Publications by authors named "Bin Tian"

344 Publications

DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein.

Front Microbiol 2021 12;12:700434. Epub 2021 Nov 12.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-β by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-β-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity.
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http://dx.doi.org/10.3389/fmicb.2021.700434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633874PMC
November 2021

Development of an indirect ELISA method based on the VP4 protein for detection antibody against duck hepatitis A virus type 1.

J Virol Methods 2021 Nov 30;300:114393. Epub 2021 Nov 30.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, 611130, PR China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, 611130, PR China.

In Picornavirus, the VP4 gene is located inside the viral capsid, but the antibodies it produces have neutralizing activity. At the same time, we know that the VP4 gene is relatively conserved among the four structural proteins, which makes the usage VP4 protein-based antigen potentially meaningful. Therefore, we used purified duck hepatitis A virus type 1 (DHVA-1) recombinant VP4 protein as the coating antigen to establish an indirect method. The optimal antigen, serum and enzyme-labeled antibody dilutions were 1:400 (3.375 μg/mL), 1:80 and 1:1600, respectively. The optimal blocking buffer was 1% skimmed milk powder. The cutoff value was determined to be 0.203, and the analytical sensitivity was 1:1600. The established ELISA method has good specificity, repeatability and sensitivity. It has a high coincidence rate of 70.8 % with the DHVA-1 as the coating antigen. So, it can be used for the detection of DHAV-1 serum antibodies.
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http://dx.doi.org/10.1016/j.jviromet.2021.114393DOI Listing
November 2021

Recent advances in printed flexible heaters for portable and wearable thermal management.

Mater Horiz 2021 Jun 19;8(6):1634-1656. Epub 2021 Feb 19.

Laboratory of Printable Functional Materials and Printed Electronics, School of Printing and Packaging, Wuhan University, Wuhan 430072, P. R. China.

Flexible resistive heaters (FRHs) with high heating performance, large-area thermal homogeneity, and excellent thermal stability are very desirable in modern life, owing to their tremendous potential for portable and wearable thermal management applications, such as body thermotherapy, on-demand drug delivery, and artificial intelligence. Printed electronic (PE) technologies, as emerging methods combining conventional printing techniques with solution-processable functional ink have been proposed to be promising strategies for the cost-effective, large-scale, and high-throughput fabrication of printed FRHs. This review summarizes recent progress in the main components of FRHs, including conductive materials and flexible or stretchable substrates, focusing on the formulation of conductive ink systems for making printed FRHs by a variety of PE technologies including screen printing, inkjet printing, roll-to-roll (R2R) printing and three-dimensional (3D) printing. Various challenges facing the commercialization of printed FRHs and improved methods for portable and wearable thermal management applications have been discussed in detail to overcome these problems.
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http://dx.doi.org/10.1039/d0mh01950jDOI Listing
June 2021

(Fabaceae), a new species from Guangdong, China, based on molecular and morphological data.

PhytoKeys 2021 15;185:43-53. Epub 2021 Nov 15.

State Key Laboratory of Biocontrol and Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China Sun Yat-sen University Guangzhou China.

(Fabaceae), a new species from Danxiashan National Nature Reserve in Guangdong Province, is described and illustrated. The new species is morphologically similar to , but it can be easily distinguished by its thin leathery leaflets and long peduncles. Phylogenetic analysis based on ITS confirmed that the new species belongs to Lespedezasubg.Macrolespedeza. The new species is the first known species of endemic to Danxia landform and is currently only known from Mount Danxia, Guangdong.
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http://dx.doi.org/10.3897/phytokeys.185.72788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608780PMC
November 2021

Analysis of the Diagnostic Effect of EUS-RTE on Giant Cystic Tumours of the Oesophagus Based on Cluster Analysis.

J Healthc Eng 2021 3;2021:1395826. Epub 2021 Nov 3.

Department of Endoscopy, The Second People's Hospital of Jiaozuo City, Jiaozuo, Henan 454003, China.

This paper presents an in-depth analysis and study of the diagnostic effectiveness of EUS-RTE in giant cystic tumours of the oesophagus utilizing cluster analysis. A new form of interval data expression was designed based on the cluster analysis algorithm, as well as a new way of updating the cluster radius and cluster centre. Feature triads are defined, eliminating the need to access all historical data at the time of update. It also prevents the case of overfusion of clusters and outputting only one cluster. If there exist a very low number of clusters, the newly merged clusters are reclustered according to the density clustering method for the internal data objects based on the cluster segmentation so that the data objects in the same cluster have a high similarity as possible. All accumulated electronic files of oesophageal cancer cases were collected and comprehensively organized, and all clinical data of 129 eligible cases with a total of 356 consultations were screened in strict accordance with inclusion and exclusion criteria. A database of oesophageal cancer cases was established using Visual FoxPro software, and frequency distribution, cluster analysis, association rule, and chi-square test were used to focus on mining the association between symptoms, disease mechanisms, prescriptions, and medications. The results were analysed and summarized. Overall, the therapeutic efficacy and safety of the three groups of treatment modalities for gastric mesenchymal tumours were positive, and the preoperative endoscopic treatment modalities should be selected based on the EUS-RTE characteristics of the tumour, the site, and the operator's skill level in a comprehensive manner.
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http://dx.doi.org/10.1155/2021/1395826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580657PMC
November 2021

Methyltransferase-Deficient Avian Flaviviruses Are Attenuated Due to Suppression of Viral RNA Translation and Induction of a Higher Innate Immunity.

