Skip to main content

linfeng cheng

Followers

3

Following

1

Public Views

C. Michael Hall

University of Canterbury/Te Whare Wānanga o Waitaha

Free University of Bozen-Bolzano

University of Algarve

Universidade de Évora

Mehmet Akif Ersoy University

Hacettepe University

Monika Kaczmarek-Śliwińska

University of Warsaw

Ganga S Dhanesh

Zayed University

University of Surrey

Ankara Hacı Bayram Veli University

Interests

Uploads

Papers by linfeng cheng

An algal lectin griffithsin inhibits Hantaan virus infection in vitro and in vivo

Frontiers in Cellular and Infection Microbiology

Hantaan virus (HTNV) is the etiological pathogen of hemorrhagic fever with renal syndrome in East... more Hantaan virus (HTNV) is the etiological pathogen of hemorrhagic fever with renal syndrome in East Asia. There are currently no effective therapeutics approved for HTNV and other hantavirus infections. We found that griffithsin (GRFT), an algae-derived lectin with broad-spectrum antiviral activity against various enveloped viruses, can inhibit the growth and spread of HTNV. In vitro experiments using recombinant vesicular stomatitis virus (rVSV) with HTNV glycoproteins as a model revealed that the GRFT inhibited the entry of rVSV-HTNV-G into host cells. In addition, we demonstrated that GRFT prevented authentic HTNV infection in vitro by binding to the viral N-glycans. In vivo experiments showed that GRFT partially protected the suckling mice from death induced by intracranial exposure to HTNV. These results demonstrated that GRFT can be a promising agent for inhibiting HTNV infection.

Dihydropyridine-derived calcium channel blocker as a promising anti-hantavirus entry inhibitor

Frontiers in Pharmacology

Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with ren... more Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are distributed from Eurasia to America. HFRS and HPS have mortality rates of up to 15% or 45%, respectively. Currently, no certified therapeutic has been licensed to treat hantavirus infection. In this study, we discovered that benidipine hydrochloride, a calcium channel blocker, inhibits the entry of hantaviruses in vitro. Moreover, an array of calcium channel inhibitors, such as cilnidipine, felodipine, amlodipine, manidipine, nicardipine, and nisoldipine, exhibit similar antiviral properties. Using pseudotyped vesicular stomatitis viruses harboring the different hantavirus glycoproteins, we demonstrate that benidipine hydrochloride inhibits the infection by both HFRS- and HPS-causing hantaviruses. The results of our study indicate the possibility of repurposing FDA-approved calcium channel blockers for the treatment of hanta...

A laboratory study on the dielectric spectroscopy of sandstone and the improvement of dispersion model

Journal of Petroleum Science and Engineering

LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

Frontiers in Microbiology

As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and is ... more As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and is the leading causative agent of severe hemorrhagic fever with renal syndrome (HFRS), which has profound morbidity and mortality. Macrophages are crucial components of the host innate immune system and serve as the first line of defense against HTNV infection. Previous studies indicated that the viral replication efficiency in macrophages determines hantavirus pathogenicity, but it remains unknown which factor manipulates the macrophage activation pattern and the virus-host interaction process. Here, we performed the transcriptomic analysis of HTNV-infected mouse bone marrow-derived macrophages and identified the long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1), especially the isoform NEAT1-2, as one of the lncRNAs that is differentially expressed at the early phase. Based on coculture experiments, we revealed that silencing NEAT1-2 hinders inflammatory macrophage...

[Establishment of an immortalized human umbilical vein endothelial cell line used for the study of the innate immune response to Hantaan virus]

Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, 2021

Objective To establish the immortalized human umbilical vein vascular endothelial cells (HUVECs-h... more Objective To establish the immortalized human umbilical vein vascular endothelial cells (HUVECs-hTERT) by introducing hTERT gene into primary HUVECs. In order to evaluate the potential of HUVECs-hTERT as a research model of HTNV infection, we explored the infection efficiency of Hantaan virus (HTNV) in HUVECs-hTERT and the influence of celluar innate immune regulation. Methods hTERT gene was cloned into lentivirus vector pCDH-CMV-MCS-EF1-puro, resulting in pCDH-CMV-hTERT-EF1-puro plasmid which was packaged into lentivirus. Then it was infected with HUVECs, and the HUVECs which stably express hTERT gene was selected by using puromycin and named HUVECs-hTERT. The morphology of HUVECs-hTERT and endothelial cell marker molecules, such as human von Willebrand factor (vWF), CD31 and vascular endothelial cell cadherin (VE-cadherin) were identified by microscopic observation and immunofluorescence assay. The percentage of nucleocapsid protein (NP)-positive cells after HTNV infection was det...

