Publications by authors named "Yao Deng"

151 Publications

Urinary bisphenol A and its interaction with CYP17A1 rs743572 are associated with breast cancer risk.

Chemosphere 2021 Aug 12;286(Pt 3):131880. Epub 2021 Aug 12.

Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Objective: Bisphenol A (BPA), a common endocrine disrupter, can be activated by cytochrome P450 (CYP) metabolizing enzymes and might influence the development of breast cancer (BC). We hypothesized that BPA could interact with CYP genes, synergistically contributing to the BC risk.

Methods: Urinary BPA was measured in a total of 302 newly diagnosed BC patients and 302 healthy controls by ultra-high performance liquid chromatography-high resolution mass spectrometry. A set of seven CYP gene polymorphisms was genotyped by using the Sequenom MassARRAY system. A multivariate logistic regression model was used to assess the associations of BPA and BPA-SNP interaction with BC risk.

Results: BC patients had a higher urinary BPA concentration than healthy individuals (P < 0.001). Each 1-unit increase in log-transformed urinary BPA was associated with a 54 % increased BC risk [95 % confidence interval (CI), 1.34-1.77, P < 0.001]. Individuals with the CYP19A1 rs1902580 GA + AA genotype showed a significantly higher BC risk than those with the GG genotype (OR = 1.45, 95 % CI, 1.01-2.09, P < 0.05). A significant BPA-CYP17A1 rs743572 interaction was found to be associated with a higher risk of BC (P = 0.020). Compared with low-BPA individuals carrying CYP17A1 rs743572 GG genotypes, high-BPA individuals with the GA + AA genotype had a higher BC risk, with an odds ratio of 2.49 (95 % CI, 1.52-4.13, P < 0.05).

Conclusions: The positive association of BPA exposure with BC risk might be modified by CYP17A1 rs743572, providing evidence for the interaction effect of environment-genes on the etiology of BC.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131880DOI Listing
August 2021

Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma.

Allergol Int 2021 Jul 28. Epub 2021 Jul 28.

Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, China. Electronic address:

Background: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma.

Methods: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control.

Results: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment.

Conclusions: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.
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http://dx.doi.org/10.1016/j.alit.2021.07.004DOI Listing
July 2021

Abnormal somatosensory evoked potentials in a child with motor conversion disorder: A case report.

Psychiatry Clin Neurosci 2021 Jul 30. Epub 2021 Jul 30.

Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1111/pcn.13291DOI Listing
July 2021

SARS-CoV-2-specific T cell immunity to structural proteins in inactivated COVID-19 vaccine recipients.

Cell Mol Immunol 2021 08 15;18(8):2040-2041. Epub 2021 Jul 15.

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

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http://dx.doi.org/10.1038/s41423-021-00730-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280564PMC
August 2021

Profiles of SARS-CoV-2 RNA and Antibodies in Inpatients with COVID-19 not Related with Clinical Manifestation: A Single Centre Study.

Virol Sin 2021 Jul 1. Epub 2021 Jul 1.

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.

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http://dx.doi.org/10.1007/s12250-021-00411-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248291PMC
July 2021

Bisphenol A exposure, interaction with genetic variants and colorectal cancer via mediating oxidative stress biomarkers.

Environ Pollut 2021 Oct 23;287:117630. Epub 2021 Jun 23.

Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Bisphenol A (BPA) may induce oxidative stress as well as the toxicity of colon cancer cells. We hypothesized that BPA exposure and interactions with genetic variants might be associated with colorectal cancer (CRC) risk, and the association might be partly mediated by oxidative stress. We measured urinary BPA and three oxidative stress markers [8-iso-prostaglandinF (8-isoPGF), 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in 275 new CRC cases and 538 healthy controls. A set of 25 genetic variations in 12 candidate DNA repair genes and 5 metabolic enzyme genes were genotyped by Sequenom MassARRAY approach. In multivariable logistic regression, significant positive associations of CRC risk with BPA, 8-OHdG and HNE-MA were observed. Additionally, 8-OHdG, HNE-MA and 8-isoPGF were significantly positively associated with BPA (P < 0.05). The mediation analysis showed BPA-associated HNE-MA significantly mediated 11.81% of the effect of BPA on CRC risk. Moreover, BPA was found to interact with ERCC5 rs17655 and rs2296147 (both P < 0.05) to increase CRC risk. In brief, our results suggested BPA was associated with CRC risk and the positive association of BPA with CRC risk might be partly mediated by the oxidative stress HNE-MA. BPA might interact with ERCC5 rs17655 and rs2296147 to increase CRC risk.
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http://dx.doi.org/10.1016/j.envpol.2021.117630DOI Listing
October 2021

A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity.

Signal Transduct Target Ther 2021 05 31;6(1):213. Epub 2021 May 31.