Front Immunol 2021 6;12:751688. Epub 2021 Oct 6.

Research Centre of Avian Disease, College of Veterinary Medicine of Sichuan Agricultural University, Chengdu, China.

The 5' end of the flavivirus genome contains a type 1 cap structure formed by sequential N-7 and 2'-O methylations by viral methyltransferase (MTase). Cap methylation of flavivirus genome is an essential structural modification to ensure the normal proliferation of the virus. Tembusu virus (TMUV) (genus ) is a causative agent of duck egg drop syndrome and has zoonotic potential. Here, we identified the activity of TMUV MTase and determined the effect of K61-D146-K182-E218 enzymatic tetrad on N-7 and 2'-O methylation. The entire K61-D146-K182-E218 motif is essential for 2'-O MTase activity, whereas N-7 MTase activity requires only D146. To investigate its phenotype, the single point mutation (K61A, D146A, K182A or E218A) was introduced into TMUV replicon (pCMV-Rep-NanoLuc) and TMUV infectious cDNA clone (pACYC-TMUV). K-D-K-E mutations reduced the replication ability of replicon. K61A, K182A and E218A viruses were genetically stable, whereas D146A virus was unstable and reverted to WT virus. Mutant viruses were replication and virulence impaired, showing reduced growth and attenuated cytopathic effects and reduced mortality of duck embryos. Molecular mechanism studies showed that the translation efficiency of mutant viruses was inhibited and a higher host innate immunity was induced. Furthermore, we found that the translation inhibition of MTase-deficient viruses was caused by a defect in N-7 methylation, whereas the absence of 2'-O methylation did not affect viral translation. Taken together, our data validate the debilitating mechanism of MTase-deficient avian flavivirus and reveal an important role for cap-methylation in viral translation, proliferation, and escape from innate immunity.
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http://dx.doi.org/10.3389/fimmu.2021.751688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526935PMC
October 2021

Effects of microbial community and disease resistance against Vibrio splendidus of Yesso scallop (Patinopecten yessoensis) fed supplementary diets of tussah immunoreactive substances and antimicrobial peptides.

Fish Shellfish Immunol 2021 Oct 13. Epub 2021 Oct 13.

Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, 116024, PR China. Electronic address:

This study was conducted to investigate the effects of dietary supplementation of tussah immunoreactive substances (TIS) and antimicrobial peptides (AMPs) on microbial community and resistance against Vibrio splendidus of Yesso scallop Patinopecten yessoensis. Scallops were fed with the basal diets supplemented with TIS (T group), AMPs (A group), or both of the two (TA group). After the feeding trial, the microbial community changes were evaluated, and the challenge test with V. splendidus was conducted, as well as the immune parameters and digestive enzyme activities were determined. The results revealed that the TA group was more capable of modulating the bacterial community composition of scallops by increasing the potentially beneficial bacteria and suppressing the pathogenic microorganism during the feeding trial. After injection, the cumulative mortality rate in TA group was notably lower than others. In addition, the TA group showed better digestive and immune parameters involved in digestive capacity, phagocyte function, phosphatase-responsiveness, and oxidation resistance. These results collectively confirmed that dietary TIS and AMPs in diet could effectively modulate the microflora structure and improve disease resistance against V. splendidus of scallop, and the positive effects were more obvious when dietary supplementation of them in combination.
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http://dx.doi.org/10.1016/j.fsi.2021.10.006DOI Listing
October 2021

Foresight regarding drug candidates acting on the succinate-GPR91 signalling pathway for non-alcoholic steatohepatitis (NASH) treatment.

Biomed Pharmacother 2021 Dec 12;144:112298. Epub 2021 Oct 12.

Hydrogen Medicine Center of Taishan Academy of Medical Sciences, Taian City Central Hospital, Taian 271000, PR China. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. In the pathogenesis of NASH, the signal transduction pathway involving succinate and the succinate receptor (G-protein-coupled receptor 91, GPR91) regulates inflammatory cell activation and liver fibrosis. This review describes the mechanism of the succinate-GPR91 signalling pathway in NASH and summarizes the drugs that act on this pathway, with the aim of providing a new approach to NASH treatment.
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http://dx.doi.org/10.1016/j.biopha.2021.112298DOI Listing
December 2021

Putative Outer Membrane Protein H Affects Virulence.

Front Microbiol 2021 20;12:708225. Epub 2021 Sep 20.

Research Center of Avian Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

causes serious contagious disease in ducks, geese, and other fowl. However, as a harmful pathogen causing significant economic losses in the poultry industry, is still poorly understood for its pathogenesis mechanisms. In a previous study, we developed an indirect ELISA method for detecting infection using B739_0832 protein, a putative outer membrane protein H (OmpH) that is conserved among different serotypes of . Although OmpH in some pathogenic bacteria, such as , has been reported as a virulence factor, it is still not clear whether B739_0832 protein contributes to the virulence of . In this study, we confirmed that B739_0832 protein in localizes to the outer membrane. We constructed a deletion mutant strain (Δ) and assayed various effects from the deletion of B739_0832. Δ0832 strain had a similar growth rate to wild-type CH-1. However, the survival rate of ducklings in 10 days after infection from Δ0832 strain was 50%, whereas no ducklings survived from wild-type infection. Furthermore, the median lethal dose (LD) of the Δ0832 strain was approximately 150 times higher than that of the wild-type strain. Pathology examinations on infected ducklings found that, at 36 h after infection, bacterial loads in blood, liver, and brain tissues from Δ0832-infected ducklings were considerably lower than those from wild-type infected ducklings. These results demonstrate that the B739_0832 protein contributes to the virulence of CH-1.
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http://dx.doi.org/10.3389/fmicb.2021.708225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488386PMC
September 2021

Identification of the Natural Transformation Genes in by Random Transposon Mutagenesis.

