), 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and cholesterol, is presented. The size distribution, yield and lamellarity of these liposome products are characterized and analyzed in detail by confocal fluorescence microscopy. This procedure thus offers a simple and fast alternative route to giant unilamellar liposomes with upper size control.
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http://dx.doi.org/10.1021/acs.langmuir.0c01496DOI Listing
November 2020

Mechanical behavior and dynamic damage constitutive model of glass fiber-reinforced Vinyl Ester with different fiber contents.

Sci Prog 2020 Oct-Dec;103(4):36850420961610

School of Mechanical and Electrical Engineering, Anhui Jianzhu University, Hefei, China.

Glass fiber-reinforced plastics (GFRP) based on polymer materials are widely used in lightweight impac-resistant structure design. In the process of design and development, it is very important to clarify the mechanical behavior under dynamic load to improve the product performance. Therefore, in this paper, Quasi-stati and dynamic compression behaviors of unidirectional continuous glass fiber-reinforced vinyl ester (GF/VE) composites with five kinds of fiber contents in the fiber direction were measured by an electro-hydraulic servo experiment system and a split Hopkinson pressure bar, and damage evolution of the material is analyzed by observing the microstructure of the cross section of the material. Results show that: The content of glass fiber affects the wettability between fiber and matrix, and the failure mechanism of material at high strain rate; Under quasi-static conditions, higher glass fiber content yields greater failure strength; Under dynamic conditions, as glass fiber content increases, toughness decreases, and the peak stress first increases and then decreases. Finally, the nonlinear viscoelastic constitutive model with damage evolution is derived, which can be used to predict the impact resistance of new composite structures in the product development and design stage and reduce the development cycle.
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http://dx.doi.org/10.1177/0036850420961610DOI Listing
October 2020

Bio-leaching of manganese from electrolytic manganese slag by Microbacterium trichothecenolyticum Y1: Mechanism and characteristics of microbial metabolites.

Bioresour Technol 2021 Jan 11;319:124056. Epub 2020 Sep 11.

School of Resource and Environmental Sciences, Wuhan University, Wuhan, PR China.

The related microbial metabolomics on biological recovery of manganese (Mn) from Electrolytic Manganese Slag (EMS) has not been studied. This study aimed at open the door to the metabolic characteristics of microorganisms in leaching Mn from EMS by using waste molasses (WM) as carbon source. Results show Microbacterium trichothecenolyticum Y1 (Y1) could effectively leach Mn from EMS in combination with using waste molasses as carbon and energy sources. For the first time, Y1 was identified to be capable of generating and then metabolizing several organic acids or other organic matter (e.g., fumaric acid, succinic acid, malic acid, glyoxylic acid, 3-hydroxybutyric acid, glutaric acid, L(+)-tartaric acid, citric acid, tetrahydrofolic acid, and L-methionine). The production of organic acids by Y1 bacteria was promoted by EMS with the carbon source. This study demonstrated for the first time that metabolic characteristics and carbon source metabolic pathways of Y1 in bioleaching of Mn from EMS.
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http://dx.doi.org/10.1016/j.biortech.2020.124056DOI Listing
January 2021

An optofluidic conveyor for particle transportation based on a fiber array and photothermal convection.

Lab Chip 2020 10;20(21):4063-4070

Materials Science and Engineering School, Huazhong University of Science and Technology, Wuhan 430074, China.

In this paper, a thermal convection-based optofluidic conveyor has been introduced, which can flexibly capture and manipulate multiple 20-120 μm silica particles with utmost accuracy. Near the end face, a fiber-based light source can confine 100 μm silica particles within 100 microns. By switching the light source of the fiber array, centimeter-range transportation of 100 μm SiO2 particles has been successfully achieved, which was not possible in optical trapping devices as we know. Through the comparative experiment with silica, polystyrene, and zirconium dioxide particles, the presented conveyor system is proved to be independent of the particles' dielectric properties. Moreover, sorting of silica and polystyrene particles based on the difference of mass densities has also been achieved. Additionally, the components of this conveyor (fiber array) and chip parts (microfluidic chamber) are freely detachable. Here, instead of expensive laser systems, a non-coherent light source has been utilized, which eventually eliminates the use of optical lens assemblies. All these features lead to making the equipment extremely simple in structure and low in cost. Besides, this optofluidic conveyor can be applied to transmit and sort various objects such as blood/cancer cells and microorganisms.
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http://dx.doi.org/10.1039/d0lc00787kDOI Listing
October 2020

Low serum trypsinogen levels in chronic pancreatitis: Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis.

