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1.
J Virol ; 97(4): e0026423, 2023 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-36943051

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory disease in pigs of all ages and reproductive failure in sows, resulting in great economic losses to the swine industry. In this work, we identified the interaction between PSMB4 and PRRSV Nsp1α by yeast two-hybrid screening. The PSMB4-Nsp1α interaction was further confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown, and laser confocal experiments. The PCPα domain (amino acids 66 to 166) of Nsp1α and the C-terminal domain (amino acids 250 to 264) of PSMB4 were shown to be critical for the PSMB4-Nsp1α interaction. PSMB4 overexpression reduced PRRSV replication, whereas PSMB4 knockdown elicited opposing effects. Mechanistically, PSMB4 targeted K169 in Nsp1α for K63-linked ubiquitination and targeted Nsp1α for autolysosomal degradation by interacting with LC3 to enhance the activation of the lysosomal pathway. Meanwhile, we found that PSMB4 activated the NF-κB signaling pathway to produce type I interferons by downregulating the expression of IκBα and p-IκBα. In conclusion, our data revealed a new mechanism of PSMB4-mediated restriction of PRRSV replication, whereby PSMB4 was found to induce Nsp1α degradation and type I interferon expression, in order to impede the replication of PRRSV. IMPORTANCE In the swine industry, PRRSV is a continuous threat, and the current vaccines are not effective enough to block it. This study determined that PSMB4 plays an antiviral role against PRRSV. PSMB4 was found to interact with PRRSV Nsp1α, mediate K63-linked ubiquitination of Nsp1α at K169, and thus trigger its degradation via the lysosomal pathway. Additionally, PSMB4 activated the NF-κB signaling pathway to produce type I interferons by downregulating the expression of IκBα and p-IκBα. This study extends our understanding of the proteasome subunit PSMB4 against PRRSV replication and will contribute to the development of new antiviral strategies.


Asunto(s)
Interferón Tipo I , Virus del Síndrome Respiratorio y Reproductivo Porcino , Complejo de la Endopetidasa Proteasomal , Proteínas no Estructurales Virales , Expresión Génica/inmunología , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Interferón beta/genética , Lisosomas/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/inmunología , Dominios Proteicos , Proteolisis , Porcinos , Ubiquitinación , Proteínas no Estructurales Virales/metabolismo , Replicación Viral/genética , Animales
2.
Virol J ; 15(1): 119, 2018 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-30071879

RESUMEN

BACKGROUND: The alphaherpesvirus virion host shutoff (vhs) gene, UL41, can induce degradation of host mRNAs and shut off host protein synthesis. The roles of vhs in HSV-1 and HSV-2 have been studied extensively in previous studies, however, relatively little is known about the vhs protein of PRV. METHODS: A novel method combining CRISPR/Cas9 and Gibson assembly was developed to generate UL41 null PRV variant. The properties of UL41 null PRV in vitro and in vivo were further characterized. And the vhs activity of UL41 protein of PRV variant was evaluated by luciferase assay, Western-blot and RT-qPCR. RESULTS: Gibson assembly based on homologous recombination can accomplish one-step insertion of viral DNA fragments into donor plasmids efficiently (> 80%). Cas9/gRNA further largely enhanced the efficiency of homologous recombination. Using this method we were able to rapidly generate the UL41 null and revertant viruses of PRV variant. Compared to wild type (JS-2012), the UL41 null virus showed significantly smaller plaques and lower titers in Vero cells and impaired lethality and neuroinvasion in mice. Further the UL41 protein from different PRV strains exhibited unequal vhs activity in vitro, which of JS-2012 showed significantly weaker vhs activity than that of European-American strains. In addition UL41 null virus can also significantly decrease the expression of host genes during the early period of infection, which suggests other viral factors may be also involved in host shutoff. CONCLUSIONS: CRISPR/Cas9 combined with Gibson assembly efficiently generated UL41 null PRV. Compared to wild type, UL41 null PRV showed impaired both replication capability in vitro and neuroinvasion in vivo. Further UL41 protein of PRV variant showed significantly weaker vhs activity than that of PRV SC (European-American-like strain), suggesting the deficiency of vhs activity by the PRV variant UL41 protein.