Front Microbiol 2021 9;12:712198. Epub 2021 Sep 9.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

In our previous study, it was shown that , a Gram-negative bacterium, is naturally competent, but the genes involved in the process of natural transformation remain largely unknown. In this study, a random transposon mutant library was constructed using the ATCC11845 strain to screen for the genes involved in natural transformation. Among the 3000 insertion mutants, nine mutants had completely lost the ability of natural transformation, and 14 mutants showed a significant decrease in natural transformation frequency. We found that the genes , , , , , , , and are essential for the occurrence of natural transformation in ATCC11845. In particular, , , , and were putatively annotated as ComEC, DprA, ComF, and RecA proteins, respectively, in the NCBI database. However, RA0C_RS02645, RA0C_RS04920, RA0C_RS04915, and RA0C_RS09020 were annotated as proteins with unknown function, with no homology to any well-characterized natural transformation machinery proteins. The homologs of these proteins are mainly distributed in the members of . Taken together, our results suggest that encodes a unique natural transformation machinery.
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http://dx.doi.org/10.3389/fmicb.2021.712198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459023PMC
September 2021

Nuclear localization of duck Tembusu virus NS5 protein attenuates viral replication in vitro and NS5-NS2B3 interaction.

Vet Microbiol 2021 Nov 20;262:109239. Epub 2021 Sep 20.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Wenjiang District, Chengdu City, Sichuan Province, 611130, China. Electronic address:

Duck Tembusu virus (TMUV) belongs to the flavivirus genus whose genome replication involved in capping and RNA synthesis dominating by nonstructural protein 5 (NS5). Flaviviral replication has been well documented to occur in the cytoplasm, but the effect of NS5 to gain access to the nucleus remains controversial. Here, TMUV NS5 was observed to localize within the cytoplasm of transfected and infected cells and co-localized with the endoplasmic reticulum. We introduced two arginine mutations into the N390 and Q392 (N390R and Q392R) of the NS5 bipartite nuclear localization sequence (α/βNLS) and designated that mutagenesis as NS5, which has shown the ability to access the nucleus and hence attenuates viral replication and production in vitro. Additionally, there was no significant difference between the recovered wild-type TMUV (rTMUV-WT) and engineered mutant (rTMUV-NS5) on plaque morphology, survival rate of infected duck embryos or virus copies in tissues. Considering that NS5 is mainly located in the cytoplasm of rTMUV-NS5 infected cells at the early stage of infection. We further confirmed that NS5 attenuated its interaction with nonstructural NS2B-NS3 (NS2B3) following transfection and infection. Meanwhile, the rTMUV-NS5 tended to stimulate more interferon beta (IFNβ) than rTMUV-WT. However, preliminary study on transient NS5 and NS5 detected the same levels of IFNβ mRNA mediated by RIG-I detection of NS5 RNA polymerase activity in cell. In summary, these results provide further insights into the relationship between the viral property and subcellular localization of flavivirus NS5 in terms of the NS5-NS2B3 interaction.
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http://dx.doi.org/10.1016/j.vetmic.2021.109239DOI Listing
November 2021

DR-MIL: deep represented multiple instance learning distinguishes COVID-19 from community-acquired pneumonia in CT images.

Comput Methods Programs Biomed 2021 Nov 9;211:106406. Epub 2021 Sep 9.

Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China. Electronic address:

Background And Objective: Given that the novel coronavirus disease 2019 (COVID-19) has become a pandemic, a method to accurately distinguish COVID-19 from community-acquired pneumonia (CAP) is urgently needed. However, the spatial uncertainty and morphological diversity of COVID-19 lesions in the lungs, and subtle differences with respect to CAP, make differential diagnosis non-trivial.

Methods: We propose a deep represented multiple instance learning (DR-MIL) method to fulfill this task. A 3D volumetric CT scan of one patient is treated as one bag and ten CT slices are selected as the initial instances. For each instance, deep features are extracted from the pre-trained ResNet-50 with fine-tuning and represented as one deep represented instance score (DRIS). Each bag with a DRIS for each initial instance is then input into a citation k-nearest neighbor search to generate the final prediction. A total of 141 COVID-19 and 100 CAP CT scans were used. The performance of DR-MIL is compared with other potential strategies and state-of-the-art models.

Results: DR-MIL displayed an accuracy of 95% and an area under curve of 0.943, which were superior to those observed for comparable methods. COVID-19 and CAP exhibited significant differences in both the DRIS and the spatial pattern of lesions (p<0.001). As a means of content-based image retrieval, DR-MIL can identify images used as key instances, references, and citers for visual interpretation.

