27,038 results match your criteria conformational change

Natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

Drug Discovery and Design Center, the Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Read More

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Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis.

Nat Commun 2021 04 13;12(1):2211. Epub 2021 Apr 13.

Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

Phosphorylation of the MLKL pseudokinase by the RIPK3 kinase leads to MLKL oligomerization, translocation to, and permeabilization of, the plasma membrane to induce necroptotic cell death. The precise choreography of MLKL activation remains incompletely understood. Here, we report Monobodies, synthetic binding proteins, that bind the pseudokinase domain of MLKL within human cells and their crystal structures in complex with the human MLKL pseudokinase domain. Read More

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Generation of Fluorescent Versions of Saccharomyces cerevisiae RPA to Study the Conformational Dynamics of Its ssDNA-Binding Domains.

Methods Mol Biol 2021 ;2281:151-168

Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, USA.

Replication protein A (RPA) is an essential single-stranded DNA (ssDNA)-binding protein that sequesters ssDNA and protects it from nucleolytic degradation. The RPA-ssDNA nucleoprotein acts as a hub to recruit over two dozen DNA metabolic enzymes onto ssDNA to coordinate DNA replication, repair, and recombination. RPA functions as a heterotrimer composed of RPA70, RPA32, and RPA14 subunits and has multiple DNA-binding and protein-interaction domains. Read More

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January 2021

Photocontrolled Nanopipette Biosensor for ATP Gradient Electroanalysis of Single Living Cells.

ACS Sens 2021 Apr 13. Epub 2021 Apr 13.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.

Emerging nanopipette tools have demonstrated substantial potential for advanced single-cell analysis, which plays vital roles from fundamental cellular biology to biomedical diagnostics. Highly recyclable nanopipettes with easy and quick regeneration are of special interest for precise and multiple measurements. However, existing recycle strategies are generally plagued by operational complexity and limited efficiency. Read More

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Potential aggregation hot spots in recombinant human keratinocyte growth factor: a computational study.

J Biomol Struct Dyn 2021 Apr 10:1-16. Epub 2021 Apr 10.

Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.

The recombinant human keratinocyte growth factor (rhKGF) is a highly aggregation-prone therapeutic protein. The high aggregation liability of rhKGF is manifested by loss of the monomeric state, and accumulation of the aggregated species even at moderate temperatures. Here, we analyzed the rhKGF for its vulnerability toward aggregation by detection of aggregation-prone regions (APRs) using several sequence-based computational tools including TANGO, ZipperDB, AGGRESCAN, Zyggregator, Camsol, PASTA, SALSA, WALTZ, SODA, Amylpred, AMYPDB, and structure-based tools including SolubiS, CamSol structurally corrected, Aggrescan3D and spatial aggregation propensity (SAP) algorithm. Read More

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Structure of an ancestral ADP-dependent kinase with fructose-6P reveals key residues for binding, catalysis, and ligand-induced conformational changes.

J Biol Chem 2020 Dec 24;296:100219. Epub 2020 Dec 24.

Laboratorio de Bioquímica y Biología Molecular, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. Electronic address:

ADP-dependent kinases were first described in archaea, although their presence has also been reported in bacteria and eukaryotes (human and mouse). This enzyme family comprises three substrate specificities; specific phosphofructokinases (ADP-PFKs), specific glucokinases (ADP-GKs), and bifunctional enzymes (ADP-PFK/GK). Although many structures are available for members of this family, none exhibits fructose-6-phosphate (F6P) at the active site. Read More

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December 2020

Paramount Importance of Core Conformational Changes for Heparin Allosteric Activation of Antithrombin.

Biochemistry 2021 Apr 6. Epub 2021 Apr 6.