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.
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http://dx.doi.org/10.1038/s41392-021-00634-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165147PMC
May 2021

Co-Immunization With CHIKV VLP and DNA Vaccines Induces a Promising Humoral Response in Mice.

Front Immunol 2021 24;12:655743. Epub 2021 Mar 24.

National Health Commission (NHC) Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.

Chikungunya fever is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV), for which no licensed vaccines are currently available. Here, we explored several immunization protocols and investigated their immunity and protective effects in mice, with DNA- and virus-like particle (VLP)- vaccines, both alone and in combination. Both DNA and VLP vaccine candidates were developed and characterized, which express CHIKV structural genes (C-E3-E2-6K-E1). Mice were immunized twice, with different protocols, followed by immunological detection and CHIKV Ross challenge. The highest antigen-specific IgG and neutralizing activity were induced by DNA and VLP co-immunization, while the highest cellular immunity was induced by DNA vaccination alone. Although all vaccine groups could protect mice from lethal CHIKV challenge, demonstrated as reduced viral load in various tissues, without weight loss, mice co-immunized with DNA and VLP exhibited the mildest histopathological changes and lowest International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) scores, in comparison to mice with either DNA or VLP vaccination alone. We concluded that co-immunization with DNA and VLP is a promising strategy to inducing better protective immunity against CHIKV infection.
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http://dx.doi.org/10.3389/fimmu.2021.655743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044884PMC
March 2021

Auxin-Mediated Regulation of Dorsal Vascular Cell Development May Be Responsible for Sucrose Phloem Unloading in Large Panicle Rice.

Front Plant Sci 2021 25;12:630997. Epub 2021 Feb 25.

College of Agriculture, Nanjing Agricultural University, Nanjing, China.

Large panicle rice cultivars often fail to fulfill their high-yield potential due to the poor grain filling of inferior spikelets (IS), which appears as initially stagnant development and low final seed weight. Understanding the mechanism of the initial stagnancy is important to improve IS grain filling. In this study, superior spikelets (SS) were removed from two homozygous japonica rice varieties (W1844 and CJ03) with the same sink capacity in an attempt to force photosynthate transport to the IS. The results showed that SS removal increased the grain weight, sucrose content, starch accumulation, and endogenous IAA levels of IS during the initial grain-filling stage. SS removal also improved the patterns of vascular cells in the dorsal pericarp and the expression levels of genes involved in sucrose transport ( and ) and IAA metabolism ( and ). Exogenous IAA application advanced the initiation of grain filling by increasing the sucrose content and the gene expression levels of sucrose transporters. These results indicate that auxin may act like a signal substance and play a vital role in initial grain filling by regulating dorsal vascular cell development and sucrose phloem unloading into caryopsis.
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http://dx.doi.org/10.3389/fpls.2021.630997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947352PMC
February 2021

Distinct roles of PI3Kδ and PI3Kγ in a toluene diisocyanate-induced murine asthma model.

Toxicology 2021 04 9;454:152747. Epub 2021 Mar 9.

Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

TDI-induced asthma is characterized by neutrophil-dominated airway inflammation and often associated with poor responsiveness to steroid treatment. Both PI3Kδ and PI3Kγ have been demonstrated to play important proinflammatory roles in ovalbumin-induced asthma. We've already reported that blocking pan PI3K effectively attenuated TDI-induced allergic airway inflammation. Yet the specific functions of PI3Kδ and PI3Kγ in TDI-induced asthma are still unclear. Male BALB/c mice were first dermally sensitized and then challenged with TDI to generate an asthma model. Sellective inhibitors of PI3Kδ (IC-87114, AMG319) and PI3Kγ (AS252424, AS605240) were respectively given to the mice after each airway challenge. Treatment with IC-87114 or AMG319 after TDI exposure led to significantly decreased airway hyperresponsiveness (AHR), less neutrophil and eosinophil accumulation, attenuated airway smooth muscle (ASM) thickening, less M1 and M2 macrophages in lung, as well as lower levels of IL-4, IL-5, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) and recovered IL-10 production. While mice treated with AS252424 or AS605240 had increased AHR, more severe ASM thickening, larger numbers of neutrophils and eosinophils, more M1 but less M2 macrophages, and higher BALF levels of IL-4, IL-5, IL-6, IL-10, IL-12, IL-18 when compared with those treated with vehicle. These data revealed that pharmacological inhibition of PI3Kδ attenuates TDI-induced airway inflammation while PI3Kγ inhibition exacerbates TDI-induced asthma, indicating distinct biological functions of PI3Kδ and PI3Kγ in TDI-induced asthma.
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http://dx.doi.org/10.1016/j.tox.2021.152747DOI Listing
April 2021

Anti-DLL4 ameliorates toluene diisocyanate-induced experimental asthma by inhibiting Th17 response.