Conclusions: DR-MIL can effectively represent the deep characteristics of COVID-19 lesions in CT images and accurately distinguish COVID-19 from CAP in a weakly supervised manner. The resulting DRIS is a useful supplement to visual interpretation of the spatial pattern of lesions when screening for COVID-19.
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http://dx.doi.org/10.1016/j.cmpb.2021.106406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426140PMC
November 2021

Alternative polyadenylation dysregulation contributes to the differentiation block of acute myeloid leukemia.

Blood 2021 Sep 5. Epub 2021 Sep 5.

University of California San Diego, La Jolla, California, United States.

Post-transcriptional regulation has emerged as a driver for leukemia development and an avenue for therapeutic targeting. Among post-transcriptional processes, alternative polyadenylation (APA) is globally dysregulated across cancer types. However, limited studies have focused on the prevalence and role of APA in myeloid leukemia. Furthermore, it is poorly understood how altered poly(A) site (PAS) usage of individual genes contributes to malignancy or whether targeting global APA patterns might alter oncogenic potential. In this study, we examined global APA dysregulation in acute myeloid leukemia (AML) patients by performing 3' Region Extraction And Deep Sequencing (3'READS) on a subset of AML patient samples along with healthy hematopoietic stem and progenitor cells (HSPCs) and by analyzing publicly available data from a broad AML patient cohort. We show that patient cells exhibit global 3' untranslated region (UTR) shortening and coding sequence (CDS) lengthening due to differences in PAS usage. Among APA regulators, expression of FIP1L1, one of the core cleavage and polyadenylation factors, correlated with the degree of APA dysregulation in our 3'READS dataset. Targeting global APA by FIP1L1 knockdown reversed the global trends seen in patients. Importantly, FIP1L1 knockdown induced differentiation of t(8;21) cells by promoting 3'UTR lengthening and downregulation of the fusion oncoprotein AML1-ETO. In non-t(8;21) cells, FIP1L1 knockdown also promoted differentiation by attenuating mTORC1 signaling and reducing MYC protein levels. Our study provides mechanistic insights into the role of APA in AML pathogenesis and indicates that targeting global APA patterns can overcome the differentiation block of AML patients.
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http://dx.doi.org/10.1182/blood.2020005693DOI Listing
September 2021

The Influence of Formulation Components and Environmental Humidity on Spray-Dried Phage Powders for Treatment of Respiratory Infections Caused by .

Pharmaceutics 2021 Jul 28;13(8). Epub 2021 Jul 28.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Shatin, NewTerritories, Hong Kong, China.

The feasibility of using respirable bacteriophage (phage) powder to treat lung infections has been demonstrated in animal models and clinical studies. This work investigated the influence of formulation compositions and excipient concentrations on the aerosol performance and storage stability of phage powder. An anti- phage vB_AbaM-IME-AB406 was incorporated into dry powders consisting of trehalose, mannitol and L-leucine for the first time. The phage stability upon the spray-drying process, room temperature storage and powder dispersion under different humidity conditions were assessed. In general, powders prepared with higher mannitol content (40% of the total solids) showed a lower degree of particle merging and no sense of stickiness during sample handling. These formulations also provided better storage stability of phage with no further titer loss after 1 month and <1 log titer loss in 6 months at high excipient concentration. Mannitol improved the dispersibility of phage powders, but the in vitro lung dose dropped sharply after exposure to high-humidity condition (65% RH) for formulations with 20% mannitol. While previously collected knowledge on phage powder preparation could be largely extended to formulate phage into inhalable dry powders, the environmental humidity may have great impacts on the stability and dispersion of phage; therefore, specific attention is required when optimizing phage powder formulations for global distribution.
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http://dx.doi.org/10.3390/pharmaceutics13081162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401170PMC
July 2021

Effect of Nutritional Determinants and TonB on the Natural Transformation of .

Front Microbiol 2021 10;12:644868. Epub 2021 Aug 10.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

is a gram-negative bacterium that is the first naturally competent bacterium identified in the family . However, the determinants that influence the natural transformation and the underlying mechanism remain unknown. In this study, we evaluated the effects of various nutritional factors of the GCB medium [glucose, L-glutamine, vitamin B1, Fe (NO), NaCl, phosphate, and peptone], on the natural transformation of ATCC 11845. Among the assayed nutrients, peptone and phosphate affected the natural transformation of ATCC 11845, and the transformation frequency was significantly decreased when phosphate or peptone was removed from the GCB medium. When the iron chelator 2,2'-dipyridyl (Dip) was added, the transformation frequency was decreased by approximately 100-fold and restored gradually when Fe (NO) was added, suggesting that the natural transformation of ATCC 11845 requires iron. Given the importance of TonB in nutrient transportation, we further identified whether TonB is involved in the natural transformation of ATCC 11845. Mutation of or , but not , was shown to inhibit the natural transformation of ATCC 11845 in the GCB medium. In parallel, it was shown that the mutant, but not the mutant, decreased iron acquisition in the GCB medium. This result suggested that the mutant affects the natural transformation frequency due to the deficiency of iron utilization.
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http://dx.doi.org/10.3389/fmicb.2021.644868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383284PMC
August 2021

Synthesis of Biomimetic Melanin-Like Multifunctional Nanoparticles for pH Responsive Magnetic Resonance Imaging and Photothermal Therapy.