Antithrombin is unique among serpin family protein protease inhibitors with respect to the major reactive center loop (RCL) and core conformational changes that mediate allosteric activation of its anticoagulant function by heparin. A critical role for expulsion of the RCL hinge from a native stabilizing interaction with the hydrophobic core in the activation mechanism has been proposed from reports that antithrombin variants that block this change through engineered disulfide bonds block activation. However, the sufficiency of core conformational changes for activation without expulsion of the RCL from the core is suggested by variants that are activated without the need for heparin and retain the native RCL-core interaction. Read More

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The selection process of licensing a DNA mismatch for repair.

Nat Struct Mol Biol 2021 Apr 5. Epub 2021 Apr 5.

MRC Laboratory of Medical Research, Cambridge, UK.

DNA mismatch repair detects and removes mismatches from DNA by a conserved mechanism, reducing the error rate of DNA replication by 100- to 1,000-fold. In this process, MutS homologs scan DNA, recognize mismatches and initiate repair. How the MutS homologs selectively license repair of a mismatch among millions of matched base pairs is not understood. Read More

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Investigation on conformational variation and activity of trypsin affected by black phosphorus quantum dots via multi-spectroscopy and molecular modeling.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 26;256:119746. Epub 2021 Mar 26.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, College of Chemistry and Materials, Nanning Normal University, Nanning 530001, PR China. Electronic address:

Binding interaction between black phosphorus quantum dots (BPQDs) and trypsin was researched deeply to illustrate the variations on conformation and activity of trypsin affected by BPQDs via multi-spectroscopy and molecular modeling. Experimental results implied that inherent fluorescence of trypsin was quenched by BPQDs via static fluorescence quenching mode. BPQDs bound with trypsin to construct ground-state complex under the binding forces of van der Waal interaction and hydrophobic interaction, resulting in the conformational change of trypsin to be more hydrophilic and incompact. Read More

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Crystal structures of LeuT reveal conformational dynamics in the outward-facing states.

J Biol Chem 2021 Apr 1:100609. Epub 2021 Apr 1.

Department of Integrated Traditional Chinese and Western Medicine, Rare Diseases Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address:

The neurotransmitter:sodium symporter (NSS) homolog LeuT from Aquifex aeolicus has proven to be a valuable model for studying the transport mechanism of the NSS family. Crystal structures have captured LeuT in key conformations visited during the transport cycle, allowing for the construction of a nearly complete model of transport, with much of the conformational dynamics studied by computational simulations. Here, we report crystal structures of LeuT representing new intermediate conformations between the outward-facing open and occluded states. Read More

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A Label-Free Liquid Crystal Biosensor Based on Specific DNA Aptamer Probes for Sensitive Detection of Amoxicillin Antibiotic.

Micromachines (Basel) 2021 Mar 30;12(4). Epub 2021 Mar 30.

Department of Chemistry, Gachon University, Seongnam-daero 1342, Sujeong-gu, Seongnam-si, Gyeonggi-do 13120, Korea.

We developed a liquid crystal (LC) aptamer biosensor for the sensitive detection of amoxicillin (AMX). The AMX aptamer was immobilized onto the surface of a glass slide modified with a mixed self-assembled layer of dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride (DMOAP) and (3-aminopropyl) triethoxysilane (APTES). The long alkyl chains of DMOAP maintained the LC molecules in a homeotropic orientation and induced a dark optical appearance under a polarized light microscope (POM). Read More

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Potential Target Site for Inhibitors in MLS Antibiotic Resistance.

Antibiotics (Basel) 2021 Mar 5;10(3). Epub 2021 Mar 5.

Department of Bioscience and Biotechnology, The University of Suwon, Whasung City 18323, Korea.

Macrolide-lincosamide-streptogramin B antibiotic resistance occurs through the action of erythromycin ribosome methylation (Erm) family proteins, causing problems due to their prevalence and high minimal inhibitory concentration, and feasibilities have been sought to develop inhibitors. Erms exhibit high conservation next to the N-terminal end region (NTER) as in ErmS, 64SQNF67. Side chains of homologous S, Q and F in ErmC' are surface-exposed, located closely together and exhibit intrinsic flexibility; these residues form a motif X. Read More

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A Cationic Surfactant-Decorated Liquid Crystal-Based Aptasensor for Label-Free Detection of Malathion Pesticides in Environmental Samples.

