Publications by authors named "Jinlong Cheng"

30 Publications

  • Page 1 of 1

The furin-S2' site in avian coronavirus plays a key role in central nervous system damage progression.

J Virol 2021 Mar 16. Epub 2021 Mar 16.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China

The furin cleavage site plays an important role in virus pathogenicity. The spike protein of SARS-CoV-2 harbors a furin cleavage site insertion in contrast to SARS-CoV, which may be related to its stronger communicability. An avian coronavirus with an extra furin cleavage site upstream of the fusion peptide (S2' site) infected monocyte cells and neuron cells leading to viremia or encephalitis, respectively. Immunohistochemistry and real-time quantitative polymerase chain reaction were used to follow disease progression and demonstrated differences between the parent avian coronavirus and mutated avian coronavirus with a furin-S2' site. Magnetic resonance imaging and biological dye to evaluate the blood-brain barrier permeability showed that avian coronavirus with a furin-S2' site had increased permeability compared with parent avian coronavirus. Immunohistochemistry of brains after intracerebral injection of avian coronavirus and immunofluorescence staining of primary neuron cells demonstrated the furin-S2' site expanded the cell tropism of the mutant avian coronavirus to neuron cells. TNF-α, which has a key role in blood-brain barrier permeability, was highly induced by avian coronavirus with a furin-S2' site compared with the parent avian coronavirus. We demonstrated the process involved in mutant avian coronavirus-induced disease and that the addition of a furin-S2' site changed the virus cell tropism.Coronaviruses have broken out three times in two decades. Spike (S) protein plays a key role in the process of infection. To clarify importance of furin cleavage site in spike protein for coronavirus, we investigated the pathogenesis of neurotropic avian coronavirus whose spike protein contains an extra furin cleavage site (furin-S2' site). By combining real-time quantitative polymerase chain reaction and immunohistochemistry we demonstrated that infectious bronchitis virus (IBV) infects brain instead of trachea when its S protein contains furin-S2' site. Moreover, the virus was shown to increase the permeability of blood-brain barrier, infect neuron cells and induce high expression of TNF-α. Based on these results we further show that furin cleavage site in S protein plays an important role in coronavirus pathogenicity and cell tropism. Our study extends previous publications on function of S protein of coronavirus, increasing the understanding of researchers to coronavirus.
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http://dx.doi.org/10.1128/JVI.02447-20DOI Listing
March 2021

Fermented Soybean Meal Affects the Reproductive Performance and Oxidative Status of Sows, and the Growth of Piglets.

Animals (Basel) 2021 Feb 24;11(3). Epub 2021 Feb 24.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai 200240, China.

This study aimed to investigate the effect of the fermented soybean meal on the reproductive performance, oxidative stress and colostrum composition of sows, and the growth performance of their progeny. A total of 44 sows were allotted to four dietary groups ( = 11/group). The dietary groups included the basal diet group (control) and the treatment groups in which soybean meal in the basal diet was replaced with 2%, 4%, and 6% fermented soybean meal, respectively. The experimental diets were fed to the sows from the 78th day of gestation to the 21st day of lactation. Replacing soybean meal in the basal maternal diet with the fermented soybean meal decreased the levels of malondialdehyde, cortisol, and 8-iso-prostaglandinF2α in the serum of sows and increased the average weight of piglets on the 14th day and the 21st day after birth. The activity of superoxide dismutase in the serum of sows was increased in the group with 4% fermented soybean meal on the 17th day of lactation. The levels of estrogen and growth factors in the serum of sows were enhanced in the group with 6% fermented soybean meal. In the colostrum, the levels of the protein and the immunoglobulin G were enhanced in the group with 4% fermented soybean meal. In conclusion, replacing the soybean meal in the basal maternal diet with the fermented soybean meal attenuates the oxidative stress status of the gestational and lactational sows, and enhances the average weight of their offspring.
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http://dx.doi.org/10.3390/ani11030597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996358PMC
February 2021

An attenuated TW-like infectious bronchitis virus strain has potential to become a candidate vaccine and S gene is responsible for its attenuation.

Vet Microbiol 2021 Mar 17;254:109014. Epub 2021 Feb 17.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

TW-like infectious bronchitis virus (IBV) with high pathogenicity is becoming the predominant IBV type circulating in China. To develop vaccines against TW-like IBV strains and investigate the critical genes associated with their virulence, GD strain was attenuated by 140 serial passages in specific-pathogen-free embryonated eggs and the safety and efficacy of the attenuated GD strain (aGD) were examined. The genome sequences of GD and aGD were also compared and the effects of mutations in the S gene were observed. The results revealed that aGD strain showed no obvious pathogenicity with superior protective efficacy against TW-like and QX-like virulent IBV strains. The genomes of strains aGD and GD shared high similarity (99.87 %) and most of the mutations occurred in S gene. Recombinant IBV strain rGD, in which the S gene was replaced with the corresponding regions from aGD, showed decreased pathogenicity compared with its parental strain. In conclusion, attenuated TW-like IBV strain aGD is a potential vaccine candidate and the S gene is responsible for its attenuation. Our research has laid the foundation for future exploration of the attenuating molecular mechanism of IBV.
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http://dx.doi.org/10.1016/j.vetmic.2021.109014DOI Listing
March 2021

Coronavirus Endoribonuclease Ensures Efficient Viral Replication and Prevents Protein Kinase R Activation.