Nanomaterials (Basel) 2021 Aug 19;11(8). Epub 2021 Aug 19.

Department of Chemistry, Physics and Atmospheric Science, Jackson State University, Jackson, MS 39217, USA.

The design and development of multifunctional nanoparticles have attracted great interest in biomedical research. This study aims to prepare pH-responsive melanin-like nanoparticles for -weighted magnetic resonance imaging (MRI) and photothermal therapy. The new multifunctional nanoparticles (amino-Fe-PDANPs) are synthesized by copolymerization of dopamine and its derivative amino-N-[2-(diethylamino) ethyl]-3,4-dihydroxy-benzenepropanamide (N-Dopa) at room temperature. The size of nanoparticles can be controlled by NaOH concentration. The incorporation of N-Dopa is characterized by NMR and FT-IR. From transmission electron microscopy (TEM), the nanoparticles exhibit excellent dispersion stability in water and are spherical in shape. The MRI measurement has demonstrated that amino-Fe-PDANPs have a significant signal enhancement in responding to the acidic solution. Confirmed by the photothermal study, the nanoparticles exhibit a high photothermal conversion efficiency. The melanin-like multifunctional nanoparticles integrate both diagnosis and therapeutic functionalities, indicating the potential for theranostic application.
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http://dx.doi.org/10.3390/nano11082107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400264PMC
August 2021

Delivery of Phenolic Compounds, Peptides and β-Glucan to the Gastrointestinal Tract by Incorporating Dietary Fibre-Rich Mushrooms into Sorghum Biscuits.

Foods 2021 Aug 5;10(8). Epub 2021 Aug 5.

Department of Wine, Food and Molecular Biosciences, Lincoln University, Christchurch 7647, New Zealand.

Sorghum biscuits were enriched with mushroom powders (, and ) at 5%, 10% and 15% substitution levels. An in vitro gastrointestinal digestion was used to evaluate the effect of this enrichment on the phenolic content and soluble peptide content as well as antioxidant activities of the gastric or intestinal supernatants (bio-accessible fractions), and the remaining portions of phenolic compounds, antioxidants and β-glucan in the undigested residue (non-digestible fraction). The phenolic content of the gastric and intestinal supernatants obtained from digested mushroom-enriched biscuits was found to be higher than that of control biscuit, and the phenolic content was positively correlated to the antioxidant activities in each fraction ( < 0.001). and enrichment increased the soluble protein content (small peptide) of sorghum biscuits after in vitro digestion. All mushroom enrichment increased the total phenolic content and β-glucan content of the undigested residue and they were positively correlated ( < 0.001). The insoluble dietary fibre of biscuits was positively correlated with β-glucan content ( < 0.001) of undigested residue. These findings suggested that enriching food with mushroom derived dietary fibre increases the bioavailability of the non-digestible β-glucan and phenolic compounds.
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http://dx.doi.org/10.3390/foods10081812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391148PMC
August 2021

A viroporin-like 2B protein of duck hepatitis A virus 1 that induces incomplete autophagy in DEF cells.

Poult Sci 2021 Oct 16;100(10):101331. Epub 2021 Jun 16.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, 611130, P.R. China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, 611130, P.R. China; Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, 611130, P.R. China. Electronic address:

Duck hepatitis A virus 1 (DHAV-1) can cause high morbidity and fatal acute infectious hepatitis in ducklings, which seriously endangers animal husbandry. Viroporin is a small molecular weight hydrophobic transmembrane protein encoded by the virus, that has been suggested to induce autophagy in host cells by increasing the membrane permeability through disturbing the ion balance. In this study, we aimed to investigate whether the DHAV-1 2B protein can induce autophagy in DEF cells with a viroporin-like function. Bioinformatics analysis has indicated that the 2B protein is characterized by a viroporin domain, which is consistent with the type IA viroporin transmembrane protein. We experimentally confirmed that the 2B protein disturbed the Ca2+ balance of infected cells by elevating the intracellular Ca2+ concentration. Eukaryotic expression of the 2B protein upregulates the expression of microtubule-associated protein 1 light chain 3 II (LC3-II) and the number of autophagosomes in the cell. Interestingly, the Western Blot (WB) results showed that 2B protein expression induced less protein degradation of the autophagic substrate sequestosome 1 (SQSTM1/p62) than the positive control, while microscopy observations showed that the autophagosomes did not colocalize with the lysosomes. In summary, 2B protein expression induced autophagy in host cells, but the autophagic flow was incomplete. The results of this experiment are expected to provide reference scientific data for elucidating the infective and pathogenic mechanism of DHAV-1.
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http://dx.doi.org/10.1016/j.psj.2021.101331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368021PMC
October 2021

Exploring space-energy matching via quantum-molecular mechanics modeling and breakage dynamics-energy dissipation via microhydrodynamic modeling to improve the screening efficiency of nanosuspension prepared by wet media milling.

Expert Opin Drug Deliv 2021 11 1;18(11):1643-1657. Epub 2021 Sep 1.

Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, P R China.