Biosensors (Basel) 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of Chemistry, Gachon University, Seongnam-daero 1342, Sujeong-gu, Seongnam-si 13120, Gyeonggi-do, Korea.

We report a liquid crystal (LC)-based aptasensor for the detection of malathion using a cationic surfactant-decorated LC interface. In this method, LCs displayed dark optical images when in contact with aqueous cetyltrimethylammonium bromide (CTAB) solution due to the formation of a self-assembled CTAB monolayer at the aqueous/LC interface, which induced the homeotropic orientation of LCs. With the addition of malathion aptamer, the homeotropic orientation of LCs changed to a planar one due to the interactions between CTAB and the aptamer, resulting in a bright optical image. Read More

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Classical and Atypical Scrapie in Sheep and Goats. Review on the Etiology, Genetic Factors, Pathogenesis, Diagnosis, and Control Measures of Both Diseases.

Animals (Basel) 2021 Mar 4;11(3). Epub 2021 Mar 4.

Research Centre for TSE and Emerging Transmissible Diseases, Veterinary Faculty C/Miguel Servet 177, Universidad de Zaragoza, 50013 Zaragoza, Spain.

Prion diseases, such as scrapie, are neurodegenerative diseases with a fatal outcome, caused by a conformational change of the cellular prion protein (PrP), originating with the pathogenic form (PrP). Classical scrapie in small ruminants is the paradigm of prion diseases, as it was the first transmissible spongiform encephalopathy (TSE) described and is the most studied. It is necessary to understand the etiological properties, the relevance of the transmission pathways, the infectivity of the tissues, and how we can improve the detection of the prion protein to encourage detection of the disease. Read More

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Graphene Oxide-Induced Protein Conformational Change in Nasopharyngeal Carcinoma Cells: A Joint Research on Cytotoxicity and Photon Therapy.

Materials (Basel) 2021 Mar 13;14(6). Epub 2021 Mar 13.

Department of Chemical and Materials Engineering, Chang Gung University, Wenhua 1st Road, Guishan, Taoyuan 333, Taiwan.

The objectives of this work aim to investigate the interaction and cytotoxicity between nanometric graphene oxide (GO) and nasopharyngeal carcinoma cells (NPC-BM1), and possible application in photon therapy. GO nanosheets were obtained in the size range of 100-200 nm, with a negative surface charge. This nanometric GO exhibited a limited (<10%) cytotoxicity effect and no significant dimensional change on NPC-BM1 cells in the tested GO concentration range (0. Read More

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Riboswitch control of bacterial RNA stability.

Mol Microbiol 2021 Apr 2. Epub 2021 Apr 2.

Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY, 10016, USA.

Although riboswitches have long been known to regulate translation initiation and transcription termination, a growing body of evidence indicates that they can also control bacterial RNA lifetimes by acting directly to hasten or impede RNA degradation. Ligand binding to the aptamer domain of a riboswitch can accelerate RNA decay by triggering a conformational change that exposes sites to endonucleolytic cleavage or by catalyzing the self-cleavage of a prefolded ribozyme. Alternatively, the conformational change induced by ligand binding can protect RNA from degradation by blocking access to an RNA terminus or internal region that would otherwise be susceptible to attack by an exonuclease or an endonuclease. Read More

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Structure of detergent-activated BAK dimers derived from the inert monomer.

Mol Cell 2021 Mar 23. Epub 2021 Mar 23.

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address:

A body of data supports the existence of core (α2-α5) dimers of BAK and BAX in the oligomeric, membrane-perturbing conformation of these essential apoptotic effector molecules. Molecular structures for these dimers have only been captured for truncated constructs encompassing the core domain alone. Here, we report a crystal structure of BAK α2-α8 dimers (i. Read More

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Multiple Sites on SARS-CoV-2 Spike Protein are Susceptible to Proteolysis by Cathepsins B, K, L, S, and V.