Int Immunopharmacol 2021 May 9;94:107444. Epub 2021 Feb 9.

The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510260, China. Electronic address:

Toluene diisocyanate (TDI) exhibits an ability to induce steroid insensitive asthma with the involvement of Th17 cells. And emerging evidence has indicated that DLL4 signaling promotes Th17 differentiation through directly upregulating Rorc and IL-17 transcription. Thus, we sought to evaluate the effects of DLL4 blocking antibody on TDI-induced asthma model. Female BALB/c mice were sensitized and challenged with TDI to generate an asthma model. TDI-exposed mice were intraperitoneally injected with anti-DLL4 antibody and then analyzed for various parameters of the airway inflammatory responses. Increased expression of DLL4 in spleen and lung was detected in TDI-exposed mice. Furthermore, anti-DLL4 treatment alleviated TDI-induced airway hyperreactivity (AHR), airway inflammation, airway epithelial injury and airway smooth muscle (ASM) thickening. In the meantime, neutralizing DLL4 also blunted Th17 response via downregulation of ROR-γt expression, while had no effect on Th2 cells and regulatory T (Treg) cells. Overall, anti-DLL4 ameliorated TDI-induced experimental asthma by inhibiting Th17 response, implying the feasibility of targeting DLL4 for therapy of Th17-predominant severe asthma.
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http://dx.doi.org/10.1016/j.intimp.2021.107444DOI Listing
May 2021

Decreased Vascular Bundle 1 affects mitochondrial and plant development in rice.

Rice (N Y) 2021 Jan 25;14(1):13. Epub 2021 Jan 25.

Rice Research Institute, Key Laboratory of Application and Safety Control of Genetically Modified Crops, College of Agronomy and Biotechnology, Academy of Agricultural Sciences, Southwest University, Chongqing, 400715, China.

Background: Mitochondria are vital regulators of plant growth and development, constitute the predominant source of ATP, and participate in multiple anabolic and catabolic metabolic pathways. But the mechanism by which dysfunctional mitochondria affect plant growth remains unknown, and more mitochondria-defective mutants need to be identified.

Results: A mitochondria-defective mutant decreased vascular bundle 1 (dvb1) was isolated from rice mutant library mutagenized by EMS (ethylmethane sulfonate), which shows dwarfism, narrow leaves, short branches, few vascular bundles, and low fertility. Map-based cloning, genetic complementation, and phylogenetic analysis revealed that DVB1 encodes a structural protein classified in the Mic10 family and is required for the formation of cristae in mitochondria, and was primarily expressed in vascular bundles. The DVB1 protein is partially localized in the mitochondria and capable of forming dimers and polymers. Comparing with the wild type, disruption of amino acid metabolism and increased auxin synthesis were observed in dvb1 mutant which also showed increased sensitivity to the mitochondrial electron transport inhibitors.

Conclusions: DVB1 belongs to Mic10 family and DVB1 is partially localized in the mitochondria. Further studies indicated that DVB1 is important for mitochondrial and plant development in rice.
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http://dx.doi.org/10.1186/s12284-021-00454-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835275PMC
January 2021

Molecular Epidemiology and Risk Factors of sp. Infections Among General Populations in Yunnan Province, Southwestern China.

Risk Manag Healthc Policy 2020 29;13:1791-1801. Epub 2020 Sep 29.

Key Laboratory of National Health Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, Jiangsu Province, People's Republic of China.

Background: is a common enteric parasite of controversial pathogenic roles in human diseases. Although the prevalence of infections has been investigated in a diverse range of populations, there is little knowledge on the molecular epidemiology and risk factors of infections among general populations in southeastern China.

Materials And Methods: A total of 507 individuals were randomly selected in Yunnan province, China from July 2016 to March 2017. Stool specimens were sampled for detection of sp. using PCR assay, and the risk factors of infections were identified. isolates were subtyped, and the associations of infections and subtypes with clinical manifestations were examined.

Results: The overall detection rate of sp. was 9.47% (95% : 7.13-12.44%). Toilet type ( = 3.248, 95% CI: 1.245-8.473), anemia ( = 2.601, 95% : 1.245-8.473) and type of daily drinking water ( = 3.11, 95% : 1.557-6.213) were identified as risk factors of infections; however, infections showed no associations with clinical symptoms. Four subtypes (ST1 to ST4) were characterized in isolates, in which ST3 was predominant (4.73%, 95% : 3.2-6.94%), followed by ST1 (3.16%, 95% : 1.95-5.07%), ST4 (1.38%, 95% : 0.07-2.82%) and ST2 (0.2%, 95% : 0-1.11%). In addition, ST1 subtype infection was found to correlate with anemia ( = 4.66, 95% : 1.631-14.314).