The preparation of nanosuspensions by wet media milling is a promising technique that increases the bioavailability of insoluble drugs. The nanosuspension is thermodynamically unstable, where its stability might be influenced by the interaction energy between the stabilizers and the drugs after milling at a specific collision energy. However, it is difficult to screen the stabilizers and the parameters of milling accurately and quickly by using traditional analysis methods. Quantum-molecular mechanics and microhydrodynamic modeling can be applied to improve screening efficiency. Quantum-molecular mechanics model, which includes molecular docking, molecular dynamics simulations, and data on binding energy, provides insights into screening stabilizers based on their molecular behavior at the atomic level. The microhydrodynamic model explores the mechanical processes and energy dissipation in nanomilling, and even combines information on the mechanical modulus and an energy vector diagram for the milling parameters screening of drug crystals. These modeling methods improve screening efficiency and support screening theories based on thermodynamics and physical dynamics. However, how to reasonably combine different modeling methods with their theoretical characteristics and further multidimensional and cross-scale simulations of nanosuspension formation remain challenges.
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http://dx.doi.org/10.1080/17425247.2021.1967928DOI Listing
November 2021

The Co-Expression of Melanoma-Antigen Family a Proteins and New York Esophageal Squamous Cell Carcinoma-1 in Breast Cancer: A Pilot Study.

Cancer Manag Res 2021 4;13:6123-6128. Epub 2021 Aug 4.

Department of Clinical Laboratory, Hengshui Fifth People's Hospital, Hengshui City, 053000, People's Republic of China.

Objective: The aim of this study was to quantify the expression of melanoma-antigen family A proteins (MAGE-A) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) in breast cancer and establish the prognosis of breast cancer patients with MAGE-A and NY-ESO-1 co-expression.

Methods: A total of 122 patients with breast cancer were recruited for this study. Their clinicopathological data were collected retrospectively, and the MAGE-A and NY-ESO-1 expressions in paraffin-embedded specimens from the 122 patients were evaluated using immunohistochemical analysis. In addition, the survival states of the patients were recorded.

Results: Fifty-four patients (44.26%) were MAGE-A positive and 46 (37.70%) were NY-ESO-1 positive. Interestingly, 22 of the 46 NY-ESO-1-positive cases co-expressed MAGE-A. The expression of MAGE-A was positively associated with estrogen-receptor status (χ = 4.026, p = 0.045) and human epidermal growth factor receptor 2 status (χ = 5.482, p = 0.019), while the expression of NY-ESO-1 was positively associated with p53 expression (χ = 4.541, p = 0.033). Of the 122 patients, the lowest survival rate was observed in patients with NY-ESO-1 (+)/MAGE-A (+), with a 5-year survival rate of 59.09% and a median survival of 97 months.

Conclusion: The results showed that MAGE-A and NY-ESO-1 were frequently expressed in breast cancer patients. The co-expression of MAGE-A and NY-ESO-1 occurred in about 18% of these patients, and it may indicate a poor prognosis.
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http://dx.doi.org/10.2147/CMAR.S316759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349529PMC
August 2021

MAAPER: model-based analysis of alternative polyadenylation using 3' end-linked reads.

Genome Biol 2021 08 10;22(1):222. Epub 2021 Aug 10.

Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.

Most eukaryotic genes express alternative polyadenylation (APA) isoforms. A growing number of RNA sequencing methods, especially those used for single-cell transcriptome analysis, generate reads close to the polyadenylation site (PAS), termed nearSite reads, hence inherently containing information about APA isoform abundance. Here, we present a probabilistic model-based method named MAAPER to utilize nearSite reads for APA analysis. MAAPER predicts PASs with high accuracy and sensitivity and examines different types of APA events with robust statistics. We show MAAPER's performance with both bulk and single-cell data and its applicability in unpaired or paired experimental designs.
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http://dx.doi.org/10.1186/s13059-021-02429-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356463PMC
August 2021

SCAPTURE: a deep learning-embedded pipeline that captures polyadenylation information from 3' tag-based RNA-seq of single cells.

Genome Biol 2021 08 10;22(1):221. Epub 2021 Aug 10.

CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Single-cell RNA-seq (scRNA-seq) profiles gene expression with high resolution. Here, we develop a stepwise computational method-called SCAPTURE to identify, evaluate, and quantify cleavage and polyadenylation sites (PASs) from 3' tag-based scRNA-seq. SCAPTURE detects PASs de novo in single cells with high sensitivity and accuracy, enabling detection of previously unannotated PASs. Quantified alternative PAS transcripts refine cell identity analysis beyond gene expression, enriching information extracted from scRNA-seq data. Using SCAPTURE, we show changes of PAS usage in PBMCs from infected versus healthy individuals at single-cell resolution.
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http://dx.doi.org/10.1186/s13059-021-02437-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353616PMC
August 2021

Updates on the global dissemination of colistin-resistant Escherichia coli: An emerging threat to public health.

Sci Total Environ 2021 Dec 27;799:149280. Epub 2021 Jul 27.

Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China. Electronic address:

Colistin drug resistance is an emerging public health threat worldwide. The adaptability, existence and spread of colistin drug resistance in multiple reservoirs and ecological environmental settings is significantly increasing the rate of occurrence of multidrug resistant (MDR) bacteria such as Escherichia coli (E. coli). Here, we summarized the reports regarding molecular and biological characterization of mobile colistin resistance gene (mcr)-positive E. coli (MCRPEC), originating from diverse reservoirs, including but not limited to humans, environment, waste water treatment plants, wild, pets, and food producing animals. The MCRPEC revealed the abundance of clinically important resistance genes, which are responsible for MDR profile. A number of plasmid replicon types such as IncI2, IncX4, IncP, IncX, and IncFII with a predominance of IncI2 were facilitating the spread of colistin resistance. This study concludes the distribution of multiple sequence types of E. coli carrying mcr gene variants, which are possible threat to "One Health" perspective. In addition, we have briefly explained the newly known mechanisms of colistin resistance i.e. plasmid-encoded resistance determinant as well as presented the chromosomally-encoded resistance mechanisms. The transposition of ISApl1 into the chromosome and existence of intact Tn6330 are important for transmission and stability for mcr gene. Further, genetic environment of co-localized mcr gene with carbapenem-resistance or extended-spectrum β-lactamases genes has also been elaborated, which is limiting human beings to choose last resort antibiotics. Finally, environmental health and safety control measures along with spread mechanisms of mcr genes are discussed to avoid further propagation and environmental hazards of colistin resistance.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149280DOI Listing
December 2021

Alternative 3' UTRs play a widespread role in translation-independent mRNA association with the endoplasmic reticulum.

Cell Rep 2021 Jul;36(3):109407

Program in Gene Expression and Regulation and Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA 19104, USA; Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; Graduate Program in Quantitative Biomedicine, School of Graduate Studies, Rutgers University, Piscataway, NJ 08854, USA; Rutgers School of Graduate Studies, Newark, NJ 07103, USA. Electronic address:

Transcripts encoding membrane and secreted proteins are known to associate with the endoplasmic reticulum (ER) through translation. Here, using cell fractionation, polysome profiling, and 3' end sequencing, we show that transcripts differ substantially in translation-independent ER association (TiERA). Genes in certain functional groups, such as cell signaling, tend to have significantly higher TiERA potentials than others, suggesting the importance of ER association for their mRNA metabolism, such as localized translation. The TiERA potential of a transcript is determined largely by size, sequence content, and RNA structures. Alternative polyadenylation (APA) isoforms can have distinct TiERA potentials because of changes in transcript features. The widespread 3' UTR lengthening in cell differentiation leads to greater transcript association with the ER, especially for genes that are capable of expressing very long 3' UTRs. Our data also indicate that TiERA is in dynamic competition with translation-dependent ER association, suggesting limited space on the ER for mRNA association.
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http://dx.doi.org/10.1016/j.celrep.2021.109407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501909PMC
July 2021

The influence of growth conditions on MALDI-TOF MS spectra of winemaking yeast: implications for industry applications.

J Microbiol Methods 2021 09 15;188:106280. Epub 2021 Jul 15.

Department of Wine, Food and Molecular Biosciences, Lincoln University, PO Box 85054, Lincoln, New Zealand. Electronic address:

Previous studies have shown MALDI-TOF MS to be a powerful tool in wine yeast identification and potential prediction of application. However, it is also established that substrate composition influences protein expression, but the degree to which this may affect MALDI-TOF spectra (and analytical results thereof) has not been fully explored. To further inform assay optimisation, the influence on MALDI-TOF spectra was determined using eight Saccharomyces strains of diverse origins cultivated on grape juices from Pinot Noir and Chardonnay varieties, synthetic grape juice, and laboratory-grade artificial culture media (YPD broth and agar). Our results demonstrated significant influences of culture media on strain MALDI-TOF spectra. Yeast culture on YPD agar is recommended for taxonomic studies, with YPD broth culture of S. cerevisiae offering improved intra-subspecific differentiation Furthermore, our data supported a correlation between MALDI spectra and the potential industrial application of individual yeast strains.
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http://dx.doi.org/10.1016/j.mimet.2021.106280DOI Listing
September 2021

Expanding the range of editable targets in the wheat genome using the variants of the Cas12a and Cas9 nucleases.

Plant Biotechnol J 2021 Dec 28;19(12):2428-2441. Epub 2021 Jul 28.

Department of Plant Pathology, Kansas State University, Manhattan, KS, USA.

The development of CRISPR-based editors recognizing distinct protospacer-adjacent motifs (PAMs), or having different spacer length/structure requirements broadens the range of possible genomic applications. We evaluated the natural and engineered variants of Cas12a (FnCas12a and LbCas12a) and Cas9 for their ability to induce mutations in endogenous genes controlling important agronomic traits in wheat. Unlike FnCas12a, LbCas12a-induced mutations in the wheat genome, even though with a lower rate than that reported for SpCas9. The eight-fold improvement in the gene editing efficiency was achieved for LbCas12a by using the guides flanked by ribozymes and driven by the RNA polymerase II promoter from switchgrass. The efficiency of multiplexed genome editing (MGE) using LbCas12a was mostly similar to that obtained using the simplex RNA guides and showed substantial increase after subjecting transgenic plants to high-temperature treatment. We successfully applied LbCas12a-MGE for generating heritable mutations in a gene controlling grain size and weight in wheat. We showed that the range of editable loci in the wheat genome could be further expanded by using the engineered variants of Cas12a (LbCas12a-RVR) and Cas9 (Cas9-NG and xCas9) that recognize the TATV and NG PAMs, respectively, with the Cas9-NG showing higher editing efficiency on the targets with atypical PAMs compared to xCas9. In conclusion, our study reports a set of validated natural and engineered variants of Cas12a and Cas9 editors for targeting loci in the wheat genome not amenable to modification using the original SpCas9 nuclease.
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http://dx.doi.org/10.1111/pbi.13669DOI Listing
December 2021

Murine Ifit3 restricts the replication of Rabies virus both and .