Protein Sci 2021 Mar 31. Epub 2021 Mar 31.

Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology & Emory University.

SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Proteases are central to the infection process of SARS-CoV-2. Cleavage of the spike protein on the virus's capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Read More

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Crystal structures of REF6 and its complex with DNA reveal diverse recognition mechanisms.

Cell Discov 2020 Mar 31;6(1):17. Epub 2020 Mar 31.

State Key Laboratory of Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, 100193, Beijing, China.

Relative of Early Flowing 6 (REF6) is a DNA-sequence-specific H3K27me3/2 demethylase that contains four zinc finger (ZnF) domains and targets several thousand genes in Arabidopsis thaliana. The ZnF domains are essential for binding target genes, but the structural basis remains unclear. Here, we determined crystal structures of the ZnF domains and REF6-DNA complex, revealing a unique REF6-family-specific half-cross-braced ZnF (RCZ) domain and two C2H2-type ZnFs. Read More

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Structural analyses of an RNA stability element interacting with poly(A).

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536;

Cis-acting RNA elements are crucial for the regulation of polyadenylated RNA stability. The element for nuclear expression (ENE) contains a U-rich internal loop flanked by short helices. An ENE stabilizes RNA by sequestering the poly(A) tail via formation of a triplex structure that inhibits a rapid deadenylation-dependent decay pathway. Read More

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Microfluidic Integrated Organic Electrochemical Transistor with a Nanoporous Membrane for Amyloid-β Detection.

ACS Nano 2021 Mar 30. Epub 2021 Mar 30.

Biological and Environmental Science and Engineering (BESE), Organic Bioelectronics Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with a severe loss in thinking, learning, and memory functions of the brain. To date, no specific treatment has been proven to cure AD, with the early diagnosis being vital for mitigating symptoms. A common pathological change found in AD-affected brains is the accumulation of a protein named amyloid-β (Aβ) into plaques. Read More

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Non-covalently embedded oxytocin in alkanethiol monolayer as Zn selective biosensor.

Sci Rep 2021 Mar 29;11(1):7051. Epub 2021 Mar 29.

The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, 91904, Jerusalem, Israel.

Peptides are commonly used as biosensors for analytes such as metal ions as they have natural binding preferences. In our previous peptide-based impedimetric metal ion biosensors, a monolayer of the peptide was anchored covalently to the electrode. Binding of metal ions resulted in a conformational change of the oxytocin peptide in the monolayer, which was measured using electrochemical impedance spectroscopy. Read More

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Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated K channel.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Graduate Program in Biophysics, University of Wisconsin-Madison, Madison, WI 53706;

Temperature-dependent regulation of ion channel activity is critical for a variety of physiological processes ranging from immune response to perception of noxious stimuli. Our understanding of the structural mechanisms that underlie temperature sensing remains limited, in part due to the difficulty of combining high-resolution structural analysis with temperature stimulus. Here, we use NMR to compare the temperature-dependent behavior of Shaker potassium channel voltage sensor domain (WT-VSD) to its engineered temperature sensitive (TS-VSD) variant. Read More

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The CFTR P67L variant reveals a key role for N-terminal lasso helices in channel folding, maturation, and pharmacologic rescue.

J Biol Chem 2021 Mar 26:100598. Epub 2021 Mar 26.

Emory University, Atlanta, GA 30322.

Patients with cystic fibrosis (CF) harboring the P67L variant in the CF transmembrane conductance regulator (CFTR) often exhibit a typical CF phenotype, including severe respiratory compromise. This rare mutation (reported in <300 patients worldwide) responds robustly to CFTR correctors such as lumacaftor and tezacaftor, with rescue in model systems that far exceeds what can be achieved for the archetypical CFTR mutant F508del. However, the specific molecular consequences of the P67L mutation are poorly characterized. Read More

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Study on the interaction of three classical drugs used in psychiatry in albumin through spectrofluorimetric modeling.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 5;255:119638. Epub 2021 Mar 5.

