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1.
Nat Commun ; 14(1): 7393, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37968364

ABSTRACT

The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg and/or young ages, is still unresolved due to the lack of surrogate models. Here, we generate a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrate that human IFN stimulates gene expression profiles in huIFNAR peripheral blood mononuclear cells (PBMCs) are similar to those in human PBMCs, supporting the representativeness of this mouse model for functionally analyzing human IFN in vivo. Next, we reveal the tissue-specific gene expression atlas across multiple organs in response to human IFN treatment; this pattern has not been reported in healthy humans in vivo. Finally, by using the AAV-HBV model, we test the antiviral effects of human interferon. Fifteen weeks of human PEG-IFNα2 treatment significantly reduces HBsAg and HBeAg and even achieves HBsAg seroconversion. We observe that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon may be critical for HBsAg suppression. Our huIFNAR mouse can authentically respond to human interferon stimulation, providing a platform to study interferon function in vivo. PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieves HBsAg seroconversion.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Mice , Animals , Hepatitis B virus/physiology , Hepatitis B Surface Antigens , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Interferon-alpha/pharmacology , Interferon-alpha/therapeutic use , Leukocytes, Mononuclear/metabolism , Recombinant Proteins/pharmacology , Polyethylene Glycols/pharmacology , DNA, Viral , Treatment Outcome
2.
J Med Virol ; 95(1): e28219, 2023 01.
Article in English | MEDLINE | ID: mdl-36229892

ABSTRACT

Retest-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA, as a unique phenomenon among discharged individuals, has been demonstrated to be safe in the community. Still, the underlying mechanism of viral lingering is less investigated. In this study, first, we find that the frequency of viral RNA-positive retesting differs among variants. Higher ratios of viral RNA-positive retest were more frequently observed among Delta (61.41%, 514 of 837 cases) and Omicron (39.53%, 119 of 301 cases) infections than among ancestral viral infection (7.27%, 21 of 289 cases). Second, the tissues where viral RNA reoccurred were altered. Delta RNA reoccurred mainly in the upper respiratory tract (90%), but ancestral virus RNA reoccurred mainly in the gastrointestinal tract (71%). Third, vaccination did not reduce the frequency of viral RNA-positive retests, despite high concentrations of viral-specific antibodies in the blood. Finally, 37 of 55 (67.27%) Delta-infected patients receiving neutralizing antibody therapy become viral RNA retest positive when high concentrations of neutralizing antibodies still patrol in the blood. Altogether, our findings suggest that the presentence of high titers of neutralizing antibodies in the blood is incompetent in clearing residual viral RNA in the upper respiratory tract.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Antibodies, Neutralizing , Trachea , RNA, Viral/genetics , Antibodies, Viral , Spike Glycoprotein, Coronavirus
3.
Sci Prog ; 105(4): 368504221137461, 2022.
Article in English | MEDLINE | ID: mdl-36514818

ABSTRACT

The identification of the film on cotton is of great significance for the improvement of cotton quality. Most of the existing technologies are dedicated to removing colored foreign fibers from cotton using photoelectric sorting methods. However, the current technologies are difficult to identify colorless transparent film, which becomes an obstacle for the harvest of high-quality cotton. In this paper, an intelligent identification method is proposed to identify the colorless and transparent film on cotton, based on short-wave near-infrared hyperspectral imaging and convolutional neural network (CNN). The algorithm includes black-and-white correction of hyperspectral images, hyperspectral data dimensionality reduction, CNN model training and testing. The key technology is that the features of the hyperspectral image data are degraded by the principal component analysis (PCA) to reduce the amount of computing time. The main innovation is that the colorless and transparent film on cotton can be accurately identified through a CNN with the performance of automatic feature extraction. The experimental results show that the proposed method can greatly improve the identification precision, compared with the traditional methods. After the simulation experiment, the method proposed in this paper has a recognition rate of 98.5% for film. After field testing, the selection rate of film is as high as 96.5%, which meets the actual production needs.