Differential Macrophage Phenotype Rewired by Hantaan Virus Constrains the Magnitude of Inflammatory Responses in Murine versus Humans

Hantaan virus (HTNV) is principally maintained and transmitted by rodents in nature, the infectio... more Hantaan virus (HTNV) is principally maintained and transmitted by rodents in nature, the infection of which is non-pathogenic in the field or laboratory mouse, but can cause hemorrhagic fever with renal syndrome (HFRS) in human beings, a severe systemic inflammatory disease with high mortality. It remains obscure how HTNV infection leads to disparate outcomes in distinct species. Here, we revealed a differential immune status in murine versus humans post HTNV infection, which was orchestrated by the macrophage reprogramming process and characterized by late-phase inactivation of NF-κB signaling. In HFRS patients, the immoderate and continuous activation of inflammatory monocyte/macrophage (M1) launched TNFα-centered cytokine storm and aggravated host immunopathologic injury, which can be life-threatening; however, in field or laboratory mice, the M1 activation and TNFα release were significantly suppressed at the late infection stage of HTNV, restricting excessive inflammation and b...

Integrative Analysis of HTNV Glycoprotein Derived MHC II Epitopes by In Silico Prediction and Experimental Validation

Frontiers in Cellular and Infection Microbiology, 2021

Hantaan virus (HTNV), the causative pathogen of hemorrhagic fever with renal syndrome (HFRS), is ... more Hantaan virus (HTNV), the causative pathogen of hemorrhagic fever with renal syndrome (HFRS), is a negative RNA virus belonging to the Orthohantaviridae family. HTNV envelope glycoprotein (GP), encoded by the genomic medium segment, is immunogenic and is therefore a promising vaccine candidate. Major histocompatibility complex class I (MHC-I) epitopes derived from HTNV has been extensively studied, but little is known of MHC-II epitopes. In silico predictions based on four databases indicated that the full-length HTNV GP has 1121 15-mer epitopes, of which 289 had a high score for binding to the human and murine MHC-II superfamily. It found that epitope ILTVLKFIANIFHTS could potentially bind most MHC-II molecules covering human and murine haplotypes. Dominant epitopes were validated by enzyme-linked immunospot assay of splenocytes from immunized mice; 6 of 10 epitopes supported the predictions including TATYSIVGPANAKVP, TKTLVIGQCIYTITS, FSLLPGVAHSIAVEL, CETYKELKAHGVSCP, CGLYLDRLKPVGS...

Wear-aware Memory Management Scheme for Balancing Lifetime and Performance of Multiple NVM Slots

2019 35th Symposium on Mass Storage Systems and Technologies (MSST), 2019

Emerging Non-Volatile Memory (NVM) has many advantages, such as near-DRAM speed, byte-addressabil... more Emerging Non-Volatile Memory (NVM) has many advantages, such as near-DRAM speed, byte-addressability, and persistence. Modern computer systems contain many memory slots, which are exposed as a unified storage interface by shared address space. Since NVM has limited write endurance, many wear-leveling techniques are implemented in hardware. However, existing hardware techniques can only effective in a single NVM slot, which cannot ensure wear-leveling among multiple NVM slots. This paper explores how to optimize a storage system with multiple NVM slots in terms of performance and lifetime. We show that simple integration of multiple NVMs in traditional memory policies results in poor reliability. We also reveal that existing hardware wear-leveling technologies are ineffective for a system with multiple NVM slots. In this paper, we propose a common wear-aware memory management scheme for in-memory file system. The proposed memory scheme enables wear-aware control of NVM slot use which minimizes the cost of performance and lifetime. We implemented the proposed memory management scheme and evaluated their effectiveness. The experiments show that the proposed wear-aware memory management scheme can outperform wear-leveling effect by more than 2600x, and the lifetime of NVM can be prolonged by 2.5x, the write performance can be improved by up to 15%.