J Gen Virol 2021 07;102(7)

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.

Rabies virus (RABV) infection can initiate the host immune defence response and induce an antiviral state characterized by the expression of interferon (IFN)-stimulated genes (ISGs), among which the family of genes of IFN-induced protein with tetratricopeptide repeats (Ifits) are prominent representatives. Herein, we demonstrated that the mRNA and protein levels of Ifit1, Ifit2 and Ifit3 were highly increased in cultured cells and mouse brains after RABV infection. Recombinant RABV expressing Ifit3, designated rRABV-Ifit3, displayed a lower pathogenicity than the parent RABV in C57BL/6 mice after intramuscular administration, and Ifit3-deficient mice exhibited higher susceptibility to RABV infection and higher mortality during RABV infection. Moreover, compared with their individual expressions, co-expression of Ifit2 and Ifit3 could more effectively inhibit RABV replication . These results indicate that murine Ifit3 plays an essential role in restricting the replication and reducing the pathogenicity of RABV. Ifit3 acts synergistically with Ifit2 to inhibit RABV replication, providing further insight into the function and complexity of the Ifit family.
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http://dx.doi.org/10.1099/jgv.0.001619DOI Listing
July 2021

CRISPRpas: programmable regulation of alternative polyadenylation by dCas9.

Nucleic Acids Res 2021 Jul 9. Epub 2021 Jul 9.

Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.

Most human protein-coding genes produce alternative polyadenylation (APA) isoforms that differ in 3' UTR size or, when coupled with splicing, have variable coding sequences. APA is an important layer of gene expression program critical for defining cell identity. Here, by using a catalytically dead Cas9 and coupling its target site with polyadenylation site (PAS), we develop a method, named CRISPRpas, to alter APA isoform abundance. CRISPRpas functions by enhancing proximal PAS usage, whose efficiency is influenced by several factors, including targeting strand of DNA, distance between PAS and target sequence and strength of the PAS. For intronic polyadenylation (IPA), splicing features, such as strengths of 5' splice site and 3' splice site, also affect CRISPRpas efficiency. We show modulation of APA of multiple endogenous genes, including IPA of PCF11, a master regulator of APA and gene expression. In sum, CRISPRpas offers a programmable tool for APA regulation that impacts gene expression.
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http://dx.doi.org/10.1093/nar/gkab519DOI Listing
July 2021

High incidence of multi-drug resistance and heterogeneity of mobile genetic elements in Escherichia coli isolates from diseased ducks in Sichuan province of China.

Ecotoxicol Environ Saf 2021 Oct 6;222:112475. Epub 2021 Jul 6.

Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China. Electronic address:

Harmonious ecological environment is a major concern with rising feeding and consumption of ducks, as these waterfowl birds can promote the spread of antibiotic resistant genes (ARGs). Therefore, this study was conducted to know diversity of antimicrobial resistance (AMR), integrons, and mobile genetic elements (MGEs) in Escherichia coli (E. coli) isolated from intestinal contents or pericardial effusion of diseased ducks from 2018 to 2020 in Sichuan, China. The AMR phenotype was determined via disk diffusion test in 165 E. coli isolates. Further, the integrase genes of integron (intI1, intI2 and intI3 genes), gene cassettes (GCs) and MGEs were screened by PCR and sequencing. The results indicated 100% isolates were resistant to at least one antibiotic and 98.8% were multidrug-resistant strains. Highest AMR phenotype was recorded to rifampin (97.0%) followed by ampicillin (95.8%), chloramphenicol (89.7%), trimethoprim-sulfamethoxazole (84.2%), ciprofloxacin (83.0%), cefotaxime (80.0%), streptomycin (75.8%), doxycycline (49.7%), amikacin (10.3%), amoxicillin/clavulanic acid (3.6%), polymyxin B (1.2%) and ertapenem (0.6%). Further, class 1 and 2 integrons were found in 87.3% and 17.6% isolates, respectively. All isolates were negative for intI3 gene. The variable region of class 1 and 2 integrons contained total 13 different GCs, including arr-3+dfrA27, dfrA1+aadA1, dfrA17+aadA5, dfrA12, dfrA1+sat2+aadA1, dfrA12+aadA2, dfrA5, aadA2+ere(A)+dfrA32, aac(6')-Ib-cr, aadA22, aadA5, dfrA17, and dfrA27. Moreover, 13 MGEs in 69 different combinations were observed with predominance of IS26 followed by tnpA/Tn21, trbC, ISEcp1, merA, ISAba1, tnsA, tnsB, tnsC, IS1133, tnsD, ISCR3/14, and tnsE. Thus, the monitoring of integrons, MGEs and ARGs is important to understand the complex mechanism of AMR, which might help to introduce interventions for prevention and control of AMR in duck farms in China.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112475DOI Listing
October 2021

Preface.

Authors:
Bin Tian

Methods Enzymol 2021 ;655:xix-xx

Gene Expression and Regulation Program, Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA, United States.

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http://dx.doi.org/10.1016/S0076-6879(21)00309-8DOI Listing
July 2021
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