Pancreatology 2020 Oct 5;20(7):1368-1378. Epub 2020 Sep 5.

Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Cell Biology and Molecular Physiology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Background: Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function.

Aim: To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP.

Methods: Serum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features.

Results: A final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures).

Conclusions: Very low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.
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http://dx.doi.org/10.1016/j.pan.2020.08.025DOI Listing
October 2020

Application of Spatio-Temporal Context and Convolution Neural Network (CNN) in Grooming Behavior of (Diptera: Trypetidae) Detection and Statistics.

Insects 2020 Aug 24;11(9). Epub 2020 Aug 24.

School of Computer Science, Yangtze University, Jingzhou 434023, China.

Statistical analysis and research on insect grooming behavior can find more effective methods for pest control. Traditional manual insect grooming behavior statistical methods are time-consuming, labor-intensive, and error-prone. Based on computer vision technology, this paper uses spatio-temporal context to extract video features, uses self-built Convolution Neural Network (CNN) to train the detection model, and proposes a simple and effective grooming behavior detection method, which automatically detects the grooming behaviors of the flies and analysis results by a computer program. Applying the method training detection model proposed in this paper, the videos of 22 adult flies with a total of 1320 min of grooming behavior were detected and analyzed, and the total detection accuracy was over 95%, the standard error of the accuracy of the behavior detection of each adult flies was less than 3%, and the difference was less than 15% when compared with the results of manual observation. The experimental results show that the method in this paper greatly reduces the time of manual observation and at the same time ensures the accuracy of insect behavior detection and analysis, which proposes a new informatization analysis method for the behavior statistics of and also provides a new idea for related insect behavior identification research.
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http://dx.doi.org/10.3390/insects11090565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564701PMC
August 2020

Uncertain Water Environment Carrying Capacity Simulation Based on the Monte Carlo Method-System Dynamics Model: A Case Study of Fushun City.

Int J Environ Res Public Health 2020 08 13;17(16). Epub 2020 Aug 13.

School of New Energy and Environment, Jilin University, Changchun 130021, China.

Water environment carrying capacity (WECC) is an effective indicator that can help resolve the contradiction between social and economic development and water environment pollution. Considering the complexity of the water environment and socioeconomic systems in Northeast China, this study establishes an evaluation index system and a system dynamics (SD) model of WECC in Fushun City, Liaoning, China, through the combination of the fuzzy analytic hierarchy process and SD. In consideration of the uncertainty of the future development of society, the Monte Carlo and scenario analysis methods are used to simulate the WECC of Fushun City. Results show that if the current social development mode is maintained, then the WECC in Fushun will have a slow improvement in the future, and a "general" carrying state with a WECC index of 0.566 in 2025 will be developed. Moreover, focusing on economic development (Scheme 1 with a WECC index of [0.22, 0.45] in 2025) or environmental protection (Scheme 2 with a WECC index of [0.48, 0.68] in 2025) cannot effectively improve the local water environment. Only by combining the two coordinated development modes (Scheme 3) can WECC be significantly improved and achieve "general" or "good" carrying state with a WECC index of [0.59, 0.79]. An important development of this study is that the probability of each scheme's realization can be calculated after different schemes are formulated. In turn, the feasibility of the scheme will be evaluated after knowing the probability, so as to determine the path suitable for local development. This is of great significance for future urban planning.
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http://dx.doi.org/10.3390/ijerph17165860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460045PMC
August 2020

Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Cell 2020 09 18;182(5):1328-1340.e13. Epub 2020 Aug 18.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, P.R. China.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.
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http://dx.doi.org/10.1016/j.cell.2020.07.023DOI Listing
September 2020

Circular RNA ZNF609 Promoted Hepatocellular Carcinoma Progression by Upregulating PAP2C Expression via Sponging miR-342-3p.

Onco Targets Ther 2020 4;13:7773-7783. Epub 2020 Aug 4.

Department of Traditional Chinese Medicine, Guizhou Provincial People's Hospital, Guiyang, People's Republic of China.

Background: Emerging evidence has revealed that circular RNAs (circRNAs) participated in hepatocellular carcinoma (HCC) development. However, the roles of most circRNAs have not been studied.

Methods: CircZNF609, miR-342-3p and RAP2C expressions were assessed by qPCR or Western blot. Loss-of-function experiments were performed using si-circZNF609 transfection, followed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Informatic tools and rescue experiments were carried out to investigate the underlying mechanisms.