[Isolation and purification of host factors interacting with Hantaan virus nucleocapsid protein]

Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, 2019

Objective To construct the plasmid expressing the fusion protein of Hantaan virus nucleocapsid pr... more Objective To construct the plasmid expressing the fusion protein of Hantaan virus nucleocapsid protein (HTNV NP) with affinity tag, and isolate the host factors interacting with NP using the affinity purification. Methods The synthetic streptavidin-FLAG (SF) gene and HTNV NP gene were cloned into the mammalian eukaryotic expression vector to obtain the recombinant expression plasmid (pCAGGS-SF-NP). The plasmid pCAGGS-SF-NP was transfected into HEK293T cells, and the expression of SF-NP was detected by Western blotting. Next, cell lysates were mixed with StrepTrapTM HP agar beads. After incubating overnight at 4DegreesCelsius, the agar beads were transferred into affinity chromatography column and washed with elution buffer. Finally, the binding proteins that interacted with SF-NP were collected by competitive elution buffer with desthiobiotin, and then were subjected to SDS-PAGE. Results The recombinant SF-NP proteins were highly expressed in eukaryotic cells. The host factors inter...

Unveiling the Mystery of Internet Packet Forwarding

ACM Computing Surveys, 2021

Validating the network paths taken by packets is critical in constructing a secure Internet archi... more Validating the network paths taken by packets is critical in constructing a secure Internet architecture. Any feasible solution must both enforce packet forwarding along end-host specified paths and verify whether packets have taken those paths. However, the current Internet supports neither enforcement nor verification. Likely due to the radical changes to the Internet architecture and a long-standing confusion between routing and forwarding, only limited solutions for path validation exist in the literature. This survey article aims to reinvigorate research on the essential topic of path validation by crystallizing not only how path validation works but also where seemingly qualified solutions fall short. The analyses explore future research directions in path validation aimed at improving security, privacy, and efficiency.

Research on Market Rating Quantification System Based on Markov Model and Vector Machine

2021 IEEE International Conference on Power, Intelligent Computing and Systems (ICPICS), 2021

Aiming at online marketing and selling products, this paper needs to identify the key patterns, r... more Aiming at online marketing and selling products, this paper needs to identify the key patterns, relationships, measures and parameters in the ratings and comments provided by customers related to other competitive products in the past, in order to provide information for their online sales strategies. and identify important design features that may improve product desirability. This paper first analyzes the three product data sets provided to identify, describe and support the relationships, measures and parameters among mathematical evidence, meaningful quantitative and / or qualitative models, star ratings, reviews and help ratings, and then, define a comprehensive product scoring standard, with star rating, review score and help score as three independent variables to measure the level of the product, in order to understand the real needs of customers. Finally, we need to establish the relationship between customers' subjective feelings and product scores, and then analyze what customers really like.

Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Frontiers in Microbiology, 2020

Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal... more Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviru...

Corrigendum: Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Frontiers in Microbiology, 2020

N6-methyladenosine modifications enhance enterovirus 71 ORF translation through METTL3 cytoplasmic distribution