Asunto(s)
Eliminación de Gen , Infecciones por Herpesviridae/virología , Herpesvirus Suido 1/genética , Proteínas Virales/genética , Animales , Bovinos , Línea Celular , Chlorocebus aethiops , Efecto Citopatogénico Viral , Variación Genética , Células HEK293 , Infecciones por Herpesviridae/genética , Herpesvirus Suido 1/patogenicidad , Herpesvirus Suido 1/fisiología , Humanos , Ratones , Ratones Endogámicos BALB C , Neuronas/virología , Biosíntesis de Proteínas/genética , Tasa de Supervivencia , Porcinos , Células Vero , Proteínas Virales/metabolismo , Replicación Viral
3.
Environ Toxicol ; 29(1): 108-16, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21953684

RESUMEN

Benzene is an important industrial chemical that is also widely present in cigarette smoke, automobile exhaust, and gasoline. It is reported that benzene can cause hematopoietic disorders and has been recognized as a human carcinogen. However, the mechanisms by which it increases the risk of carcinogenesis are only partially understood. Aberrant DNA methylation is a major epigenetic mechanism associated with the toxicity of carcinogens. To understand the carcinogenic capacity of benzene, experiments were designed to investigate whether exposure to benzene and its metabolites would change the global DNA methylation status in human normal hepatic L02 cells and then to evaluate whether the changes would be induced by variation of DNA methyltransferase (DNMT) activity in HaeIII DNMT-mediated methylation assay in vitro. Our results showed that hydroquinone and 1,4-benzoquinone could induce global DNA hypomethylation with statistically significant difference from control (p < 0.05), but no significant global DNA methylation changes were observed in L02 cells with benzene, phenol, and 1,2,4-trihydroxybenzene exposure. Benzene metabolites could not influence HaeIII DNMT activity except that 1,4-benzoquinone shows significantly inhibiting effect on enzymatic methylation reaction at concentrations of 5 µM (p < 0.05). These results suggest that benzene metabolites, hydroquinone, and 1,4-benzoquinone can disrupt global DNA methylation, and the potential epigenetic mechanism by which that global DNA hypomethylation induced by 1,4-benzoquinone may work through the inhibiting effects of DNMT activity at 10 µM (p < 0.05).


Asunto(s)
Derivados del Benceno/toxicidad , Benceno/toxicidad , Carcinogénesis/inducido químicamente , Metilación de ADN/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Benceno/metabolismo , Carcinógenos/toxicidad , Línea Celular , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Epigénesis Genética/efectos de los fármacos , Humanos
4.
Front Public Health ; 11: 1170782, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37333524

RESUMEN

Objective: As China's population aging process accelerates, the expenditure of China's basic medical insurance fund for employees may increase significantly, which may threaten the sustainability of China's basic medical insurance fund for employees. This paper aims to forecast the future development of China's basic medical insurance fund for employees in the context of the increasingly severe aging of the population. Methods: This paper taking an empirical study from Shanghai as an example, constructs an actuarial model to analyze the impact of changes in the growth rate of per capita medical expenses due to non-demographic factors and in the population structure on the sustainability of the basic medical insurance fund for employees. Results: Shanghai basic medical insurance fund for employees can achieve the goal of sustainable operation in 2021-2035, with a cumulative balance of 402.150-817.751 billion yuan in 2035. The lower the growth rate of per capita medical expenses brought about by non-demographic factors, the better the sustainable operation of the fund. Conclusion: Shanghai basic medical insurance fund for employees can operate sustainably in the next 15 years, which can further reduce the contribution burden of enterprises, which lays the foundation for improving the basic medical insurance treatment for employees.


Asunto(s)
Administración Financiera , Seguro , Humanos , China/epidemiología , Dinámica Poblacional , Envejecimiento
5.
Vet Microbiol ; 281: 109741, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37087878

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus belonging to the Arteriviridae family. Currently, the strain has undergone numerous mutations, bringing massive losses to the swine industry worldwide. Despite several studies had been conducted on PRRSV, the molecular mechanisms by which it causes infection remain unclear. Proliferating cell nuclear antigen (PCNA) is a sign of DNA damage and it participates in DNA replication and repair. Therefore, in this study, we investigated the potential role of PCNA in PRRSV infection. We observed that PCNA expression was stable after PRRSV infection in vitro; however, PCNA was translocated from the nucleus to the cytoplasm. Notably, we found the redistribution of PCNA from the nucleus to the cytoplasm in cells transfected with the N protein. PCNA silencing inhibited PRRSV replication and the synthesis of PRRSV shorter subgenomic RNA (sgmRNA) and genomic RNA (gRNA), while PCNA overexpression promoted virus replication and PRRSV shorter sgmRNA and gRNA synthesis. By performing immunoprecipitation and immunofluorescence colocalization, we confirmed that PCNA interacted with replication-related proteins, namely NSP9, NSP12, and N, but not with NSP10 and NSP11. Domain III of the N protein (41-72 aa) interacted with the IDCL domain of PCNA (118-135 aa). Therefore, we propose cytoplasmic transport of PCNA and its subsequent influence on PRRSV RNA synthesis could be a viral strategy for manipulating cell function, thus PCNA is a potential target to prevent and control PRRSV infection.


