59,700 results match your criteria toxin binding

Cys183 and Cys258 in Cry49Aa toxin from Lysinibacillus sphaericus are essential for toxicity to Culex quinquefasciatus larvae.

Arch Microbiol 2021 Jun 23. Epub 2021 Jun 23.

College of Life Sciences, Gannan Normal University, Shida South Road 1, Ganzhou City, Jiangxi Province, 341000, People's Republic of China.

The two-component Cry48Aa/Cry49Aa toxin produced by Lysinibacillus sphaericus shows specifically toxic to Culex quinquefasciatus mosquito larvae. Cry49Aa C-terminal domain is responsible for specific binding to the larval gut cell membrane, while its N-terminal domain is required for interaction with Cry48Aa. To investigate functional role of cysteine in Cry49Aa, four cysteine residues at positions 70, 91, 183, and 258 were substituted by alanine. Read More

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Anthrax toxin translocation complex reveals insight into the lethal factor unfolding and refolding mechanism.

Sci Rep 2021 Jun 22;11(1):13038. Epub 2021 Jun 22.

Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.

Translocation is essential to the anthrax toxin mechanism. Protective antigen (PA), the binding component of this AB toxin, forms an oligomeric pore that translocates lethal factor (LF) or edema factor, the active components of the toxin, into the cell. Structural details of the translocation process have remained elusive despite their biological importance. Read More

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Structure of AMH bound to AMHR2 provides insight into a unique signaling pair in the TGF-β family.

Proc Natl Acad Sci U S A 2021 Jun;118(26)

Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH 45267;

Anti-Müllerian hormone (AMH), or Müllerian-inhibiting substance, is a protein hormone that promotes Müllerian duct regression during male fetal sexual differentiation and regulation of folliculogenesis in women. AMH is a member of the transforming growth factor beta (TGF-β) family, which has evolved to signal through its own dedicated type II receptor, AMH receptor type II (AMHR2). Structures of other TGF-β family members have revealed how ligands infer specificity for their cognate receptors; however, it is unknown how AMH binds AMHR2 at the molecular level. Read More

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Which Is Stronger? A Continuing Battle Between Cry Toxins and Insects.

Front Microbiol 2021 1;12:665101. Epub 2021 Jun 1.

State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.

In this article, we review the latest works on the insecticidal mechanisms of Cry toxins and the resistance mechanisms of insects against Cry toxins. Currently, there are two models of insecticidal mechanisms for Cry toxins, namely, the sequential binding model and the signaling pathway model. In the sequential binding model, Cry toxins are activated to bind to their cognate receptors in the mid-intestinal epithelial cell membrane, such as the glycophosphatidylinositol (GPI)-anchored aminopeptidases-N (APNs), alkaline phosphatases (ALPs), cadherins, and ABC transporters, to form pores that elicit cell lysis, while in the signaling pathway model, the activated Cry toxins first bind to the cadherin receptor, triggering an extensive cell signaling cascade to induce cell apoptosis. Read More

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[Research progress of TLR4 signaling pathway and its targeted drugs].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jul;37(7):657-662

School of Life Science, Liaoning Normal University, Dalian 116081, China. *Corresponding author, E-mail:

The innate immune system uses pattern recognition receptors (PRRs) or other molecular receptors to recognize pathogenic microorganisms such as the invading bacteria, and prevents the spread of infection by triggering an inflammatory response, which plays a vital role in antimicrobial defense. Toll-like receptor-4 (TLR4) is the core of innate immune system in mammals and plays a key role in bacterial endotoxin-mediated inflammation. TLR4 recognizes lipopolysaccharide (LPS) on the cell wall of Gram-negative bacteria, thereby activating the TLR4 signaling pathway, releasing pro-inflammatory factors and chemokines, and inducing inflammation. Read More

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Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA.

Nucleic Acids Res 2021 Jun 17. Epub 2021 Jun 17.

Structural Biology Brussels, Department of Biotechnology, Vrije Universiteit Brussel, B-1050 Brussel, Belgium.