Biochemical and Biophysical Research Communications, 2020

During replication, numerous viral RNAs are modified by N6-methyladenosine (m6A), the most abunda... more During replication, numerous viral RNAs are modified by N6-methyladenosine (m6A), the most abundant internal RNA modification. m6A is believed to regulate elements of RNA metabolism, such as splicing, stability, translation, secondary structure formation, and viral replication. In this study, we assessed the occurrence of m6A modification of the EV71 genome in human cells and revealed a preferred, conserved modification site across diverse viral strains. A single m6A modification at the 5' UTR-VP4 junction was shown to perform a protranslational function. Depletion of the METTL3 methyltransferase or treatment with 3-deazaadenosine significantly reduced EV71 replication. Specifically, METTL3 colocalized with the viral dsRNA replication intermediate in the cytoplasm during EV71 infection. As a nuclear resident protein, METTL3 relies on the binding of the nuclear import protein karyopherin to its nuclear localization signal (NLS) for nuclear translocation. We observed that EV71 2A and METTL3 share nuclear import proteins. The results of this study revealed an inner mechanism by which EV71 2A regulates the subcellular location of METTL3 to amplify its own gene expression, providing an increased understanding of RNA epitranscriptomics during the EV71 replication cycle.

Protective CD8+ T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epitope peptides in HLA-A2.1/Kb transgenic mice

Background An effective vaccine that prevents disease caused by hantaviruses is a global public h... more Background An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope....

Corrigendum: An Improved Enzyme-Linked Focus Formation Assay Revealed Baloxavir Acid as a Potential Antiviral Therapeutic Against Hantavirus Infection

Frontiers in Pharmacology, 2020

An Improved Enzyme-Linked Focus Formation Assay Revealed Baloxavir Acid as a Potential Antiviral Therapeutic Against Hantavirus Infection

Frontiers in Pharmacology, 2019

Hantaviruses, etiologic pathogens responsible for two severe human diseases, exist in areas rangi... more Hantaviruses, etiologic pathogens responsible for two severe human diseases, exist in areas ranging from Eurasia to America and remain global public health concerns. Conventionally, plaque formation assays have been used for hantavirus titering. However, hantaviruses replicate slowly within cells and produce minimal cytopathic effects, making this technique difficult to master. The improved enzyme-linked immunosorbent assaybased antigen detection method is easier to perform but is still time consuming. Here, we established an enzyme-linked focus formation assay (FFA) for Hantaan virus titering that is twice as fast as traditional assays. Moreover, using this method, we evaluated the effects of favipiravir (T-705) and another influenza virus drug, baloxavir acid (BXA), on hantavirus replication. We found that the endonuclease inhibitor BXA exerted similar anti-hantavirus effects as T-705. Overall, we developed a time-saving method for hantavirus titering and suggest BXA as a potential treatment choice for hantavirus-exposed individuals.

LiFePO4/(C+Cu) composite with excellent cycling stability as lithium ion battery cathodes synthesized via a modified carbothermal reduction method

Ceramics International, 2018

LiFePO 4 /(C+Cu) composite with excellent cycling stability as lithium ion battery cathodes synth... more

Identification of novel adefovir dipivoxil-saccharin cocrystal polymorphs and their thermodynamic polymorphic transformations

International Journal of Pharmaceutics, 2019

In this paper, two novel polymorphs of adefovir dipivoxil-saccharin (AD-SAC) cocrystals, forms II... more In this paper, two novel polymorphs of adefovir dipivoxil-saccharin (AD-SAC) cocrystals, forms II and III, were prepared and characterized by PXRD, DSC, FT-IR and SEM. Polymorphic transformations of these two forms and the known form (form I) were also investigated. In comparison to form I, forms II and III of AD-SAC cocrystals showed different thermal behaviors on DSC, characteristic diffraction peaks on PXRD and absorption spectra on FT-IR. In addition, form I exhibited an irregular plate-like shape, while forms II and III showed as needle-like shape and stubby columnar shape, respectively. During the heating process on DSC, forms I and II underwent solid-solid transformations to form III with endothermic transition peaks, suggesting that forms I and II were enantiotropically related to form III. Furthermore, slurry conversion experiments in ethanol showed forms II and III would quickly convert to form I by solution-mediated transformation, indicating that form I was the most stable form among three forms of AD-SAC cocrystal from 15 to 50 o C.