Conclusions: There is a high prevalence of infections among general populations in Yunnan province, southwestern China, and toilet type, anemia and type of daily drinking water are risk factors of infections. ST3 is the dominant subtype of sp. characterized, and ST1 correlates with anemia. Improving hygiene conditions, developing healthy lifestyles and intensifying health education programs are strongly recommended to reduce the prevalence and transmission potential of infections.
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http://dx.doi.org/10.2147/RMHP.S269664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532910PMC
September 2020

CancerImmunityQTL: a database to systematically evaluate the impact of genetic variants on immune infiltration in human cancer.

Nucleic Acids Res 2021 01;49(D1):D1065-D1073

Department of Epidemiology and Biostatistics, Key Laboratory of Environmental Health of Ministry of Education, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Tumor-infiltrating immune cells as integral component of the tumor microenvironment are associated with tumor progress, prognosis and responses to immunotherapy. Genetic variants have been demonstrated to impact tumor-infiltrating, underscoring the heritable character of immune landscape. Therefore, identification of immunity quantitative trait loci (immunQTLs), which evaluate the effect of genetic variants on immune cells infiltration, might present a critical step toward fully understanding the contribution of genetic variants in tumor development. Although emerging studies have demonstrated the determinants of germline variants on immune infiltration, no database has yet been developed to systematically analyze immunQTLs across multiple cancer types. Using genotype data from TCGA database and immune cell fractions estimated by CIBERSORT, we developed a computational pipeline to identify immunQTLs in 33 cancer types. A total of 913 immunQTLs across different cancer types were identified. Among them, 5 immunQTLs are associated with patient overall survival. Furthermore, by integrating immunQTLs with GWAS data, we identified 527 immunQTLs overlapping with known GWAS linkage disequilibrium regions. Finally, we constructed a user-friendly database, CancerImmunityQTL (http://www.cancerimmunityqtl-hust.com/) for users to browse, search and download data of interest. This database provides an informative resource to understand the germline determinants of immune infiltration in human cancer and benefit from personalized cancer immunotherapy.
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http://dx.doi.org/10.1093/nar/gkaa805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778991PMC
January 2021

Correction: Ciclopirox activates PERK-dependent endoplasmic reticulum stress to drive cell death in colorectal cancer.

Cell Death Dis 2020 Sep 3;11(9):719. Epub 2020 Sep 3.

Protein Quality Control and Diseases laboratory, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41419-020-02868-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471902PMC
September 2020

NS1-based DNA vaccination confers mouse protective immunity against ZIKV challenge.

Infect Genet Evol 2020 11 1;85:104521. Epub 2020 Sep 1.

Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Medical Virology, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China; NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China. Electronic address:

The recent pandemic of Zika virus (ZIKV) infections highlight the urgent need for the development of a safe and efficacious ZIKV vaccine. We previously demonstrated that robust humoral and cellular immunity was elicited in BALB/c mice by ZIKV DNA vaccine encoding the precursor membrane (prM) and envelope (E) proteins while the protective efficacies were not evaluated against ZIKV challenge. To further explore the protective immunity elicited by various targets of ZIKV, we constructed a novel DNA-based vaccine expressing nonstructural protein 1 (NS1), named as VRC-NS1, and evaluated and compared immune responses and protective efficacies of three ZIKV DNA vaccine candidates (VRC-prME, VRC-NS1, and VRC-prME+VRC-NS1) using an A129 (Ifnar) murine challenge model. The results showed that each of DNA vaccine candidates induced robust antigen-specific humoral immunity and conferred protection against ZIKV-SMGC-1 with two doses (20 μg per dose) of homologous intramuscularly (i.m.) immunizations via in vivo electroporation. All DNA vaccine candidates induced significant protection against infection-associated weight loss in addition to preventing viral replication in blood, brain and spleen tissue following in vivo viral challenge. Notably, NS1-based DNA vaccination alone was capable of conferring mouse protective immunity to reduce viremia and viral burden in tissues against ZIKV challenge, even though it did not induce neutralizing antibodies. These data demonstrated that VRC-NS1 and VRC-prME are highly promising vaccine candidates for ZIKV control. Furthermore, our results highlight an alternative strategy (DNA vaccine based on non-neutralizing antigen NS1) for designing novel flaviviral vaccines (including for ZIKV) and provide a foundation for the development of a safe and effective NS1-based vaccine against ZIKV infection.
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http://dx.doi.org/10.1016/j.meegid.2020.104521DOI Listing
November 2020

Development and effectiveness of pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test .

Biosaf Health 2020 Dec 21;2(4):226-231. Epub 2020 Aug 21.