J Virol 2020 Dec 23. Epub 2020 Dec 23.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Coronavirus (CoV) nsp15 is an endoribonuclease conserved throughout the CoV family. The enzymatic activity and crystal structure of infectious bronchitis virus (IBV) nsp15 are undefined, and the protein's role in replication remains unclear. We verified the uridylate-specific endoribonuclease (EndoU) activity of IBV and found that the EndoU active sites were located in the C-terminus of nsp15 and included His223, His238, Lys278 and Tyr334. We further constructed an infectious clone of the IBV-rSD strain (rSD-wild-type [WT]) and EndoU-deficient IBVs by changing the codon for the EndoU catalytic residues to alanine. Both the rSD-WT and EndoU-deficient viruses propagated efficiently in embryonated chicken eggs. Conversely, EndoU-deficient viral propagation was severely impaired in chicken embryonic kidney cells, which was reflected in the lower viral mRNA accumulation and protein synthesis. After infecting chickens with the parental rSD-WT strain and EndoU-deficient viruses, the EndoU-deficient-virus-infected chickens presented reduced mortality, tissue injury and viral shedding. Coronaviruses can emerge from animal reservoirs into naive host species to cause pandemic respiratory and gastrointestinal diseases with significant mortality in humans and domestic animals. Infectious bronchitis virus (IBV), a γ-coronavirus, infects respiratory, renal and reproductive systems, causing millions of dollars in lost revenue worldwide annually. Mutating the viral endoribonuclease resulted in an attenuated virus and prevented protein kinase R activation. Therefore, EndoU activity is a virulence factor in IBV infections, thus providing an approach for generating live-attenuated vaccine candidates for emerging coronaviruses.
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http://dx.doi.org/10.1128/JVI.02103-20DOI Listing
December 2020

Safety, Immunogenicity, and Effectiveness of Defective Viral Particles Arising in Mast Cells Against Influenza in Mice.

Front Immunol 2020 13;11:585254. Epub 2020 Nov 13.

Key Laboratory of Animal Epidemiology of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Mast cells play pivotal roles in the pathogenesis of influenza A virus (IAV) infections. Defective viral particles (DPs) often arise during IAV replication, which can interfere with the replication of infectious viruses and stimulate the antiviral response of host cells. Therefore, DPs are expected to have immune-protective functions in clinic. However, the potent immunogenicity and effectiveness of DPs arising in mast cells during IAV replication have not been reported. In the present study, we showed that DPs generated in the human mastocytoma cell line HMC-1 following H1N1 infection were safe to mice after vaccination. Compared with lung adenocarcinoma cells, A549, DPs generated in infected mast cells had much better immunostimulatory activity, enhancing both humoral and cellular immunity of hosts. Notably, they could significantly increase the expression of immune-associated cytokines, especially the IFN-γ. Due to the robust immunogenicity, thus DPs generated in infected mast cells could stimulate the robust protective immune reaction effectively to fight against lethal IAV re-challenge after vaccination, which result in the high survival, decreased lung injury as well as inhibition of viral replication and inflammatory response in lungs. This study is the first to illustrate and explore the safety, immunogenicity, and effectiveness of DPs arising in mast cells against influenza as favorable potential vaccination. The results provide insight into the advances of new prophylactic strategies to fight influenza by focusing on DPs generated in mast cells.
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http://dx.doi.org/10.3389/fimmu.2020.585254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693459PMC
November 2020

Defective Viral Particles Produced in Mast Cells Can Effectively Fight Against Lethal Influenza A Virus.

Front Microbiol 2020 4;11:553274. Epub 2020 Nov 4.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Mast cells play an important role in the pathogenesis of highly pathogenic H5N1 avian influenza virus (H5N1-HPAIV) infection. Defective viral particles (DPs) can interfere with the replication of infectious viruses and stimulate the innate immune response of host cells. However, DPs arising from mast cells during HPAIV replication and their potent antiviral actions has not been reported. Here, we showed that the human mastocytoma cell line, HMC-1, allowed for the productive replication of the H5N1-HPAIV. Compared with alveolar cell line A549, DPs were propagated preferentially and abundantly in mast cells following IAV infection, which can be attributed to the wide existence of Argonaute 2 (AGO2) in HMC-1 cells. In addition, DPs generated in H5N1-infected cells could provide great therapeutic protection on mice to fight against various influenza A viruses, which included not only homologous H5N1-HPAIV, but also heterologous H1N1, H3N2, H7N2, and H9N2. Importantly, DPs generated in H5N1-infected HMC-1 cells could diminish viral virulence and by triggering a robust antiviral response through type II interferon signaling pathways. This study is the first to illustrate the arising of DPs in H5N1-HPAIV infected mast cells and explore their favorable ability to protect mice from influenza A viruses infection, which provides a novel insight and valuable information for the progress of new strategies to fight influenza A viruses infection, especially highly pathogenic avian influenza virus infection by focusing on the DPs generated in mast cells.
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http://dx.doi.org/10.3389/fmicb.2020.553274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671969PMC
November 2020

Oat bran and wheat bran impact net energy by shaping microbial communities and fermentation products in pigs fed diets with or without xylanase.

J Anim Sci Biotechnol 2020 8;11:99. Epub 2020 Oct 8.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193 China.

Background: Dietary fiber can be fermented in gut of pigs and the end products of fermentation were short-chain fatty acids (SCFA). The SCFA had positive effects on gut bacteria and host immune system. In addition, SCFA can provide a part of available energy for pigs. However, there were limited reports on the relationship between dietary fiber, gut bacteria, and energy metabolism. Therefore, this study investigated how dietary fiber and enzyme addition impacted energy metabolism by acting on the microbial community and SCFA.