The Glycoprotein and Nucleocapsid Protein of Hantaviruses Manipulate Autophagy Flux to Restrain Host Innate Immune Responses

Cell Reports, 2019

Highlights d HTNV infection dynamically manipulates host autophagy flux for viral benefit d Gn-in... more Highlights d HTNV infection dynamically manipulates host autophagy flux for viral benefit d Gn-induced mitophagy facilitates MAVS degradation and delays host IFN responses d NP prevents autophagy-dependent clearance of Gn by binding to LC3B and SNAP29 d Inhibiting autophagy at the early infection stage can restrict HTNV replication

An algal lectin griffithsin inhibits Hantaan virus infection in vitro and in vivo

Frontiers in Cellular and Infection Microbiology

Hantaan virus (HTNV) is the etiological pathogen of hemorrhagic fever with renal syndrome in East... more Hantaan virus (HTNV) is the etiological pathogen of hemorrhagic fever with renal syndrome in East Asia. There are currently no effective therapeutics approved for HTNV and other hantavirus infections. We found that griffithsin (GRFT), an algae-derived lectin with broad-spectrum antiviral activity against various enveloped viruses, can inhibit the growth and spread of HTNV. In vitro experiments using recombinant vesicular stomatitis virus (rVSV) with HTNV glycoproteins as a model revealed that the GRFT inhibited the entry of rVSV-HTNV-G into host cells. In addition, we demonstrated that GRFT prevented authentic HTNV infection in vitro by binding to the viral N-glycans. In vivo experiments showed that GRFT partially protected the suckling mice from death induced by intracranial exposure to HTNV. These results demonstrated that GRFT can be a promising agent for inhibiting HTNV infection.

Dihydropyridine-derived calcium channel blocker as a promising anti-hantavirus entry inhibitor

Frontiers in Pharmacology

Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with ren... more Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are distributed from Eurasia to America. HFRS and HPS have mortality rates of up to 15% or 45%, respectively. Currently, no certified therapeutic has been licensed to treat hantavirus infection. In this study, we discovered that benidipine hydrochloride, a calcium channel blocker, inhibits the entry of hantaviruses in vitro. Moreover, an array of calcium channel inhibitors, such as cilnidipine, felodipine, amlodipine, manidipine, nicardipine, and nisoldipine, exhibit similar antiviral properties. Using pseudotyped vesicular stomatitis viruses harboring the different hantavirus glycoproteins, we demonstrate that benidipine hydrochloride inhibits the infection by both HFRS- and HPS-causing hantaviruses. The results of our study indicate the possibility of repurposing FDA-approved calcium channel blockers for the treatment of hanta...

A laboratory study on the dielectric spectroscopy of sandstone and the improvement of dispersion model

Journal of Petroleum Science and Engineering

LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

Frontiers in Microbiology

As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and is ... more As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and is the leading causative agent of severe hemorrhagic fever with renal syndrome (HFRS), which has profound morbidity and mortality. Macrophages are crucial components of the host innate immune system and serve as the first line of defense against HTNV infection. Previous studies indicated that the viral replication efficiency in macrophages determines hantavirus pathogenicity, but it remains unknown which factor manipulates the macrophage activation pattern and the virus-host interaction process. Here, we performed the transcriptomic analysis of HTNV-infected mouse bone marrow-derived macrophages and identified the long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1), especially the isoform NEAT1-2, as one of the lncRNAs that is differentially expressed at the early phase. Based on coculture experiments, we revealed that silencing NEAT1-2 hinders inflammatory macrophage...

[Establishment of an immortalized human umbilical vein endothelial cell line used for the study of the innate immune response to Hantaan virus]

Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, 2021

Objective To establish the immortalized human umbilical vein vascular endothelial cells (HUVECs-h... more Objective To establish the immortalized human umbilical vein vascular endothelial cells (HUVECs-hTERT) by introducing hTERT gene into primary HUVECs. In order to evaluate the potential of HUVECs-hTERT as a research model of HTNV infection, we explored the infection efficiency of Hantaan virus (HTNV) in HUVECs-hTERT and the influence of celluar innate immune regulation. Methods hTERT gene was cloned into lentivirus vector pCDH-CMV-MCS-EF1-puro, resulting in pCDH-CMV-hTERT-EF1-puro plasmid which was packaged into lentivirus. Then it was infected with HUVECs, and the HUVECs which stably express hTERT gene was selected by using puromycin and named HUVECs-hTERT. The morphology of HUVECs-hTERT and endothelial cell marker molecules, such as human von Willebrand factor (vWF), CD31 and vascular endothelial cell cadherin (VE-cadherin) were identified by microscopic observation and immunofluorescence assay. The percentage of nucleocapsid protein (NP)-positive cells after HTNV infection was det...