Subject(s)
Hyperspectral Imaging , Neural Networks, Computer , Principal Component Analysis , Algorithms , Motion Pictures
4.
Nat Commun ; 12(1): 4984, 2021 08 17.
Article in English | MEDLINE | ID: mdl-34404803

ABSTRACT

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Spike Glycoprotein, Coronavirus/immunology
5.
Exp Ther Med ; 13(4): 1275-1278, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28413466

ABSTRACT

A clinical analysis of diagnosis was performed as well as the management of orbital foreign bodies, to investigate the methods to avoid missed diagnosis. A total of 15 cases of an orbital foreign body was reviewed, and for these cases, the clinical manifestation, imaging data and operative situation were studied. Among the patients, 4 cases turned out to have wooden, 3 metallic, 2 glass, 2 bones, and 4 other foreign bodies. Twelve cases had received debridement and suture before our management, and 1 foreign body was treated more than once. In conclusion, detailed traumatic history and imaging examination are necessary for the diagnosis of orbital foreign bodies, while prompt diagnosis, accurate location and professional surgical skills are important for the treatment.

6.
Plant Cell ; 25(11): 4755-66, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24285796

ABSTRACT

Multicellular eukaryotic organisms are attacked by numerous parasites from diverse phyla, often simultaneously or sequentially. An outstanding question in these interactions is how hosts integrate signals induced by the attack of different parasites. We used a model system comprised of the plant host Arabidopsis thaliana, the hemibiotrophic bacterial phytopathogen Pseudomonas syringae, and herbivorous larvae of the moth Trichoplusia ni (cabbage looper) to characterize mechanisms involved in systemic-induced susceptibility (SIS) to T. ni herbivory caused by prior infection by virulent P. syringae. We uncovered a complex multilayered induction mechanism for SIS to herbivory. In this mechanism, antiherbivore defenses that depend on signaling via (1) the jasmonic acid-isoleucine conjugate (JA-Ile) and (2) other octadecanoids are suppressed by microbe-associated molecular pattern-triggered salicylic acid (SA) signaling and infection-triggered ethylene signaling, respectively. SIS to herbivory is, in turn, counteracted by a combination of the bacterial JA-Ile mimic coronatine and type III virulence-associated effectors. Our results show that SIS to herbivory involves more than antagonistic signaling between SA and JA-Ile and provide insight into the unexpectedly complex mechanisms behind a seemingly simple trade-off in plant defense against multiple enemies.


Subject(s)
Arabidopsis/metabolism , Arabidopsis/microbiology , Ethylenes/metabolism , Herbivory , Animals , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Carboxylic Ester Hydrolases/genetics , Carboxylic Ester Hydrolases/metabolism , Cyclopentanes/metabolism , Gene Expression Regulation, Plant , Isoleucine/metabolism , Moths , Mutation , Oxylipins/metabolism , Plant Leaves , Pseudomonas syringae/pathogenicity , Salicylic Acid/metabolism , Signal Transduction
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 31(10): 1346-8, 2011 Oct.
Article in Chinese | MEDLINE | ID: mdl-22097202

ABSTRACT

OBJECTIVE: To assess the intervention of Biantong Huangqi Ointment (BHO) combined with Western medicine (WM) on the recurrence of bronchial asthma (BA). METHODS: Eighty-four BA children patients were randomly assigned to the treatment group (43 cases) and the control group (41 cases). During the period of onset, patients in the two groups were treated by WM alone. During the remission phase, patients in the treatment group took BHO, one dose daily, while those in the control group were treated with atomized inhalation of Budesonide and Salbutamol (0.5 mL each time for those 3 -8 years old; 0.75 mL each time for >or=those 8-12 years old). The therapeutic course for them all was 1 month. The serum levels of IgG and IgE before and after treatment, 6 and 12 months after withdrawal of medication were detected in the two groups, and the recurrence rate of BA observed in the two groups. RESULTS: The recurrence rate of the treatment group was obviously lower than that of the control group after withdrawal of medication (9.5% vs 24.4% for 6 months, 14.0% vs 34.1% for 12 months), showing statistical difference between the two groups (P<0.05). The serum IgG level of children patients in the treatment group increased continuously after medication. The high serum IgE level state obtained long-term and effective relief. CONCLUSION: BHO showed favorable anti-recurrent effect on children's BA. Its mechanism might be associated with regulating children's immune system.