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

With the development of the COVID-19 epidemic, there is an urgent need to establish a system for determining the effectiveness and neutralizing activity of vaccine candidates in biosafety level 2 (BSL-2) facilities. Previously, researchers had developed a pseudotyped virus system for SARS-CoV and MERS-CoV, based on HIV-1 core, bearing virus spike protein. During the development of a pseudotyped SARS-CoV-2 system, a eukaryotic expression plasmid expressing SARS-CoV-2 spike (S) protein was constructed and then co-transfected with HIV-1 based plasmid which containing the firefly luciferase reporter gene, into HEK293T cells to prepare the pseudotyped SARS-CoV-2 virus (ppSARS-2). We have successfully established the pseudotyped SARS-CoV-2 system for neutralization and entry inhibition assays. Huh7.5 cell line was found to be the most susceptible to our pseudotyped virus model. Different levels of neutralizing antibodies were detected in convalescent serum samples of COVID-19 patients using ppSARS-2. The recombinant, soluble, angiotensin-converting enzyme 2 protein was found to inhibit the entry of ppSARS-2 in Huh7.5 cells effectively. Furthermore, the neutralization results for ppSARS-2 were consistent with those of live SARS-CoV-2 and determined using the serum samples from convalescent patients. In conclusion, we have developed an easily accessible and reliable tool for studying the neutralizing efficiency of antibodies against SARS-CoV-2 and the entry process of the virus in a BSL-2 laboratory.
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http://dx.doi.org/10.1016/j.bsheal.2020.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442068PMC
December 2020

Pyridoxine induces monocyte-macrophages death as specific treatment of acute myeloid leukemia.

Cancer Lett 2020 11 26;492:96-105. Epub 2020 Aug 26.

The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, 510260, PR China. Electronic address:

Acute myeloid leukemia (AML) is an aggressive hematological malignancy that gradually develops resistance to current chemotherapy treatments. The available chemotherapy drugs show serious non-specific cytotoxicity to healthy normal cells, resulting in relapse and low survival rates. Natural small molecules with less toxicity and high selectivity for AML are urgently needed. In this study, we confirmed that pyridoxine (vitamin B6) selectively induces monocyte macrophages to undergo programmed cell death in two different modes: caspase-3-dependent apoptosis in U937 cells or GSDME-mediated pyroptosis in THP-1 cells. Further molecular analysis indicated that blocking the caspase pathway could switch the death to MLKL-dependent necroptosis and subsequent extensive inflammatory response. Pyridoxine also delayed the disease progression in a THP-1 leukemia mouse model. In addition, it induced the death of primary AML cells from AML patients by activating caspase-8/3. Overall, our results identify pyridoxine, a low-toxicity natural small molecule, as a potential therapeutic drug for AML treatment.
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http://dx.doi.org/10.1016/j.canlet.2020.08.018DOI Listing
November 2020

Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells.

Nat Commun 2020 08 6;11(1):3910. Epub 2020 Aug 6.

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 102206, Beijing, China.

SARS-CoV-2, a β-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.
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http://dx.doi.org/10.1038/s41467-020-17796-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413383PMC
August 2020

Ciclopirox activates PERK-dependent endoplasmic reticulum stress to drive cell death in colorectal cancer.

Cell Death Dis 2020 07 27;11(7):582. Epub 2020 Jul 27.

Protein Quality Control and Diseases laboratory, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

Ciclopirox (CPX) modulates multiple cellular pathways involved in the growth of a variety of tumor cell types. However, the effects of CPX on colorectal cancer (CRC) and the underlying mechanisms for its antitumor activity remain unclear. Herein, we report that CPX exhibited strong antitumorigenic properties in CRC by inducing cell cycle arrest, repressing cell migration, and invasion by affecting N-cadherin, Snail, E-cadherin, MMP-2, and MMP-9 expression, and disruption of cellular bioenergetics contributed to CPX-associated inhibition of cell growth, migration, and invasion. Interestingly, CPX-induced reactive oxygen species (ROS) production and impaired mitochondrial respiration, whereas the capacity of glycolysis was increased. CPX (20 mg/kg, intraperitoneally) substantially inhibited CRC xenograft growth in vivo. Mechanistic studies revealed that the antitumor activity of CPX relies on apoptosis induced by ROS-mediated endoplasmic reticulum (ER) stress in both 5-FU-sensitive and -resistant CRC cells. Our data reveal a novel mechanism for CPX through the disruption of cellular bioenergetics and activating protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent ER stress to drive cell death and overcome drug resistance in CRC, indicating that CPX could potentially be a novel chemotherapeutic for the treatment of CRC.
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http://dx.doi.org/10.1038/s41419-020-02779-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385140PMC
July 2020

Lack of antibody-mediated cross-protection between SARS-CoV-2 and SARS-CoV infections.

EBioMedicine 2020 Aug 21;58:102890. Epub 2020 Jul 21.