Methods: Wheat bran (WB) was added to the corn-soybean meal-based diet at the levels of 12% and 27%, and oat bran (OB) at 15% and 36%. One of each diet was supplemented with or without 5000 U/kg feed of xylanase, so a total of 10 diets were allotted to 60 growing pigs (initial body weight: 27.2 ± 1.2 kg) using a randomized complete block design. The experiment was conducted in 10 consecutive periods using 6 similar open-circuit respiration chambers. Each pig was used for one 20-day period. During each period, six pigs were allowed 14 d to adapt to the diets in metabolic cages followed by 6 d (from d 15 to d 20) in respiration chambers to measure heat production (HP).

Results: Pigs fed 36% OB diets had greater ( <  0.05) nutrient digestibility and net energy (NE) values compared to those fed 27% WB diets. Apparent digestibility coefficients of dry matter (DM) and crude protein (CP) were lower ( < 0.05) in pigs fed 27% WB diets compared with those fed 12% WB diets. Enzyme addition improved ( < 0.05) the NE values (11.37 vs. 12.43 MJ/kg DM) in diets with 27% WB. Supplementation of xylanase did not affect NE values for basal diets, OB diets and 12%WB diets. Compared with diets with 36% OB, pigs fed 27% WB-based diets excreted more total SCFA, acetate and propionate (expressed as g/kg feed DM) in fecal samples of pigs ( < 0.05). Pigs in the WB diets had greater proportion of phylum Bacteroidetes while phylum Firmicutes were greater in pigs fed OB diets ( < 0.05). Pigs fed WB diets had greater ( < 0.05) abundance of Succinivibrio and which were associated with fiber degradation and SCFA production.

Conclusion: Our results indicated diets supplied by high level of OB or WB promote the growth of fiber-degrading bacteria. The differences in fiber composition between WB and OB led to differences in nutrient digestibility and bacterial communities, which were ultimately reflected in energy metabolism. Enzyme supplementation improved nutrient digestibility as well as NE values for 27% WB diets but not for other diets, which indicated that effects of enzyme were related to type and level of dietary fiber in diets.
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http://dx.doi.org/10.1186/s40104-020-00505-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542896PMC
October 2020

Replicase 1a gene plays a critical role in pathogenesis of avian coronavirus infectious bronchitis virus.

Virology 2020 11 20;550:1-7. Epub 2020 Aug 20.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. Electronic address:

Avian coronavirus infectious bronchitis virus (IBV) is an important pathogen threatening poultry production worldwide. Here, two recombinant IBVs (rYN-1a-aYN and rYN-1b-aYN) were generated in which ORF1a or ORF1b of the virulent YN genome were replaced by the corresponding regions from the attenuated strain aYN. The pathogenicity and virulence of rIBVs were evaluated in ovo and in vivo. The results revealed that mutations in the ORF1a gene during passage in embryonated eggs caused the decreased pathogenicity of virulent IBV YN strain, proven by determination of virus replication in ECEs and CEK cells, the observation of clinical signs, gross lesions, microscopic lesions, tracheal ciliary activity and virus distribution in chickens following exposure to rIBVs. However, mutations in ORF1b had no obvious effect on virus replication in both ECEs and CEK cells, or pathogenicity in chickens. Our findings demonstrate that the replicase 1a gene of avian coronavirus IBV is a determinant of pathogenicity.
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http://dx.doi.org/10.1016/j.virol.2020.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440038PMC
November 2020

Pathogenic characteristics of a QX-like infectious bronchitis virus strain SD in chickens exposed at different ages and protective efficacy of combining live homologous and heterologous vaccination.

Vet Res 2020 Jul 8;51(1):86. Epub 2020 Jul 8.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian, Beijing, 100193, China.

Continued reports of infections with infectious bronchitis virus (IBV) variants have occurred since its first isolation in the 1930s. Currently, QX-like IBVs are the predominant circulating genotype around the world. Here, the pathogenicity of QX-like IBV strain SD was characterized in chickens at different ages of exposure to the virus, and the protection efficacy of available vaccine combinations against IBV was evaluated. The results revealed that QX-like IBV strain SD was severely pathogenic in chickens, causing respiratory, urinary and reproductive infections, irrespective of age, based on clinical observations, viral distribution in tissues and a ciliostasis study. Severe respiratory signs, tracheal cilia injury, nephritis and abnormal development of the oviduct and ovarian follicles were evident throughout the experiment. A challenge experiment demonstrated that the homologous QX vaccine showed superior protection efficacy compared with other available vaccines, confirming the importance of IBV vaccine seed homology against the circulating IBV strains. Our findings aid an understanding of the pathogenicity of QX-like IBVs that may help to further control the infection.
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http://dx.doi.org/10.1186/s13567-020-00811-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341716PMC
July 2020

Pathogenicity and genome changes in QX-like infectious bronchitis virus during continuous passaging in embryonated chicken eggs.