Results: We showed that circZNF609 was overexpressed in HCC tissues and cells, as well as associated with poor clinical characteristics. Depletion of circZNF609 restrained HCC cell viability, migration and invasion while enhanced cell apoptosis. As to mechanism, miR-342-3p was sponged by circZNF609, and RAP2C was targeted by miR-342-3p. The effects on HCC cells induced by si-circZNF609 could be reversed by miR-342-3p inhibitor or RAP2C. In vivo, circZNF609 knockdown inhibited tumorigenesis of HCC mice, confirming the findings in vitro.

Conclusion: CircZNF609 was highly expressed in HCC tissues and driven HCC progression by sponging miR-342-3p and upregulating RAP2C. This study may provide new potential therapeutic targets for HCC treatment.
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http://dx.doi.org/10.2147/OTT.S253936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414977PMC
August 2020

Transcriptome analysis of the Larimichthys polyactis under heat and cold stress.

Cryobiology 2020 10 8;96:175-183. Epub 2020 Aug 8.

Institute of Hydrobiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.

The small yellow croaker (Larimichthys polyactis) is an economically important marine fish that is widely distributed in the East Sea, Yellow Sea and Bohai of China. However, the wild populations of L. polyactis are severely depleted, and there is currently a developing large-scale artificial propagation of this fish for aquaculture. However, the current variety of L. polyactis that is cultivated is not capable to coping with large fluctuations in temperature. Therefore, it is important to understand the molecular mechanisms that are activated in response to temperature stress in the L. polyactis. Here, we conducted transcriptomic analysis of the liver of L. polyactis under heat and cold stress. A total of 270,844,888, 265,727,006 and 259,666,218 clean reads were generated from high temperature group, low temperature group and control group, respectively, and comparing expression of genes in these transcriptomes, 10,878 unigenes that were differential expressed were identified. Seventeen of the differentially expressed unigenes were validated by qRT-PCR. Pathway enrichment analysis identified that the ER pathway, immune signaling pathway and metabolic response pathway were affected by temperature stress. The results of this study provide a comprehensive overview of temperature stress-induced transcriptional patterns in liver tissues of the L. polyactis. In addition, these results can guide future molecular studies of heat and cold stress response in this species for improving the stock used for aquaculture.
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http://dx.doi.org/10.1016/j.cryobiol.2020.06.014DOI Listing
October 2020

A first genetic linage map construction and QTL mapping for growth traits in Larimichthys polyactis.

Sci Rep 2020 07 15;10(1):11621. Epub 2020 Jul 15.

Xiangshan Gangwan Aquatic Seeds Co., Ltd, Ningbo, 315700, China.

Larimichthys polyactis is a commercially important marine fish species in Eastern Asia, yet very few genetic resources exist. In particular, genetic linkage maps are critical tools for genetic breeding. In this study, we generated a high resolution linkage map from a family of 110 individuals and their parents by resequencing the individuals. 3,802 effective SNPs were mapped to 24 linkage groups (LGs). The map spanned 2,567.39 cm, with an average marker interval of 0.66 cm. We used the map to conduct QTL analysis for growth traits, and found 31 markers were significantly associated with growth-related traits. Specifically, three SNPs were identified for total length, nineteen SNPs for body length, and nine SNPs for body weight. The identified SNPs could explain 15.2-22.6% of the phenotypic variation. SNPs associated with growth traits were distributed on LG6 and LG11, and candidate genes included, kif26b, bat1, gna1, gbgt1, and amfr, which may regulate growth. The linkage map and mapped QTLs would be useful for improving the quality of L. polyactis via marker-assisted selection.
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http://dx.doi.org/10.1038/s41598-020-68592-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363912PMC
July 2020

Mechanisms and Models of Adsorption: TiO-Supported Biochar for Removal of 3,4-Dimethylaniline.

ACS Omega 2020 Jun 1;5(23):13630-13640. Epub 2020 Jun 1.

School of Civil Engineering and Architecture, Wuhan University of Technology, Wuhan 430070, China.