The rnlAB toxin-antitoxin operon from Escherichia coli functions as an anti-phage defense system. RnlA was identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the toxin RnlA requires tight regulation by the antitoxin RnlB, the mechanism of which remains unknown. Read More

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Glycolipid-Anchored Proteins on Bioengineered Extracellular Vesicles for Lipopolysaccharide Neutralization.

ACS Appl Mater Interfaces 2021 Jun 17. Epub 2021 Jun 17.

Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea.

Extracellular vesicles (EVs) with native membrane proteins possess a variety of functions. EVs have become increasingly important platforms for incorporating a new peptide/protein with additional functions on their membranes using genetic manipulation of producer cells. Although directly harnessing native membrane proteins on EVs for functional studies is promising, limited studies have been conducted to confirm its potential. Read More

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Designing of Potential Polyvalent Vaccine Model for Respiratory Syncytial Virus by System Level Immunoinformatics Approaches.

Biomed Res Int 2021 28;2021:9940010. Epub 2021 May 28.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, China.

Background: Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment.

Methods: In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Read More

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Ceramide structure dictates glycosphingolipid nanodomain assembly and function.

Nat Commun 2021 06 16;12(1):3675. Epub 2021 Jun 16.

Institut Curie, PSL Research University, U1143 INSERM, UMR3666 CNRS, Cellular and Chemical Biology unit, Paris, Cedex, France.

Gangliosides in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. How gangliosides are dynamically organized and how they respond to ligand binding is poorly understood. Using fluorescence anisotropy imaging of synthetic, fluorescently labeled GM1 gangliosides incorporated into the plasma membrane of living cells, we found that GM1 with a fully saturated C16:0 acyl chain, but not with unsaturated C16:1 acyl chain, is actively clustered into nanodomains, which depends on membrane cholesterol, phosphatidylserine and actin. Read More

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Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials.

ACS Appl Mater Interfaces 2021 Jun 15. Epub 2021 Jun 15.

Laboratory for Environmental and Life Sciences, University of Nova Gorica Nova Gorica 5000, Slovenia.

Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (∼2.5 × ∼ 4 nm) and limited valence for interactions might pose restrictions for applications, especially regarding their modest capacity for multivalent and cooperative interaction. In this work, modular protein constructs have been designed, in which nanobodies are fused to protein domains to provide further functionalities and to favor oligomerization into stable self-assembled nanoparticles. Read More

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The Ability of Probiotic Lactobacillus Strains in Removal of Benzo[a]pyrene: a Response Surface Methodology Study.

Probiotics Antimicrob Proteins 2021 Jun 15. Epub 2021 Jun 15.

Department of Food Science and Technology, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

In this study, the ability of various lactic acid bacteria was assessed in removing benzo[a]pyrene (BaP) from contaminated phosphate buffer saline (PBS). Response surface methodology (RSM) was performed using Box-Behnken design to investigate the effect of four independent variables including pH (5-7), incubation time (1-24 h), cell density (10-10 cfu/mL), and initial BaP concentration (5-15 mg/kg) at three levels to evaluate in vitro removal of BaP as response. The results showed that all the tested strains were able to remove BaP from PBS and this reduction was entirely strain-specific. Read More

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Gene Conversion Facilitates the Adaptive Evolution of Self-Resistance in Highly Toxic Newts.

Mol Biol Evol 2021 Jun 15. Epub 2021 Jun 15.

Department of Biological Sciences, Virginia Tech, Blacksburg, United States.

Reconstructing the histories of complex adaptations and identifying the evolutionary mechanisms underlying their origins are two of the primary goals of evolutionary biology. Taricha newts, which contain high concentrations of the deadly toxin tetrodotoxin (TTX) as an antipredator defense, have evolved resistance to self-intoxication, which is a complex adaptation requiring changes in six paralogs of the voltage-gated sodium channel (Nav) gene family, the physiological target of TTX. Here, we reconstruct the origins of TTX self-resistance by sequencing the entire Nav gene family in newts and related salamanders. Read More

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Chemical Space Exploration of DprE1 Inhibitors Using Chemoinformatics and Artificial Intelligence.