Virus Res 2020 05 3;281:197911. Epub 2020 Mar 3.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People's Republic of China. Electronic address:

Infectious bronchitis (IB) remains a major problem in the global poultry industry despite the many available vaccines. Live attenuated vaccines are the most effective means of preventing IB and are traditionally generated by serial passaging of a wild strain in embryonated chicken eggs. In this study, the SZ isolate of the QX-like infectious bronchitis virus (IBV) was continuously passaged in chicken embryos for 250 passages. We compared the pathogenicity of different passages (SZ50, SZ100, SZ150, SZ200 and SZ250) of strain SZ by clinical signs, gross lesions, viral load, tissue tropism, weight gain and tracheal ciliary activity. As the passaging increased in the chicken embryos, the strain lost its ability to infect many organs, and the viral pathogenicity gradually decreased. We also found 23 genomic variations of the QX-like strain SZ throughout the passaging process by further analyzing its complete genome sequence. This work offers valuable insight for IBV vaccine development and further research on the IBV attenuation mechanisms.
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http://dx.doi.org/10.1016/j.virusres.2020.197911DOI Listing
May 2020

Characterization of emergent Avibacterium paragallinarum strains and the protection conferred by infectious coryza vaccines against them in China.

Poult Sci 2019 Dec;98(12):6463-6471

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Infectious coryza (IC), an acute respiratory disease of chickens, is caused by Avibacterium paragallinarum. Here, the current epidemiological status of IC was investigated in China over 5 yr (2013 to 2018). A total of 28 Av. paragallinarum field isolates were identified by PCR tests and by sequence analysis of the hemagglutinin gene. The pathogenicities of 4 field isolates, the efficacy of 2 commercial inactivated oil-emulsion IC vaccines and vaccines containing different Av. paragallinarum isolates were also evaluated. The PCRs revealed a high rate (51.5%) of sample positivity for Av. paragallinarum during 2013 to 2018. Phylogenetic analysis showed that most field strains fell into the same cluster and had a farther genetic relationship with the early isolates from China. Pathogenicity testing revealed that the Chinese Av. paragallinarum isolates were able to induce the typical clinical signs of IC; hence, they were clearly pathogenic to chickens. Vaccine efficacy tests revealed that the 2 commercial inactivated oil-emulsion IC vaccines we tested had low protection rates against 2 selected Av. paragallinarum isolates after a single immunization, whereas the inactivated vaccine containing the Av. paragallinarum BJ26 isolate generated a relatively high protection rate against the field isolates compared with other three tested vaccines. The results indicate that IC is currently prevalent in China, and that commercial vaccines have not counteracted its presence in this country.
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http://dx.doi.org/10.3382/ps/pez531DOI Listing
December 2019

The S2 Subunit of QX-type Infectious Bronchitis Coronavirus Spike Protein Is an Essential Determinant of Neurotropism.

Viruses 2019 10 22;11(10). Epub 2019 Oct 22.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Some coronaviruses (CoVs) have an extra furin cleavage site (RRKR/S, furin-S2' site) upstream of the fusion peptide in the spike protein, which plays roles in virion adsorption and fusion. Mutation of the S2' site of QX genotype (QX-type) infectious bronchitis virus (IBV) spike protein (S) in a recombinant virus background results in higher pathogenicity, pronounced neural symptoms and neurotropism when compared with conditions in wild-type IBV (WT-IBV) infected chickens. In this study, we present evidence suggesting that recombinant IBV with a mutant S2' site (furin-S2' site) leads to higher mortality. Infection with mutant IBV induces severe encephalitis and breaks the blood-brain barrier. The results of a neutralization test and immunoprotection experiment show that an original serum and vaccine can still provide effective protection in vivo and in vitro. This is the first demonstration of IBV-induced neural symptoms in chickens with encephalitis and the furin-S2' site as a determinant of neurotropism.
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http://dx.doi.org/10.3390/v11100972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832359PMC
October 2019

Successful establishment of a reverse genetic system for QX-type infectious bronchitis virus and technical improvement of the rescue procedure.

Virus Res 2019 10 17;272:197726. Epub 2019 Aug 17.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. Electronic address:

In this study, a pathogenic avian infectious bronchitis virus (IBV) QX-type strain YN was successfully rescued by vaccinia virus based reverse genetic technology. Ten fragments contiguously spanning the complete IBV genome were amplified and cloned into the vaccinia virus genome by homologous recombination. The full-length genomic cDNA was transcribed in vitro, and its transcript was transfected into BHK-21/N cells that could stably express IBV N protein. At 48 h post transfection, the culture medium was harvested and inoculated into 10-day-old specific-pathogen-free embryonated chicken eggs to replicate the rescued virus. This strategy was chosen to facilitate the rescue procedure and to ensure that the recombinant rYN virus will not require any cell culture adaptations. After only one in ovo passage, the recombinant YN virus (rYN) was successfully recovered and confirmed to possess the introduced silent marker mutation in its genome. Biological characteristics of rYN such as the EID, TCID, replication in ovo, and replication kinetcs in vitro were tested and all were similar to its parental strain YN. Our findings demonstrate the successful construction of highly-pathogenic QX-type IBV using a modified rescue procedure, allowing for future studies of the molecular biology and pathogenicity of IBV field strains.
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http://dx.doi.org/10.1016/j.virusres.2019.197726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114641PMC
October 2019

Pathogenicity of a GI-22 genotype infectious bronchitis virus isolated in China and protection against it afforded by GI-19 vaccine.