Here, 3,4-dimethylaniline (3,4-DMA) was selected as a representative organic substance of aniline compounds. A biochar-titanium dioxide (BC-TiO) composite was prepared by the sol-gel method to investigate its adsorption ability toward the 3,4-DMA compound. Simultaneously, the prepared composite's adsorption ability and physical and physicochemical properties were also investigated. The isotherm studies confirmed that the adsorption of 3,4-DMA on both BC and BC-TiO composite agrees with the Langmuir and Toth adsorption models, which means the formation of a monolayer of 3,4-DMA on the surface. The maximum adsorption capacity of 3,4-DMA was 322.58 mg g and 285.71mg g for BC and BC-TiO, respectively. Furthermore, the adsorption kinetics reveals that the adsorption process of 3,4-DMA on BC and the BC-TiO composite is controlled by the pseudo-second-order kinetic model with an of 0.99.
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http://dx.doi.org/10.1021/acsomega.0c00619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301375PMC
June 2020

MELK Accelerates the Progression of Colorectal Cancer via Activating the FAK/Src Pathway.

Biochem Genet 2020 Oct 29;58(5):771-782. Epub 2020 May 29.

Department of Imaging, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Road, Guiyang, 550004, Guizhou, China.

Maternal embryo leucine zipper kinase (MELK) has a higher expression level in a variety of cancers and involved in progression of colorectal cancer. The MELK expression levels in colorectal cancer tissues and cells were detected by RT-qPCR. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and transwell assays were used to examine the effect of the MELK konckdown on the proliferation, migration and invasion of colorectal cancer cells. Western blot analysis was used to detect the protein level of MELK and the downstream signaling pathways related proteins. Our findings indicated that MELK expression in colorectal cancer tissues was significantly higher than that in para-carcinoma tissues. Knockdown of MELK with shRNA had strong inhibition effects on the proliferation, migration and invasion of colorectal cancer cells. MELK knockdown could also decrease the phosphorylation level of AKT through FAK/Src pathway. Our results indicated downregulation of MELK retarded the progression of CRC by inhibition of the phosphorylation level of AKT through inactivating FAK/Src pathways. Therefore, MELK has the potential to be explored as a new therapeutic target and knockdown can be used as a potential treatment strategy for colorectal cancer.
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http://dx.doi.org/10.1007/s10528-020-09974-xDOI Listing
October 2020

USP38 regulates the stemness and chemoresistance of human colorectal cancer via regulation of HDAC3.

Oncogenesis 2020 May 13;9(5):48. Epub 2020 May 13.

Department of Traditional Chinese Medicine, Guizhou Provincial People's Hospital, 550002, Guiyang, Guizhou, China.

Histone modification represents a crucial level of gene expression regulation and is actively involved in the carcinogenesis of human colorectal cancer. Histone acetyltransferases and deacetylases modulate the landscape of histone acetylation, which controls key genes of colorectal cancer pathology. However, the fine tune of histone deacetylases, especially the modification of histone deacetylases that facilitate colorectal cancer, remains elusive. Here, we identified that an ubiquitin-specific protease (USP), USP38, was downregulated in clinical colorectal cancer samples and colorectal cancer cell lines. Importantly, our results showed that USP38 was a specific deubiquitinase of histone deacetylase 3 (HDAC3), which cleaved the lysine 63 ubiquitin chain. Ubiquitination of HDAC3 resulted in a decreased level of histone acetylation and finally led to upregulation of cancer stem cell-related genes. In addition, our results demonstrated a tumor suppressor role of USP38 in colorectal cancer via inhibiting cancer stem cell populations. Most importantly, the ubiquitination level of HDAC3 was responsible for USP38 mediated regulation of cancer stem cell-related transcripts. Our data provided functional insights of USP38 and HDAC3 in colorectal cancer and revealed novel mechanisms of ubiquitination mediated epigenetic regulation.
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http://dx.doi.org/10.1038/s41389-020-0234-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220910PMC
May 2020

[email protected]: Non-Isolated-Pentagon-Rule Cages Prevail with the UO Configuration Determined by Cage Shape and Dominated by Multicenter Bonds.

Inorg Chem 2020 May 28;59(10):7039-7048. Epub 2020 Apr 28.

School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China.