ACS Omega 2021 Jun 25;6(22):14430-14441. Epub 2021 May 25.

CSIR-Institute of Microbial Technology, Chandigarh 160036, India.

Tuberculosis (TB), entrained by , continues to be an enfeebling disease, killing nearly 1.5 million people in 2019, with 2 billion people worldwide affected by latent TB. The multidrug-resistant and totally drug-resistant emerging strains further exacerbate the TB infection. Read More

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Exogenous Gene Expression and Insect Resistance in Dual Bt Toxin × 'Neva' Transgenic Plants.

Front Plant Sci 2021 28;12:660226. Epub 2021 May 28.

Forest Department, Forestry College, Hebei Agricultural University, Baoding, China.

(Bt) insecticidal protein genes are important tools in efforts to develop insect resistance in poplar. In this study, the and Bt toxin genes were simultaneously transformed into the poplar variety × 'Neva' by -mediated transformation to explore the exogenous gene expression and insect resistance, and to examine the effects of Bt toxin on the growth and development of larvae after feeding on the transgenic plant. Integration and expression of the transgenes were determined by molecular analyses and the insect resistance of transgenic lines was evaluated in feeding experiments. Read More

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Tethered peptide toxins for ion channels.

Methods Enzymol 2021 1;654:203-224. Epub 2021 Apr 1.

Departments of Pediatrics, Physiology & Biophysics, and Pharmaceutical Sciences, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, CA, United States. Electronic address:

In this method paper, we describe protocols for using membrane-tethered peptide toxins (T-toxins) to study the structure/function and biophysics of toxin-channel interactions with two-electrode voltage clamp (TEVC). Here, we show how T-toxins can be used to determine toxin equilibrium affinity, to quantify toxin surface level by enzyme-linked immunosorbent assay (ELISA) and/or single-molecule total internal reflection fluorescence (smTIRF) microscopy, to assess toxin association and dissociations rate, to identify toxin residues critical to binding via scanning mutagenesis, and to study of toxin blocking mechanism. The sea anemone type I (SAK1) toxin HmK and a potassium channel are used to demonstrate the strategies. Read More

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Mechanisms of typhoid toxin neutralization by antibodies targeting glycan receptor binding and nuclease subunits.

iScience 2021 May 20;24(5):102454. Epub 2021 Apr 20.

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

Nearly all clinical isolates of Typhi, the cause of typhoid fever, are antibiotic resistant. All Typhi isolates secrete an AB exotoxin called typhoid toxin to benefit the pathogen during infection. Here, we demonstrate that antibiotic-resistant Typhi secretes typhoid toxin continuously during infection regardless of antibiotic treatment. Read More

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LD-transpeptidases: the great unknown among the peptidoglycan cross-linkers.

FEBS J 2021 Jun 10. Epub 2021 Jun 10.

Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden, Umeå Centre for Microbial Research, Umeå University, Sweden.

The peptidoglycan (PG) cell wall is an essential polymer for the shape and viability of bacteria. Its protective role is in great part provided by its mesh-like character. Therefore, PG-cross-linking enzymes like the penicillin-binding proteins (PBPs) are among the best targets for antibiotics. Read More

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Role of TRPM2 in brain tumours and potential as a drug target.

Acta Pharmacol Sin 2021 Jun 9. Epub 2021 Jun 9.

Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Ion channels are ubiquitously expressed in almost all living cells, and are the third-largest category of drug targets, following enzymes and receptors. The transient receptor potential melastatin (TRPM) subfamily of ion channels are important to cell function and survival. Studies have shown upregulation of the TRPM family of ion channels in various brain tumours. Read More

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Therapeutic Potential of Novel Mastoparan-Chitosan Nanoconstructs Against Clinical MDR : In silico, in vitro and in vivo Studies.

Int J Nanomedicine 2021 1;16:3755-3773. Epub 2021 Jun 1.