Virus Res 2019 07 10;267:59-66. Epub 2019 May 10.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

Avian infectious bronchitis (IB) is a globally circulating bird disease caused by infectious bronchitis virus (IBV). In China, the most prevalent IBV genotype is GI-19/QX-like because the protective efficiency of the classical IBV vaccine is low, and new GI-19 vaccines are under development. In 2018, a GI-22 genotype strain CK/CH/LGD/2018 (abbreviated 'LGD') was isolated in northern China, which caused 10%-30% morality in H120-vaccinated chickens. A phylogenetic analysis showed that this new isolate displays novel features compared with other earlier-isolated reference strains. To monitor the epidemic trend of IBV in China, the pathogenicity of LGD was first evaluated in 1-day-old specific-pathogen-free chickens. LGD induced classical IBV damage in the trachea and kidney, whereas it also infected and damaged the bursa of Fabricius, an important immune organ of chickens. The efficacy of our earlier-developed GI-19 vaccine, strain SZ200, against LGD was also evaluated in this study. The GI-19 genotype vaccine provided sufficient protection against the new GI-22 genotype strain, and may be a promising candidate vaccine with which to control both wild GI-19 and GI-22 strains in the future.
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http://dx.doi.org/10.1016/j.virusres.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172295PMC
July 2019

S gene and 5a accessory gene are responsible for the attenuation of virulent infectious bronchitis coronavirus.

Virology 2019 07 1;533:12-20. Epub 2019 May 1.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. Electronic address:

To explore the critical genes associated with infectious bronchitis virus (IBV) virulence, we compared the genome sequences of virulent YN strain and its attenuated strain aYN. Accumulation of mutations in the S gene and the accessory gene 5a were observed, suggesting a potential role in the loss of viral pathogenicity. Two recombinant IBVs (rIBVs) with replacement of the S gene or 5a with corresponding regions from aYN were rescued to verify this speculation. Embryo mortality time/rate showed that rYN-S-aYN and rYN-5a-aYN had an attenuated phenotype in ovo. Replication assay in ovo and in vitro demonstrated the rIBVs had similar replication patterns with wild-type rIBV. Both rIBVs showed reduced mortality, tissue lesions and tissue virus titers in chicken. In conclusion, S gene and 5a accessory gene are responsible for the attenuation of virulent IBV. Insight into the genes responsible for virus attenuation will facilitate the development of future vaccines against IBV.
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http://dx.doi.org/10.1016/j.virol.2019.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112010PMC
July 2019

Hemagglutinin-Neuraminidase and fusion genes are determinants of NDV thermostability.

Vet Microbiol 2019 Jan 19;228:53-60. Epub 2018 Nov 19.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. Electronic address:

Newcastle disease (ND) caused by infections with virulent strains of Newcastle disease virus (NDV) continues to be a threat for poultry industry worldwide. The prospect of developing a thermostable and effective NDV vaccine is still highly desirable. To investigate the determinants of thermostability in NDV, we generated recombinant NDV strains by exchanging viral hemagglutinin-neuraminidase (HN) gene or by mutating the fusion (F) gene. The results showed that the HN and F protein were both determinants of NDV thermostability. With increased thermostability, the HN protein-chimeric virus showed significantly reduced neuraminidase and hemadsorption activities, but its hemolytic activity was retained. We also found that changing the amino acid in the F protein cleavage sites, affected the thermostability as well as the pathogenicity and fusogenic capacity of the virus. Taken together, our results suggest that HN and F proteins both contribute to the thermostability of NDV, and other viral biological activities change as the thermostability of the virus changes. These findings should be of benefit to the development of a thermostable and efficacious NDV vaccine.
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http://dx.doi.org/10.1016/j.vetmic.2018.11.013DOI Listing
January 2019

Pathogenicity differences between a newly emerged TW-like strain and a prevalent QX-like strain of infectious bronchitis virus.

Vet Microbiol 2018 Dec 24;227:20-28. Epub 2018 Oct 24.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

TW-like IBV isolates have appeared frequently in recent years in mainland China. In this study, we compared the TW-like IBV GD strain and the predominant QX-like SD strain in terms of serology and pathogenicity to 3-week-old specific-pathogen-free chickens. Both strains could cause severe respiratory distress and renal lesions, with a mortality rate were approximately 20%. Virus were continuously shed via the respiratory tract and cloaca. However, the infection pattern of the two isolates were different. The GD strain persisted for a longer duration and caused extensive damages to the tracheas and lungs. Moreover, chickens infected with the GD strain showed inefficient recovery of damaged cilia after infection. Our findings suggested that the newly emerged TW-like IBV GD strain showed obvious differences in pathogenicity, tissue tropism and replication efficiency compared with the QX-like IBV SD strain, with the TW-like GD strain showing stronger tropism to the respiratory tract and a longer duration of clinical signs.
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http://dx.doi.org/10.1016/j.vetmic.2018.10.019DOI Listing
December 2018

Attenuation, safety, and efficacy of a QX-like infectious bronchitis virus serotype vaccine.

Vaccine 2018 03 26;36(14):1880-1886. Epub 2018 Feb 26.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address:

Avian infectious bronchitis (IB) is a highly contagious disease caused by avian infectious bronchitis virus (IBV), which is a considerable economic threat to the poultry industry. QX-like IBV strains have increasingly emerged in China in recent years. Hence, development of a specific vaccine to guard against their potential threat is important. In this study, we sought to develop an attenuated vaccine strain. First, attenuated QX-like IBV strain SZ130 was created by continuous passage in chicken embryos for 130 generations, and then its safety was tested. We also evaluated the protective efficacy of different doses of SZ130 against challenge with QX-like IBV field strain SD in chickens. SZ130-infected birds did not experience IB-like signs and organ lesions. Additionally, an excellent protective effect of SZ130 vaccination was observed when vaccinated birds were challenged with SD, with no clinical signs or gross lesions, decreased target tissue replication rates, and lower ciliostasis scores in all immunized groups. These findings indicate that attenuated IBV strain SZ130 is highly safe in chicks and may serve as an effective vaccine against the threat posed by QX-like IBV strains.
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http://dx.doi.org/10.1016/j.vaccine.2018.02.053DOI Listing
March 2018

Pathogenicity differences between QX-like and Mass-type infectious bronchitis viruses.