Differential Macrophage Phenotype Rewired by Hantaan Virus Constrains the Magnitude of Inflammatory Responses in Murine versus Humans

Hantaan virus (HTNV) is principally maintained and transmitted by rodents in nature, the infectio... more Hantaan virus (HTNV) is principally maintained and transmitted by rodents in nature, the infection of which is non-pathogenic in the field or laboratory mouse, but can cause hemorrhagic fever with renal syndrome (HFRS) in human beings, a severe systemic inflammatory disease with high mortality. It remains obscure how HTNV infection leads to disparate outcomes in distinct species. Here, we revealed a differential immune status in murine versus humans post HTNV infection, which was orchestrated by the macrophage reprogramming process and characterized by late-phase inactivation of NF-κB signaling. In HFRS patients, the immoderate and continuous activation of inflammatory monocyte/macrophage (M1) launched TNFα-centered cytokine storm and aggravated host immunopathologic injury, which can be life-threatening; however, in field or laboratory mice, the M1 activation and TNFα release were significantly suppressed at the late infection stage of HTNV, restricting excessive inflammation and b...

Integrative Analysis of HTNV Glycoprotein Derived MHC II Epitopes by In Silico Prediction and Experimental Validation

Frontiers in Cellular and Infection Microbiology, 2021

Hantaan virus (HTNV), the causative pathogen of hemorrhagic fever with renal syndrome (HFRS), is ... more Hantaan virus (HTNV), the causative pathogen of hemorrhagic fever with renal syndrome (HFRS), is a negative RNA virus belonging to the Orthohantaviridae family. HTNV envelope glycoprotein (GP), encoded by the genomic medium segment, is immunogenic and is therefore a promising vaccine candidate. Major histocompatibility complex class I (MHC-I) epitopes derived from HTNV has been extensively studied, but little is known of MHC-II epitopes. In silico predictions based on four databases indicated that the full-length HTNV GP has 1121 15-mer epitopes, of which 289 had a high score for binding to the human and murine MHC-II superfamily. It found that epitope ILTVLKFIANIFHTS could potentially bind most MHC-II molecules covering human and murine haplotypes. Dominant epitopes were validated by enzyme-linked immunospot assay of splenocytes from immunized mice; 6 of 10 epitopes supported the predictions including TATYSIVGPANAKVP, TKTLVIGQCIYTITS, FSLLPGVAHSIAVEL, CETYKELKAHGVSCP, CGLYLDRLKPVGS...

Wear-aware Memory Management Scheme for Balancing Lifetime and Performance of Multiple NVM Slots

2019 35th Symposium on Mass Storage Systems and Technologies (MSST), 2019

Emerging Non-Volatile Memory (NVM) has many advantages, such as near-DRAM speed, byte-addressabil... more Emerging Non-Volatile Memory (NVM) has many advantages, such as near-DRAM speed, byte-addressability, and persistence. Modern computer systems contain many memory slots, which are exposed as a unified storage interface by shared address space. Since NVM has limited write endurance, many wear-leveling techniques are implemented in hardware. However, existing hardware techniques can only effective in a single NVM slot, which cannot ensure wear-leveling among multiple NVM slots. This paper explores how to optimize a storage system with multiple NVM slots in terms of performance and lifetime. We show that simple integration of multiple NVMs in traditional memory policies results in poor reliability. We also reveal that existing hardware wear-leveling technologies are ineffective for a system with multiple NVM slots. In this paper, we propose a common wear-aware memory management scheme for in-memory file system. The proposed memory scheme enables wear-aware control of NVM slot use which minimizes the cost of performance and lifetime. We implemented the proposed memory management scheme and evaluated their effectiveness. The experiments show that the proposed wear-aware memory management scheme can outperform wear-leveling effect by more than 2600x, and the lifetime of NVM can be prolonged by 2.5x, the write performance can be improved by up to 15%.