Subject(s)
Asthma/drug therapy , Drugs, Chinese Herbal/therapeutic use , Asthma/etiology , Child , Child, Preschool , Female , Humans , Integrative Medicine , Male , Ointments , Recurrence , Treatment Outcome
8.
Proc Natl Acad Sci U S A ; 102(5): 1791-6, 2005 Feb 01.
Article in English | MEDLINE | ID: mdl-15657122

ABSTRACT

Many pathogens are virulent because they specifically interfere with host defense responses and therefore can proliferate. Here, we report that virulent strains of the bacterial phytopathogen Pseudomonas syringae induce systemic susceptibility to secondary P. syringae infection in the host plant Arabidopsis thaliana. This systemic induced susceptibility (SIS) is in direct contrast to the well studied avirulence/R gene-dependent resistance response known as the hypersensitive response that elicits systemic acquired resistance. We show that P. syringae-elicited SIS is caused by the production of coronatine (COR), a pathogen-derived functional and structural mimic of the phytohormone jasmonic acid (JA). These data suggest that SIS may be a consequence of the previously described mutually antagonistic interaction between the salicylic acid and JA signaling pathways. Virulent P. syringae also has the potential to induce net systemic susceptibility to herbivory by an insect (Trichoplusia ni, cabbage looper), but this susceptibility is not caused by COR. Rather, consistent with its role as a JA mimic, COR induces systemic resistance to T. ni. These data highlight the complexity of defense signaling interactions among plants, pathogens, and herbivores.


Subject(s)
Arabidopsis/microbiology , Pseudomonas syringae/physiology , Animals , Arabidopsis/parasitology , Disease Susceptibility , Insecta/parasitology , Models, Biological , Plant Diseases/microbiology , Plant Diseases/parasitology , Pseudomonas syringae/pathogenicity , Virulence
9.
Plant Physiol ; 129(2): 551-64, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12068100

ABSTRACT

Plants have evolved different but interconnected strategies to defend themselves against herbivorous insects and microbial pathogens. We used an Arabidopsis/Pseudomonas syringae pathosystem to investigate the impact of pathogen-induced defense responses on cabbage looper (Trichoplusia ni) larval feeding. Arabidopsis mutants [npr1, pad4, eds5, and sid2(eds16)] or transgenic plants (nahG) that are more susceptible to microbial pathogens and are compromised in salicylic acid (SA)-dependent defense responses exhibited reduced levels of feeding by T. ni compared with wild-type plants. Consistent with these results, Arabidopsis mutants that are more resistant to microbial pathogens and have elevated levels of SA (cpr1 and cpr6) exhibited enhanced levels of T. ni feeding. These experiments suggested an inverse relationship between an active SA defense pathway and insect feeding. In contrast to these results, there was increased resistance to T. ni in wild-type Arabidopsis ecotype Columbia plants that were infected with P. syringae pv. maculicola strain ES4326 (Psm ES4326) expressing the avirulence genes avrRpt2 or avrB, which elicit a hypersensitive response, high levels of SA accumulation, and systemic acquired resistance to bacterial infection. Similar results were obtained with other ecotypes, including Landsberg erecta, Cape Verdi Islands, and Shakdara. When infected with Psm ES4326(avrRpt2) or Psm ES4326(avrB), nahG transgenic and npr1 mutant plants (which are more susceptible to virulent and avirulent P. syringae strains) failed to show the increased insect resistance exhibited by wild-type plants. It was surprising that wild-type plants, as well as nahG and npr1 plants, infected with Psm ES4326 not expressing avrRpt2 or avrB, which elicits disease, became more susceptible to T. ni. Our results suggest two potentially novel systemic signaling pathways: a systemic response elicited by HR that leads to enhanced T. ni resistance and overrides the SA-mediated increase in T. ni susceptibility, and a SA-independent systemic response induced by virulent pathogens that leads to enhanced susceptibility to T. ni.


Subject(s)
Arabidopsis/microbiology , Lepidoptera/growth & development , Plant Diseases/microbiology , Pseudomonas/growth & development , Signal Transduction/physiology , Animals , Arabidopsis/genetics , Arabidopsis/parasitology , Bacterial Proteins/genetics , Feeding Behavior/physiology , Host-Parasite Interactions , Immunity, Innate , Larva/growth & development , Mutation , Plant Diseases/parasitology , Plant Leaves/microbiology , Plant Leaves/parasitology , Plants, Genetically Modified , Pseudomonas/pathogenicity , Salicylic Acid/metabolism , Virulence
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