Vet Microbiol 2018 Jan 21;213:129-135. Epub 2017 Nov 21.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address:

Infectious bronchitis is a highly contagious, acute viral respiratory disease of chickens, caused by infectious bronchitis virus (IBV). In recent years, the isolation rate of QX-like IBV has increased in the world. To clarify this phenomenon and better understand the pathogenicity of QX-like IBV, we examined differences in pathogenicity between two IBV strains, SD and M41, which belong to QX-like and Mass-type IBV, respectively. SD strain was more virulent in 3-week-old specific-pathogen-free chickens than M41 strain causing higher mortality with severe renal lesions. The tissue distribution of the two virus strains was tested by real-time RT-PCR. The results showed that the viral genome copy numbers in the tissues of chickens inoculated with SD strain were higher than those in chickens inoculated with M41 strain, with the exception of the trachea and lung. This study indicates that there are tremendous differences in pathogenicity and tissue tropism between the QX-like strain and Mass-type strain. These findings may benefit the prevention of infectious bronchitis in the poultry industry in China.
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http://dx.doi.org/10.1016/j.vetmic.2017.11.027DOI Listing
January 2018

The glutamic residue at position 402 in the C-terminus of Newcastle disease virus nucleoprotein is critical for the virus.

Sci Rep 2017 12 12;7(1):17471. Epub 2017 Dec 12.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.

The nucleocapsid proteins (NPs) of Newcastle disease virus (NDV) and other paramyxoviruses play an important functional role during genomic RNA replication. Our previous study showed that the NP-encoding gene significantly influenced viral replication. Here, we investigated the roles of certain amino acid residues in the NP C-terminus in viral replication and virulence. Results showed that the glutamic acid residue at position 402 (E402) in the C-terminus of the NP is critical for RNA synthesis in the NDV mini-genome system. Mutation of E402 resulted in larger viral plaques that appeared more quickly, and increased the virulence of NDV. Further study indicated that the mutant virus had increased RNA levels during the early stages of virus infection, but that RNA replication was inhibited at later time points. These findings increase our knowledge of viral replication and contribute to a more comprehensive understanding of the virulence factors associated with NDV.
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http://dx.doi.org/10.1038/s41598-017-17803-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727133PMC
December 2017

Agreement Between Magnetic Resonance Imaging and Pathologic Findings in the Tumor Size Evaluation Before and After Neoadjuvant Chemotherapy Treatment: A Prospective Study.

Int J Gynecol Cancer 2017 09;27(7):1472-1479

*Department of Gynecology Oncology, The Affiliated Tumor Hospital of Harbin Medical University; †Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University; ‡Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education; §Harbin Medical University; and ∥Basic Medicine School, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.

Objectives: To compare the agreement between magnetic resonance imaging (MRI) results and postsurgical pathologic findings for tumor size evaluation in cervical cancer patients before and after neoadjuvant chemotherapy (NACT) treatment.

Methods: The study analyzed the agreement between pretreatment MRI results and postsurgical pathologic findings about the tumor size in 100 cervical cancer patients without NACT and 397 cervical cancer patients with NACT, respectively.

Results: In general, the agreement between pretreatment MRI results and postsurgical pathologic findings of tumor size was 0.855 (95% confidence interval [CI], 0.763-0.909) in cervical cancer patients without NACT, whereas the agreement between posttreatment MRI results and postsurgical pathologic findings was 0.503 (95% CI, 0.421-0.576). Only 62.72% (249/397) of patients who underwent NACT treatment have the same chemotherapy response evaluation results; the κ coefficient was 0.384(95% CI, 0.310-0.457) between posttreatment MRI and postsurgical pathologic findings. We still found International Federation of Gynecology and Obstetrics stage is associated with the chemotherapy response evaluation.

Conclusions: Our data suggest that pretreatment MRI can be a surrogate indicator for postsurgical pathologic findings. However, posttreatment MRI could not be a surrogate indicator for postsurgical pathologic findings. The chemotherapy response evaluation based on only MRI is not so reliable. More indicators should be developed for chemotherapy response evaluation.
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http://dx.doi.org/10.1097/IGC.0000000000001038DOI Listing
September 2017

Metabolic profiling and novel plasma biomarkers for predicting survival in epithelial ovarian cancer.

Oncotarget 2017 May;8(19):32134-32146

Department of Gynecology Oncology, the Tumor Hospital, Harbin Medical University, Harbin 150086, China.

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies around the world, and patients with ovarian cancer always have an extremely poor chance of survival. Therefore, it is meaningful to develop a highly efficient model that can predict the overall survival for EOC. In order to investigate whether metabolites could be used to predict the survival of EOC, we performed a metabolic analysis of 98 plasma samples with follow-up information, based on the ultra-performance liquid chromatography mass spectrometry (UPLC/MS) systems in both positive (ESI+) and negative (ESI-) modes. Four metabolites: Kynurenine, Acetylcarnitine, PC (42:11), and LPE(22:0/0:0) were selected as potential predictive biomarkers. The AUC value of metabolite-based risk score, together with pathological stages in predicting three-year survival rate was 0.80. The discrimination performance of these four biomarkers between short-term mortality and long-term survival was excellent, with an AUC value of 0.82. In conclusion, our plasma metabolomics study presented the dysregulated metabolism related to the survival of EOC, and plasma metabolites could be utilized to predict the overall survival and discriminate the short-term mortality and long-term survival for EOC patients. These results could provide supplementary information for further study about EOC survival mechanism and guiding the appropriate clinical treatment.
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http://dx.doi.org/10.18632/oncotarget.16739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458273PMC
May 2017

A Comprehensive Analysis of Metabolomics and Transcriptomics in Cervical Cancer.