[Isolation and purification of host factors interacting with Hantaan virus nucleocapsid protein]

Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, 2019

Objective To construct the plasmid expressing the fusion protein of Hantaan virus nucleocapsid pr... more Objective To construct the plasmid expressing the fusion protein of Hantaan virus nucleocapsid protein (HTNV NP) with affinity tag, and isolate the host factors interacting with NP using the affinity purification. Methods The synthetic streptavidin-FLAG (SF) gene and HTNV NP gene were cloned into the mammalian eukaryotic expression vector to obtain the recombinant expression plasmid (pCAGGS-SF-NP). The plasmid pCAGGS-SF-NP was transfected into HEK293T cells, and the expression of SF-NP was detected by Western blotting. Next, cell lysates were mixed with StrepTrapTM HP agar beads. After incubating overnight at 4DegreesCelsius, the agar beads were transferred into affinity chromatography column and washed with elution buffer. Finally, the binding proteins that interacted with SF-NP were collected by competitive elution buffer with desthiobiotin, and then were subjected to SDS-PAGE. Results The recombinant SF-NP proteins were highly expressed in eukaryotic cells. The host factors inter...

Unveiling the Mystery of Internet Packet Forwarding

ACM Computing Surveys, 2021

Validating the network paths taken by packets is critical in constructing a secure Internet archi... more Validating the network paths taken by packets is critical in constructing a secure Internet architecture. Any feasible solution must both enforce packet forwarding along end-host specified paths and verify whether packets have taken those paths. However, the current Internet supports neither enforcement nor verification. Likely due to the radical changes to the Internet architecture and a long-standing confusion between routing and forwarding, only limited solutions for path validation exist in the literature. This survey article aims to reinvigorate research on the essential topic of path validation by crystallizing not only how path validation works but also where seemingly qualified solutions fall short. The analyses explore future research directions in path validation aimed at improving security, privacy, and efficiency.

Research on Market Rating Quantification System Based on Markov Model and Vector Machine

2021 IEEE International Conference on Power, Intelligent Computing and Systems (ICPICS), 2021

Aiming at online marketing and selling products, this paper needs to identify the key patterns, r... more Aiming at online marketing and selling products, this paper needs to identify the key patterns, relationships, measures and parameters in the ratings and comments provided by customers related to other competitive products in the past, in order to provide information for their online sales strategies. and identify important design features that may improve product desirability. This paper first analyzes the three product data sets provided to identify, describe and support the relationships, measures and parameters among mathematical evidence, meaningful quantitative and / or qualitative models, star ratings, reviews and help ratings, and then, define a comprehensive product scoring standard, with star rating, review score and help score as three independent variables to measure the level of the product, in order to understand the real needs of customers. Finally, we need to establish the relationship between customers' subjective feelings and product scores, and then analyze what customers really like.

Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Frontiers in Microbiology, 2020

Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal... more Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviru...

Corrigendum: Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Frontiers in Microbiology, 2020

N6-methyladenosine modifications enhance enterovirus 71 ORF translation through METTL3 cytoplasmic distribution

Biochemical and Biophysical Research Communications, 2020

During replication, numerous viral RNAs are modified by N6-methyladenosine (m6A), the most abunda... more During replication, numerous viral RNAs are modified by N6-methyladenosine (m6A), the most abundant internal RNA modification. m6A is believed to regulate elements of RNA metabolism, such as splicing, stability, translation, secondary structure formation, and viral replication. In this study, we assessed the occurrence of m6A modification of the EV71 genome in human cells and revealed a preferred, conserved modification site across diverse viral strains. A single m6A modification at the 5' UTR-VP4 junction was shown to perform a protranslational function. Depletion of the METTL3 methyltransferase or treatment with 3-deazaadenosine significantly reduced EV71 replication. Specifically, METTL3 colocalized with the viral dsRNA replication intermediate in the cytoplasm during EV71 infection. As a nuclear resident protein, METTL3 relies on the binding of the nuclear import protein karyopherin to its nuclear localization signal (NLS) for nuclear translocation. We observed that EV71 2A and METTL3 share nuclear import proteins. The results of this study revealed an inner mechanism by which EV71 2A regulates the subcellular location of METTL3 to amplify its own gene expression, providing an increased understanding of RNA epitranscriptomics during the EV71 replication cycle.