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China. Electronic address:

Background: The novel coronavirus (SARS-CoV-2) shares approximately 80% whole genome sequence identity and 66% spike (S) protein identity with that of SARS-CoV. The cross-neutralization between these viruses is currently not well-defined.

Methods: Here, by using the live SARS-CoV-2 virus infection assay as well as HIV-1 based pseudotyped-virus carrying the spike (S) gene of the SARS-CoV-2 (ppSARS-2) and SARS-CoV (ppSARS), we examined whether infections with SARS-CoV and SARS-CoV-2 can induce cross-neutralizing antibodies.

Findings: We confirmed that SARS-CoV-2 infects cells via angiotensin converting enzyme 2 (ACE2), the functional receptor for SARS-CoV, and we also found that the recombinant receptor binding domain (RBD) of the S protein of SARS-CoV effectively inhibits ppSARS-2 entry in Huh7.5 cells. However, convalescent sera from SARS-CoV and SARS-CoV-2 patients showed high neutralizing activity only against the homologous virus, with no or limited cross-neutralization activity against the other pseudotyped virus. Similar results were also observed in vaccination studies in mice.

Interpretation: Our study demonstrates that although both SARS-CoV and SARS-CoV-2 use ACE2 as a cellular receptor, the neutralization epitopes are not shared by these two closely-related viruses, highlighting challenges towards developing a universal vaccine against SARS-CoV related viruses.

Funding: This work was supported by the National Key Research and Development Program of China, the National Major Project for Control and Prevention of Infectious Disease in China, and the One Belt and One Road Major Project for infectious diseases.
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http://dx.doi.org/10.1016/j.ebiom.2020.102890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372296PMC
August 2020

Integration of platelet features in blood and platelet rich plasma for detection of lung cancer.

Clin Chim Acta 2020 Oct 4;509:43-51. Epub 2020 Jun 4.

Department of clinical laboratory, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China; Center for Informational Biology, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. Electronic address:

Objectives: To determine whether the integration platelet features in blood and platelet rich plasma can establish a model to diagnose lung cancer and colon cancer, even differentiate lung malignancy from lung benign diseases.

Methods: 245 individuals including 159 lung cancer and 86 normal participants were divided into the training cohort and testing cohort randomly. Then, 32 colon cancers, 37 lung cancers, and 21 benign patients were enrolled into validate cohort. The whole blood and corresponding platelet rich plasma (PRP) samples from all participants were prospectively collected, and the platelet features were determined. The features which are statistically significant at the univariate analysis in the training cohort and reported significant features were entered the diagnostic model. A receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy of the model in each cohort.

Results: In the training cohort, multiple platelet features were significantly different in lung cancer patients, including MPV in whole blood, MPV, and platelet count in PRP and platelet recovery rate (PRR). For the training cohort, the diagnostic model for lung cancer performed well (AUC = 0.92). The probability distribution of lung cancers and controls in testing cohort were also separated well by the diagnostic model (AUC = 0.79). The diagnostic model for colon cancer also performed well (AUC = 0.79). The model also has a potential value in differentiating the lung malignancy from the benign (AUC = 0.69).

Conclusion: The PRR was first raised and used in the detection of lung cancer. This study identified a diagnostic model based on PRR and other platelet features in whole blood and PRP samples with the potential to distinguish patients with lung cancer or colon cancer from healthy controls. The model could also be used to distinguish between lung cancer from the benign disease.
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http://dx.doi.org/10.1016/j.cca.2020.05.043DOI Listing
October 2020

A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect MERS-CoV specific IgG in humans and animals.

Biosaf Health 2019 Dec 20;1(3):134-143. Epub 2019 Dec 20.

MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.

The Middle East respiratory syndrome (MERS) is a lethal zoonosis caused by MERS coronavirus (MERS-CoV) and poses a significant threat to public health worldwide. Therefore, a rapid, sensitive, and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness. Here, we evaluated various novel luciferase immunosorbent assays (LISA) based on nucleocapsid protein (NP) as well as fragments derived from spike protein (S) including subunit 1 (S1), N terminal domain (NTD), receptor-binding domain (RBD) and subunit 2 (S2) of S for the detection of MERS-CoV-specific IgG. Fusion proteins, including nanoluciferase (NLuc) and various fragments derived from the NP or S protein of MERS-CoV, were expressed in human embryonic kidney 293 T cells. LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins. Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR, commercial S1-based ELISA, and pseudovirus particle neutralization test (ppNT). Our results showed that the S1-, RBD-, and NP-LISAs were more sensitive than the NTD- and S2-LISAs for the detection of anti-MERS-CoV IgG. Furthermore, the S1-, RBD-, and NP-LISAs were more sensitive (by at least 16-fold) than the commercially available S1-ELISA. Moreover, the S1-, RBD-, and NP-LISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV (OC43, 229E, HKU1, NL63)-infected patients. More importantly, these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels, monkeys, and mice, among which the RBD-LISA exhibited excellent performance. The results of this study suggest that the novel MERS-CoV RBD- and S1- LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples. These assays have the potential to be used as serologic tests for the management and control of MERS-CoV infection.
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http://dx.doi.org/10.1016/j.bsheal.2019.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148641PMC
December 2019

Two nights of recovery sleep restores hippocampal connectivity but not episodic memory after total sleep deprivation.