Sci Rep 2017 02 22;7:43353. Epub 2017 Feb 22.

Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, 150086, P.R. China.

Cervical cancer (CC) still remains a common and deadly malignancy among females in developing countries. More accurate and reliable diagnostic methods/biomarkers should be discovered. In this study, we performed a comprehensive analysis of metabolomics (285 samples) and transcriptomics (52 samples) on the potential diagnostic implication and metabolic characteristic description in cervical cancer. Sixty-two metabolites were different between CC and normal controls (NOR), in which 5 metabolites (bilirubin, LysoPC(17:0), n-oleoyl threonine, 12-hydroxydodecanoic acid and tetracosahexaenoic acid) were selected as candidate biomarkers for CC. The AUC value, sensitivity (SE), and specificity (SP) of these 5 biomarkers were 0.99, 0.98 and 0.99, respectively. We further analysed the genes in 7 significantly enriched pathways, of which 117 genes, that were expressed differentially, were mainly involved in catalytic activity. Finally, a fully connected network of metabolites and genes in these pathways was built, which can increase the credibility of our selected metabolites. In conclusion, our biomarkers from metabolomics could set a path for CC diagnosis and screening. Our results also showed that variables of both transcriptomics and metabolomics were associated with CC.
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http://dx.doi.org/10.1038/srep43353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320559PMC
February 2017

Distinct plasma lipids profiles of recurrent ovarian cancer by liquid chromatography-mass spectrometry.

Oncotarget 2017 Jul;8(29):46834-46845

Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin 150086, P.R. China.

Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy worldwide due to its high recurrence rate after surgery and chemotherapy. There is a critical need for discovery of novel biomarkers for EOC recurrence providing higher prediction power than that of the present ones. Lipids have been reported to associate with development and progression of cancer. In the current study, we aim to identify and validate the lipids which were relevant to the ovarian cancer recurrence based on plasma lipidomics performed by ultra-performance liquid chromatography coupled with mass spectrometry. In order to fulfill this objective, plasma from 70 EOC patients with follow up information was obtained. The results revealed that patients with and without recurrence could be clearly distinguished based on their lipid profiles. Thirty-one lipid metabolites were identified as potential biomarkers for EOC recurrence. The AUC value of these metabolite combinations for predicting EOC recurrence was 0.897. In terms of clinical applicability, LysoPG(20:5) arose as a potential EOC recurrence predictive biomarker to increase the predictive power of clinical predictors from AUC value 0.739 to 0.875. Additionally, we still found that individuals with early relapses (< 6 months) had a distinctive metabolomic pattern compared with late EOC and non-EOC recurrence subjects. Interestingly, decreased levels of triglycerides (TGs) were found to be a specific metabolic feature foreshadowing an early relapse. In conclusion, plasma lipidomics study could be used for predicting EOC recurrences, as well as early and late recurrent cases. The lipid biomarker research improves the predictive power of clinical predictors and the identified biomarkers are of great prognostic and therapeutic potential.
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http://dx.doi.org/10.18632/oncotarget.11603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564526PMC
July 2017

Large radius of curvature measurement based on virtual quadratic Newton rings phase-shifting moiré-fringes measurement method in a nonnull interferometer.

Appl Opt 2016 Jun;55(17):4769-75

We have proposed a virtual quadratic Newton rings phase-shifting moiré-fringes measurement method in a nonnull interferometer to measure the large radius of curvature for a spherical surface. In a quadratic polar coordinate system, linear carrier testing Newton rings interferogram and virtual Newton rings interferogram form the moiré fringes. It is possible to retrieve the wavefront difference data between the testing and standard spherical surface from the moiré fringes after low-pass filtering. Based on the wavefront difference data, we deduced a precise formula to calculate the radius of curvature in the quadratic polar coordinate system. We calculated the retrace error in the nonnull interferometer using the multi-configuration model of the nonnull interferometric system in ZEMAX. Our experimental results indicate that the measurement accuracy is better than 0.18% for a spherical mirror with a radius of curvature of 41,400 mm.
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http://dx.doi.org/10.1364/AO.55.004769DOI Listing
June 2016

Metabolic phenotyping for monitoring ovarian cancer patients.

Sci Rep 2016 Mar 21;6:23334. Epub 2016 Mar 21.

Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin 150086, P.R. China.

Epithelial ovarian cancer (EOC) is the most deadly of the gynecological cancers. New approaches and better tools for monitoring treatment efficacy and disease progression of EOC are required. In this study, metabolomics using rapid resolution liquid chromatography mass spectrometry was applied to a systematic investigation of metabolic changes in response to advanced EOC, surgery and recurrence. The results revealed considerable metabolic differences between groups. Moreover, 37, 30, and 26 metabolites were identified as potential biomarkers for primary, surgical and recurrent EOC, respectively. Primary EOC was characterized by abnormal lipid metabolism and energy disorders. Oxidative stress and surgical efficacy were clear in the post-operative EOC patients. Recurrent EOC patients showed increased amino acid and lipid metabolism compared with primary EOC patients. After cytoreductive surgery, eight metabolites (e.g. l-kynurenine, retinol, hydroxyphenyllactic acid, 2-octenoic acid) corrected towards levels of the control group, and four (e.g. hydroxyphenyllactic acid, 2-octenoic acid) went back again to primary EOC levels after disease relapse. In conclusion, this study delineated metabolic changes in response to advanced EOC, surgery and recurrence, and identified biomarkers that could facilitate both understanding and monitoring of EOC development and progression.
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http://dx.doi.org/10.1038/srep23334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800393PMC
March 2016

Carrier squeezing interferometry with π/4 phase shift: phase extraction in the presence of multi-beam interference.