Department of Microbiology, Armed Forces Institute of Pathology, National University of Medical Sciences, Rawalpindi, Pakistan.

Purpose: antibiotic resistant infections in high-risk patients are a great challenge for researchers and clinicians worldwide. In an effort to achieve potent bactericidal outcomes, a novel chitosan-mastoparan nanoconstruct (Mast-Cs NC) was designed and assessed for its therapeutic potential through in silico, in vitro and in vivo experimentation against clinical multidrug-resistant (MDR) .

Methods: Optimized 3D structures of mastoparan and chitosan were coupled computationally through an ionic cross-linker to generate a circular ring of chitosan encasing mastoparan. Read More

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Potential genes associated with survival of Acinetobacter baumannii under ciprofloxacin stress.

Microbes Infect 2021 Jun 4:104844. Epub 2021 Jun 4.

Department of Biotechnology, Panjab University, BMS Block-I, Sector-25, Chandigarh, India, 160014. Electronic address:

Acinetobacter baumannii is an opportunistic pathogen that has acquired resistance to all available drugs. The rise in multi-drug resistance in A. baumannii has been exacerbated by its ability to tolerate antibiotics due to the persister cells, which are phenotypic variants of normal cells that can survive various stress conditions, resulting in chronicity of infection. Read More

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Essential functions of chaperones and adaptors of protein secretion systems in Gram-negative bacteria.

FEBS J 2021 Jun 6. Epub 2021 Jun 6.

Department of Ecosystem and Public Health, University of Calgary, Canada.

Equipped with a plethora of secreted toxic effectors, protein secretion systems are essential for bacteria to interact with and manipulate their neighboring environment to survive in host microbiota and other highly competitive communities. While effectors have received spotlight attention in secretion system studies, many require accessory chaperone and adaptor proteins for proper folding/unfolding and stability throughout the secretion process. Here, we review the functions of chaperones and adaptors of three protein secretions systems, type 3 secretion system (T3SS), type 4 secretion system (T4SS), and type 6 secretion system (T6SS), which are employed by many Gram-negative bacterial pathogens to deliver toxins to bacterial, plant, and mammalian host cells through direct contact. Read More

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Structural Analysis of Toxin-Neutralizing, Single-Domain Antibodies that Bridge Ricin's A-B Subunit Interface.

J Mol Biol 2021 Jun 3;433(15):167086. Epub 2021 Jun 3.

Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA. Electronic address:

Ricin toxin kills mammalian cells with notorious efficiency. The toxin's B subunit (RTB) is a Gal/GalNAc-specific lectin that attaches to cell surfaces and promotes retrograde transport of ricin's A subunit (RTA) to the trans Golgi network (TGN) and endoplasmic reticulum (ER). RTA is liberated from RTB in the ER and translocated into the cell cytoplasm, where it functions as a ribosome-inactivating protein. Read More

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Mycoplasma pneumoniae CARDS toxin exploits host cell endosomal acidic pH and vacuolar ATPase proton pump to execute its biological activities.

Sci Rep 2021 Jun 2;11(1):11571. Epub 2021 Jun 2.

Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.

Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia among hospitalized children in the United States. It is also responsible for a spectrum of other respiratory tract disorders and extrapulmonary manifestations in children and adults. The main virulence factor of M. Read More

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Large Clostridial Toxins: Mechanisms and Roles in Disease.

Microbiol Mol Biol Rev 2021 Jun 2:e0006421. Epub 2021 Jun 2.

Molecular Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.

Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family include Clostridioides difficile toxins TcdA and TcdB, Paeniclostridium sordellii toxins TcsL and TcsH, Clostridium novyi toxin TcnA, and Clostridium perfringens toxin TpeL. Since the 19th century, LCT-secreting bacteria have been isolated from the blood, organs, and wounds of diseased individuals, and LCTs have been implicated as the primary virulence factors in a variety of infections, including C. Read More

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Therapeutic Uses of Bacterial Subunit Toxins.