Sci Rep 2020 05 29;10(1):8774. Epub 2020 May 29.

Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.

Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal connectivity to multiple prefrontal and default mode network regions, and disrupted the relationships between memory performance and hippocampal connectivity. Following TSD, two nights of recovery sleep restored hippocampal connectivity to baseline levels, but did not fully restore memory performance nor its associations with hippocampal connectivity. These findings suggest that more than two nights of recovery sleep are needed to fully restore memory function and hippocampal-memory associations after one night of total sleep loss.
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http://dx.doi.org/10.1038/s41598-020-65086-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260173PMC
May 2020

Toll-like Receptor 4 Deficiency Aggravates Airway Hyperresponsiveness and Inflammation by Impairing Neutrophil Apoptosis in a Toluene Diisocyanate-Induced Murine Asthma Model.

Allergy Asthma Immunol Res 2020 Jul;12(4):608-625

The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation.

Methods: TLR4 and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4 mice after each challenge.

Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4 mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4 mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis.

Conclusions: These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.
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http://dx.doi.org/10.4168/aair.2020.12.4.608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225000PMC
July 2020

Geographic variation in maternal investment and trade-offs between egg size and clutch size in an endemic toad of the Qinghai-Tibet Plateau.

Sci Rep 2020 04 22;10(1):6838. Epub 2020 Apr 22.

Department of Biology, College of Life Science, Xinyang Normal University, Xinyang, SD, 464000, China.

Life history theory predicts that animals often produce fewer offspring of larger size and indicate a stronger trade-off between the number and size of offspring to cope with increasing environmental stress. In order to evaluate this prediction, we tested the life history characteristics of Bufo minshanicus at eight different altitudes on the eastern Tibetan Plateau, China. Our results revealed a positive correlation between female SVL and clutch size or egg size, revealing that larger females produce more and larger eggs. However, high-altitude toads seem to favor more offspring and smaller egg sizes when removing the effect of female SVL, which is counter to theoretical predictions. In addition, there was an overall significantly negative relationship between egg size and clutch size, indicative of a trade-off between egg size and fecundity. Therefore, we suggest that higher fecundity, rather than larger egg size, is a more effective reproductive strategy for this species of anuran living at high-altitude environments.
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http://dx.doi.org/10.1038/s41598-020-63635-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176715PMC
April 2020

CpG-methylation-based risk score predicts progression in colorectal cancer.

Epigenomics 2020 04 17;12(7):605-615. Epub 2020 Mar 17.

Department of Epidemiology & Biostatistics & Ministry of Education Key Lab of Environment & Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, PR China.

To identify patients with colorectal cancer (CRC) who are at a truly higher risk of progression, which is key for individualized approaches to precision therapy. We developed a predictor associated with progression-free interval (PFI) using The Cancer Genome Atlas CRC methylation data. The risk score was associated with PFI in the whole cohort (p < 0.001). A nomogram consisting of the risk score and other significant clinical features was generated to predict the 3- and 5-year PFI in the whole set (area under the curve: 0.79 and 0.71, respectively). The risk score based on 23 DNA-methylation sites may serve as the basis for improved prediction of progression in patients with CRC in future clinical practice.
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http://dx.doi.org/10.2217/epi-2019-0300DOI Listing
April 2020

Automated Determination of Dissolved Reactive Phosphorus at Nanomolar to Micromolar Levels in Natural Waters Using a Portable Flow Analyzer.

Anal Chem 2020 03 25;92(6):4379-4386. Epub 2020 Feb 25.

State Key Laboratory of Marine Environmental Science, Fujian Provincial Key Laboratory for Coastal Ecology and Environmental Studies, Dongshan Swire Marine Station, College of the Environment and Ecology, Xiamen University, Xiamen 361102, People's Republic of China.