Protective CD8+ T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epitope peptides in HLA-A2.1/Kb transgenic mice

Background An effective vaccine that prevents disease caused by hantaviruses is a global public h... more Background An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope....

Corrigendum: An Improved Enzyme-Linked Focus Formation Assay Revealed Baloxavir Acid as a Potential Antiviral Therapeutic Against Hantavirus Infection

Frontiers in Pharmacology, 2020

An Improved Enzyme-Linked Focus Formation Assay Revealed Baloxavir Acid as a Potential Antiviral Therapeutic Against Hantavirus Infection

Frontiers in Pharmacology, 2019

Hantaviruses, etiologic pathogens responsible for two severe human diseases, exist in areas rangi... more Hantaviruses, etiologic pathogens responsible for two severe human diseases, exist in areas ranging from Eurasia to America and remain global public health concerns. Conventionally, plaque formation assays have been used for hantavirus titering. However, hantaviruses replicate slowly within cells and produce minimal cytopathic effects, making this technique difficult to master. The improved enzyme-linked immunosorbent assaybased antigen detection method is easier to perform but is still time consuming. Here, we established an enzyme-linked focus formation assay (FFA) for Hantaan virus titering that is twice as fast as traditional assays. Moreover, using this method, we evaluated the effects of favipiravir (T-705) and another influenza virus drug, baloxavir acid (BXA), on hantavirus replication. We found that the endonuclease inhibitor BXA exerted similar anti-hantavirus effects as T-705. Overall, we developed a time-saving method for hantavirus titering and suggest BXA as a potential treatment choice for hantavirus-exposed individuals.

LiFePO4/(C+Cu) composite with excellent cycling stability as lithium ion battery cathodes synthesized via a modified carbothermal reduction method

Ceramics International, 2018

LiFePO 4 /(C+Cu) composite with excellent cycling stability as lithium ion battery cathodes synth... more

Identification of novel adefovir dipivoxil-saccharin cocrystal polymorphs and their thermodynamic polymorphic transformations

International Journal of Pharmaceutics, 2019

In this paper, two novel polymorphs of adefovir dipivoxil-saccharin (AD-SAC) cocrystals, forms II... more In this paper, two novel polymorphs of adefovir dipivoxil-saccharin (AD-SAC) cocrystals, forms II and III, were prepared and characterized by PXRD, DSC, FT-IR and SEM. Polymorphic transformations of these two forms and the known form (form I) were also investigated. In comparison to form I, forms II and III of AD-SAC cocrystals showed different thermal behaviors on DSC, characteristic diffraction peaks on PXRD and absorption spectra on FT-IR. In addition, form I exhibited an irregular plate-like shape, while forms II and III showed as needle-like shape and stubby columnar shape, respectively. During the heating process on DSC, forms I and II underwent solid-solid transformations to form III with endothermic transition peaks, suggesting that forms I and II were enantiotropically related to form III. Furthermore, slurry conversion experiments in ethanol showed forms II and III would quickly convert to form I by solution-mediated transformation, indicating that form I was the most stable form among three forms of AD-SAC cocrystal from 15 to 50 o C.

The Glycoprotein and Nucleocapsid Protein of Hantaviruses Manipulate Autophagy Flux to Restrain Host Innate Immune Responses

Cell Reports, 2019

Highlights d HTNV infection dynamically manipulates host autophagy flux for viral benefit d Gn-in... more Highlights d HTNV infection dynamically manipulates host autophagy flux for viral benefit d Gn-induced mitophagy facilitates MAVS degradation and delays host IFN responses d NP prevents autophagy-dependent clearance of Gn by binding to LC3B and SNAP29 d Inhibiting autophagy at the early infection stage can restrict HTNV replication