Rio de Janeiro State University, Av. Manoel de Abreu, 444, Rio de Janeiro 20550-171, Brazil; Department of Applied Mathematics, Rio de Janeiro State University, Rua São Francisco Xavier, 524, Rio de Janeiro 20559-900, Brazil. Electronic address:

Comparative study of haloperidol (HPD), biperiden (BPD) and clonazepam (CNZ) interactions with human and bovine serum albumin was performed based on fluorescence quenching analysis. We used mathematical modeling comparing spectrofluorimetric data to obtain information on the possibility of competition among three drugs by sites binding. Results showed that the three drugs studied have high affinity for albumin and suggest the existence of two site classes in HSA for HPD and only one class for BPD and CNZ, in the range of concentrations tested for each drug. Read More

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Production of self-assembling acylated ovalbumin nanogels as stable delivery vehicles for curcumin.

Food Chem 2021 Mar 20;355:129635. Epub 2021 Mar 20.

National Research and Development Center for Egg Processing, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.

In this study, we evaluated potential usage of acylated ovalbumin (AOVA) nanogels fabricated via acylation modification and heat-induced self-assembly process as novel delivery systems for curcumin. Compared to native ovalbumin (NOVA) nanogels without chemical acylation, the obtained AOVA nanogels have shown smaller average hydrodynamic diameter (155.73 nm), relatively uniform size distribution (polydispersity index around 0. Read More

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Functional and conformational impact of cancer-associated mutations depends on the position and the charge of amino acid substitution.

Comput Struct Biotechnol J 2021 27;19:1361-1370. Epub 2021 Feb 27.

Institut Curie, PSL Research University, Uveal Melanoma Group, Translational Research Department, Paris, France.

The hotspot mutations of , the most frequently mutated splicing gene in cancers, contribute to oncogenesis by corrupting the mRNA splicing Further mutations have been reported in cancers but their consequences remain unclear. Here, we screened for mutations in the vicinity of the hotspot region in tumors. We then performed prediction of the functional outcome followed by modelling of different SF3B1 mutants. Read More

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February 2021

The structural basis of Akt PH domain interaction with calmodulin.

Biophys J 2021 Mar 26. Epub 2021 Mar 26.

Department of Computer Engineering, Koç University, Istanbul, Turkey. Electronic address:

Akt plays a key role in the Ras/PI3K/Akt/mTOR signaling pathway. In breast cancer, Akt translocation to the plasma membrane is enabled by the interaction of its pleckstrin homology domain (PHD) with calmodulin (CaM). At the membrane, the conformational change promoted by PIP releases CaM and facilitates Thr308 and Ser473 phosphorylation and activation. Read More

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Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach.

Infect Genet Evol 2021 Mar 24;91:104815. Epub 2021 Mar 24.

Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana; Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.

The D614G variant of SARS-CoV-2 S-protein emerged in early 2020 and quickly became the dominant circulating strain in Europe and its environs. The variant was characterized by the higher viral load, which is not associated with disease severity, higher incorporation into the virion, and high cell entry via ACE-2 and TMPRSS2. Previous strains of the coronavirus and the current SARS-CoV-2 have demonstrated the selection of mutations as a mechanism of escaping immune responses. Read More

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Development of mouse monoclonal antibody for detecting hemagglutinin of avian influenza A(H7N9) virus and preventing virus infection.

Appl Microbiol Biotechnol 2021 Mar 26. Epub 2021 Mar 26.

Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, 106, Taiwan.

Many cases of avian influenza A(H7N9) virus infection in humans have been reported since its first emergence in 2013. The disease is of concern because most patients have become severely ill with roughly 30% mortality rate. Because the threat in public health caused by H7N9 virus remains high, advance preparedness is essentially needed. Read More

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