Automated in-field methods for measuring dissolved reactive phosphorus (DRP) over a large concentration range are in high demand for the purpose of better understanding the biogeochemistry of phosphorus in the river-estuary-coast continuum to the open ocean. Here, an automated portable and robust analyzer was described for the determination of nanomolar to micromolar levels of DRP in natural waters. The quantification of DRP was based on classic phosphomolybdenum blue (PMB) chemistry. All the components of the analyzer were computer-controlled using LabVIEW-based laboratory-programmed software. When equipped with a 3 cm Z-type flow cell, the system demonstrated linearity with concentrations up to 12 μmol L, a sampling rate of 20 h, a limit of detection of 0.11 μmol L, and relative standard deviations (RSDs) of 0.4-4.6% ( = 11-576). When a solid-phase extraction cartridge was combined with the analyzer, the PMB formed from the sample was automatically concentrated on the hydrophilic-lipophilic balanced sorbent. The concentrated PMB compound was eluted with NaOH solution and measured in the spectrophotometric system. Under optimal conditions, the nanomolar-level mode afforded a sampling rate of 8 h, a limit of detection of 1.7 nmol L, and RSDs of 3.0-5.7% ( = 11-120). The system exhibited advantages that included a wide linear range, high sensitivity and reproducibility, low reagent consumption, and insignificant interference from salinity, silicate, arsenate, and other P-containing compounds. The system was successfully applied for discrete sample analysis, fixed site online monitoring, and the real-time underway measurement of DRP in riverine-estuarine-coastal waters.
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http://dx.doi.org/10.1021/acs.analchem.9b05252DOI Listing
March 2020

Notoginsenoside R1 suppresses miR-301a via NF-κB pathway in lipopolysaccharide-treated ATDC5 cells.

Exp Mol Pathol 2020 02 11;112:104355. Epub 2019 Dec 11.

Department of Rheumatology and Immunology, Shengli Oilfield Central Hospital, Dongying 257034, China. Electronic address:

Background: Notoginsenoside R1 (NG-R1) exhibits a pharmacological activity against excessive inflammation. Here, we aimed to ascertain the anti-inflammatory role of NG-R1 in ankylosing spondylitis (AS) as well as the possible mechanism which is still under to be elucidated.

Methods: In this study, lipopolysaccharide (LPS) was applied to evoke extreme inflammation in ATDC5 cells. To investigate the anti-inflammatory property of NG-R1, ATDC5 cells were exposed to NG-R1 prior to LPS stimulation. microRNA-301a (miR-301a)-overexpressed ATDC5 cells were established which confirmed by qRT-PCR. Then, inflammatory lesions were indicated by cell viability, apoptosis and inflammatory factors, including interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α). Nuclear factor-kappa B (NF-κB) pathway was determined by Western blotting assay.

Results: We found NG-R1 dramatically dampened the decrease of cell viability, facilitation of apoptosis and abundance of inflammatory factors induced by LPS. Additionally, NG-R1 pre-incubation impeded LPS-induced accumulation of miR-301a. However, the protective capacity of NG-R1 was impaired by miR-301a overexpression. Of note, LPS-caused phosphorylation of p65 and inhibitor of nuclear factor kappa-B alpha (IκBα) was repressed by NG-R1, while further enhanced in miR-301-transfected ATDC5 cells.

Conclusion: NG-R1 relived LPS-elicited inflammatory damages via blocking NF-κB in a miR-301a-silenced manner.
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http://dx.doi.org/10.1016/j.yexmp.2019.104355DOI Listing
February 2020

Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice.

Antiviral Res 2020 01 6;173:104646. Epub 2019 Nov 6.

Key Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China; Center for Biosafety Mega-Science, Chinese Academy of Sciences, China. Electronic address:

Human coronaviruses (HCoVs) are important pathogens that cause upper respiratory tract infections and have neuroinvasive abilities; however, little is known about the dynamic infection process of CoVs in vivo, and there are currently no specific antiviral drugs to prevent or treat HCoV infection. Here, we verified the replication ability and pathogenicity of a reporter HCoV-OC43 strain expressing Renilla luciferase (Rluc; rOC43-ns2DelRluc) in mice with different genetic backgrounds (C57BL/6 and BALB/c). Additionally, we monitored the spatial and temporal progression of HCoV-OC43 through the central nervous system (CNS) of live BALB/c mice after intranasal or intracerebral inoculation with rOC43-ns2DelRluc. We found that rOC43-ns2DelRluc was fatal to suckling mice after intranasal inoculation, and that viral titers and Rluc expression were detected in the brains and spinal cords of mice infected with rOC43-ns2DelRluc. Moreover, viral replication was initially observed in the brain by non-invasive bioluminescence imaging before the infection spread to the spinal cord of BALB/c mice, consistent with its tropism in the CNS. Furthermore, the Rluc readout correlated with the HCoV replication ability and protein expression, which allowed quantification of antiviral activity in live mice. Additionally, we validated that chloroquine strongly inhibited rOC43-ns2DelRluc replication in vivo. These results provide new insights into the temporal and spatial dissemination of HCoV-OC43 in the CNS, and our methods provide an extremely sensitive platform for evaluating the efficacy of antiviral therapies to treat neuroinvasive HCoVs in live mice.
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http://dx.doi.org/10.1016/j.antiviral.2019.104646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114176PMC
January 2020
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