Endohedral clusterfullerenes (ECFs) are fullerene cages with various metallic clusters trapped inside. So far, the actinide-based ECFs are rather scarce with their possible structures and chemistry remaining largely unexplored. Herein, density functional theory calculations characterized that the recently synthesized [email protected] could be [email protected](17 490)-C or [email protected](19 138)-C, whose cages have two or one pentagon adjacencies (PAs) and thus both violate the isolated pentagon rule (IPR). It is noteworthy that they are the first actinide-based ECFs bearing non-IPR outer cages. They are also the first (17 490)- and (19 138)-C-based oxide ECFs. Moreover, [email protected](19 138)-C is the first example of a hexavalent metal cluster within the (19 138)-C cage. Interestingly, although trapped by the two same-sized cages, the UO unit exhibits a bent and a perfect linear configuration, respectively, indicative of the crucial role of cage shape in steering the internal cluster configuration. Their electronic structures can be formally described as (UO)@C with primary electrostatic attractions and secondary covalent interactions between cluster and cage. Significantly, bonding analyses reveal that the encaged UO moiety may only features two three-center, two-electron (3c-2e) U-O-U bonds with completely absent common two-center bonds.
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http://dx.doi.org/10.1021/acs.inorgchem.0c00518DOI Listing
May 2020

Endoscopic ultrasound-guided gallbladder fistulization for cholecystolithotomy after endoscopic transpapillary cannulation of the gallbladder in patients with gallstones and common bile duct stones.

J Dig Dis 2020 Jul 17;21(7):422-425. Epub 2020 Jun 17.

Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.

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http://dx.doi.org/10.1111/1751-2980.12865DOI Listing
July 2020

Undiscovered Effect of C↔N Interchange Inside the Metal Carbonitride Clusterfullerenes: A Density Functional Theory Investigation.

Inorg Chem 2020 May 16;59(9):6518-6527. Epub 2020 Apr 16.

School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China.

Putting different metal clusters into the fullerene cages form the so-called "endohedral clusterfullerenes" (ECFs), among which all the carbonitride ECFs feature a common NC unit coordinating with either one or three metal atoms. Unfortunately, their internal N and C atoms are difficult to be distinguished experimentally, resulting in the fact that the exact structure and bonding nature of the encased metal cluster still remain unclear thus far. In this work, density functional theory calculations were performed for several representative carbonitride ECFs: [email protected] (M = Y, Tb; 2 = 76, 82) and [email protected] (2 = 78, 80). For the first time, we focused on the C ↔ N interchange inside the cages and its effect on the chemical bonding of the trapped clusters. Computational results reveal that the two types of ECFs energetically favor the N and C atoms at the cluster center, respectively. The preference can be interpreted by the difference in several aspects, such as the energy of isolated clusters, charge states of (CN), and cluster-cage interactions, as well as hyperconjugation of the internal clusters. The detailed wave function analyses indicate that [email protected] and [email protected] bear a C≡N triple bond and a C═N double bond, respectively, regardless of the NC orientation. Compared with its slightly influence on the bonding patterns of the encaged MNC clusters, the C ↔ N interchange dramatically affects that of the ScCN units involving two-center two-electron (2c-2e) bonds, undiscovered three-center two-electron (3c-2e), and four-center two-electron (4c-2e) bonds.
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http://dx.doi.org/10.1021/acs.inorgchem.0c00610DOI Listing
May 2020

Using Electrolytic Manganese Residue to prepare novel nanocomposite catalysts for efficient degradation of Azo Dyes in Fenton-like processes.

Chemosphere 2020 Aug 17;252:126487. Epub 2020 Mar 17.

Key Laboratory of Catalysis Conversion and Energy Materials Chemistry, Ministry of Education, PR China; Engineering Research Center for Heavy Metal Pollution Control of Hubei Province, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan, 430074, PR China. Electronic address:

In this study, Electrolytic Manganese Residue (EMR) was treated by EDTA-2Na/NaOH, ultrasonic etching, and hydrothermal reaction to obtain a novel nanocomposite catalyst (called N-EMR), which then was used, together with HO, to treat synthetic textile wastewater containing Reactive Red X-3B, Methyl Orange, Methylene blue and Acid Orange 7. Results indicated that the N-EMR had a nano-sheet structure in sizes of 100-200 nm; new iron and manganese oxides with high activity were produced. The mixture of a small amount of N-EMR (40 mg/L) and HO (0.4 × 10 M) could removal about 99% of azo dyes (at 100 mg/L in 100 mL) within 6-15 min, much faster than many advanced oxidation processes (AOPs) reported in the literature. The elucidation of the associated mechanism for azo dyes degradation indicates that azo dyes were attacked by superoxide radicals, hydroxyl radicals, and electron holes generated within system. N-EMR was found to be reusable and showed limited inhibition by co-existing anions and cations. Moreover, high removal efficiency of azo dyes could happen in the system with a wide range of pH (1-8.5) and temperatures (25-45 °C), indicating that the process developed in this study may have broad application potential in treatment of azo dyes contaminated wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126487DOI Listing
August 2020