Toxins (Basel) 2021 05 26;13(6). Epub 2021 May 26.

Division of Molecular Medicine, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.

The B subunit pentamer verotoxin (VT aka Shiga toxin-Stx) binding to its cellular glycosphingolipid (GSL) receptor, globotriaosyl ceramide (Gb) mediates internalization and the subsequent receptor mediated retrograde intracellular traffic of the AB5 subunit holotoxin to the endoplasmic reticulum. Subunit separation and cytosolic A subunit transit via the ER retrotranslocon as a misfolded protein mimic, then inhibits protein synthesis to kill cells, which can cause hemolytic uremic syndrome clinically. This represents one of the most studied systems of prokaryotic hijacking of eukaryotic biology. Read More

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Alleviation of LPS-Induced Inflammation and Septic Shock by K8 Lysates.

Int J Mol Sci 2021 May 31;22(11). Epub 2021 May 31.

Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, Korea.

We previously showed that K8 and its cell wall components have immunoregulatory effects. In this study, we demonstrate that pre-treatment of K8 lysates reduced LPS-induced TNF-α production in THP-1 cells by down-regulating the early signals of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The down-regulation of signals may be caused by the induction of negative regulators involved in toll-like receptor (TLR)-mediated signaling. Read More

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Anti-Inflammatory Effect of Auranofin on Palmitic Acid and LPS-Induced Inflammatory Response by Modulating TLR4 and NOX4-Mediated NF-κB Signaling Pathway in RAW264.7 Macrophages.

Int J Mol Sci 2021 May 31;22(11). Epub 2021 May 31.

Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea.

Chronic inflammation, which is promoted by the production and secretion of inflammatory mediators and cytokines in activated macrophages, is responsible for the development of many diseases. Auranofin is a Food and Drug Administration-approved gold-based compound for the treatment of rheumatoid arthritis, and evidence suggests that auranofin could be a potential therapeutic agent for inflammation. In this study, to demonstrate the inhibitory effect of auranofin on chronic inflammation, a saturated fatty acid, palmitic acid (PA), and a low concentration of lipopolysaccharide (LPS) were used to activate RAW264. Read More

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Characterization and Pharmacological Inhibition of the Pore-Forming CDTb Toxin.

Toxins (Basel) 2021 05 28;13(6). Epub 2021 May 28.

Institute of Pharmacology and Toxicology, Ulm University Medical Center, 89081 Ulm, Germany.

The clinically highly relevant releases several AB-type toxins that cause diseases such as diarrhea and pseudomembranous colitis. In addition to the main virulence factors Rho/Ras-glycosylating toxins TcdA and TcdB, hypervirulent strains produce the binary AB-type toxin CDT. CDT consists of two separate proteins. Read More

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Cell Biological Responses after Shiga Toxin-1 Exposure to Primary Human Glomerular Microvascular Endothelial Cells from Pediatric and Adult Origin.

Int J Mol Sci 2021 May 25;22(11). Epub 2021 May 25.

Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands.

Hemolytic uremic syndrome (HUS) is characterized by a triad of symptoms consisting of hemolytic anemia, thrombocytopenia and acute renal failure. The most common form of HUS is caused by an infection with Shiga toxin (Stx) producing bacteria (STEC-HUS), and the kidneys are the major organs affected. The development of HUS after an infection with Stx occurs most frequently in children under the age of 5 years. Read More

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Liposomes Prevent In Vitro Hemolysis Induced by Streptolysin O and Lysenin.

Membranes (Basel) 2021 May 18;11(5). Epub 2021 May 18.

Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA.

The need for alternatives to antibiotics in the fight against infectious diseases has inspired scientists to focus on antivirulence factors instead of the microorganisms themselves. In this respect, prior work indicates that tiny, enclosed bilayer lipid membranes (liposomes) have the potential to compete with cellular targets for toxin binding, hence preventing their biological attack and aiding with their clearance. The effectiveness of liposomes as decoy targets depends on their availability in the host and how rapidly they are cleared from the circulation. Read More

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