Appl Opt 2016 Mar;55(8):1920-8

Multi-beam interference exists in testing high-reflectivity surfaces with a Fizeau interferometer. In this paper, the multi-beam interference intensity was estimated as the sum of the first six order harmonics using the Fourier series expansion. Then, by adopting carrier squeezing interferometry with a π/4 phase shift, an algorithm was proposed to extract the phase from multi-beam interferograms. To ensure the separation of the lobes of phase-shift errors and the phase in the frequency domain, conditions of the necessary linear carrier in the proposed algorithm were derived. Simulation results indicated that the phase retrieving precision is better than PV 0.008λ and RMS 0.001λ, even when the reflection coefficient of the test surface is as high as 0.9 and the phase shift varies within π/4±π/20. Compared with the other algorithms, the proposed algorithm for multi-beam interference was validated by its good performance in the experiments, especially when the phase-shift error exists.
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http://dx.doi.org/10.1364/AO.55.001920DOI Listing
March 2016

The therapeutic effects of sodium cromoglycate against influenza A virus H5N1 in mice.

Influenza Other Respir Viruses 2016 Jan;10(1):57-66

Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Objectives: To identify the protective role of sodium cromoglycate in mice during influenza virus infection.

Design: H5N1 virus-infected mice were treated with the mast cell stabilizer sodium cromoglycate (SCG) to investigate its therapeutic effect.

Sample: The nose, trachea and lungs from mice were collected.

Main Outcome Measures: Virus replication and host responses were determined by plaque assay, quantitative PCR, immunohistochemistry, and histology.

Results: SCG-treated mice survived better than did PBS-treated mice after H5N1 virus infection. Mild pathological changes with fewer inflammatory cell infiltration and fewer virus antigens were observed in the nose, trachea, and lungs of SCG-treated mice on days 3 and 5 post-infection. However, no significant changes in viral load in the lungs were detected between SCG- and PBS-treated mice. Furthermore, significantly decreased expression of interleukin-6, tumor necrosis factor-a, Toll-like receptor 3, and TIR-domain-containing adapter-inducing interferon-b was detected in the lungs of SCG-treated mice, and no higher expression of interferon-c was detected.

Conclusion: These results suggest that SCG has therapeutic roles in H5N1 virus-infected mice by alleviating the inflammatory response rather than inhibition of viral replication in the lungs.
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http://dx.doi.org/10.1111/irv.12334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687497PMC
January 2016

Small intestinal injury in mice infected with respiratory influenza A virus: evidence for virus induced gastroenteritis.

Biotechnol Lett 2015 Aug 13;37(8):1585-92. Epub 2015 May 13.

Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China,

Objectives: Influenza in humans is often accompanied by gastroenteritis-like symptoms such as diarrhea and abdominal pain nausea, but the underlying mechanism remains unclear.

Results: Mice infected with three subtypes of respiratory influenza A virus (IAV), particularly H5N1 and H7N2, developed intestinal injury. The avian H5N1 and H7N2 IAV were detected in the small intestine, whereas the human H1N1 was not detected. Section staining with the sialic acid (SA) receptor demonstrated that the small intestine mainly expressed SA α2, 3 Gal instead of SA α2, 6 Gal which preferentially binds to avian IAV. The number of goblet and sIgA cells in the small intestine increased, whereas CD4(+) and CD8(+) T cells decreased in all infected mice except for CD8(+) T cells increased in H7N2 infected mice.

Conclusions: Respiratory IAV infection, particularly infected by avian IAV, can cause small intestine structural damage and modify the local immune response, thereby resulting in gastroenteritis-like symptoms.
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http://dx.doi.org/10.1007/s10529-015-1847-8DOI Listing
August 2015

Comparative assessment of orthogonal polynomials for wavefront reconstruction over the square aperture.

J Opt Soc Am A Opt Image Sci Vis 2014 Oct;31(10):2304-11

Four orthogonal polynomials for reconstructing a wavefront over a square aperture based on the modal method are currently available, namely, the 2D Chebyshev polynomials, 2D Legendre polynomials, Zernike square polynomials and Numerical polynomials. They are all orthogonal over the full unit square domain. 2D Chebyshev polynomials are defined by the product of Chebyshev polynomials in x and y variables, as are 2D Legendre polynomials. Zernike square polynomials are derived by the Gram-Schmidt orthogonalization process, where the integration region across the full unit square is circumscribed outside the unit circle. Numerical polynomials are obtained by numerical calculation. The presented study is to compare these four orthogonal polynomials by theoretical analysis and numerical experiments from the aspects of reconstruction accuracy, remaining errors, and robustness. Results show that the Numerical orthogonal polynomial is superior to the other three polynomials because of its high accuracy and robustness even in the case of a wavefront with incomplete data.
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http://dx.doi.org/10.1364/JOSAA.31.002304DOI Listing
October 2014