Asunto(s)
Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Enfermedades de los Porcinos , Animales , Genoma Viral , Síndrome Respiratorio y de la Reproducción Porcina/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/metabolismo , Antígeno Nuclear de Célula en Proliferación/genética , ARN , Porcinos , Enfermedades de los Porcinos/genética , Proteínas no Estructurales Virales/genética , Replicación Viral/genética , ARN Subgenómico/genética
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(10): 817-20, 2012 Oct.
Artículo en Zh | MEDLINE | ID: mdl-23302666

RESUMEN

OBJECTIVES: To evaluate the feasibility and efficacy of transcatheter closure of perimembranous ventricular septal defects (pmVSD) with aneurysmatic formation and muscular ventricular septal defects (mVSD) with Amplatzer duct occluder II. METHODS: This retrospective analysis included 48 cases received transcatheter closure of pmVSD aneurysmatic formation or mVSD from February 2011 to March 2012 in our hospital (42 pmVSD with aneurysmatic formation and 6 mVSD). Median age was 5.2 years (range: 1.8 - 15 years), and median weight was 20.2 kg (range: 12 - 44 kg). Amplatzer duct occluder II was selected depending on the condition of ventricular septal defect. The device was implanted by antegrade or retrograde approach. Complications such as residual shunt, valvular regurgitation and arrhythmia were evaluated by echocardiography or angiography. Median follow-up was 9.5 months (range: 1 - 13 months). RESULTS: The mean ratio of pulmonary (Qp) to systemic (Qs) blood flow was 1.35 ± 0.15 before transcatheter closure. The diameter of exit hole of ventricular septal defects was (2.46 ± 0.53) mm measured by transthoracic echocardiography, and (2.35 ± 0.40) mm by angiography. Successful implantation of the device was achieved in 46 patients (96%) and unsuccessful in two cases due to acute aortic insufficiency. Forty-two (92%) patients were closed successfully, and trivial residual leak was evidenced in four patients and remained unchanged during follow-up. One patient with mVSD still had trivial residual shunt at 6 months post procedure. New trivial tricuspid insufficiency was observed in 1 patient (2.1%) during follow-up. Two patients developed procedural related left anterior fascicular block and remained unchanged during follow-up. CONCLUSIONS: pmVSD with aneurysm and mVSD could be successfully treated with Amplatzer duct occluder II. However, the long waist and large disc of the device could interfere with tricuspid valve function and cause tricuspid insufficiency.


Asunto(s)
Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/métodos , Defectos del Tabique Interventricular/cirugía , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Dispositivo Oclusor Septal , Resultado del Tratamiento
7.
Front Public Health ; 10: 1014470, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36268004

RESUMEN

Background: The reinfection rate of SARS-CoV-2 Omicron variant is high; thus, exploring the risk factors for reinfection is important for the effective control of the epidemic. This study aimed to explore the effects of psychological and sleep factors on re-positivity with Omicron. Methods: Through a prospective cohort study, 933 adult patients diagnosed with Omicron BA.2.2 infection and testing negative after treatment were included for screening and follow-up. We collected data on patients' demographic characteristics, SARS-CoV-2 Omicron vaccination status, anxiety, depression, and sleep status. Patients underwent nucleic acid testing for SARS-CoV-2 Omicron for 30 days. Regression and Kaplan-Meier analyses were used to determine the risk factors for re-positivity of Omicron. Results: Ultimately, 683 patients were included in the analysis. Logistic regression analysis showed that older age (P = 0.006) and depressive status (P = 0.006) were two independent risk factors for Omicron re-positivity. The odds ratios of re-positivity in patients aged ≥60 years and with a Patient Health Questionnaire-9 (PHQ-9) score ≥5 was 1.82 (95% confidence interval:1.18-2.78) and 2.22 (1.27-3.85), respectively. In addition, the time from infection to recovery was significantly longer in patients aged ≥60 years (17.2 ± 4.5 vs. 16.0 ± 4.4, P = 0.003) and in patients with PHQ-9≥5 (17.5 ± 4.2vs. 16.2 ± 4.5, P = 0.026). Kaplan-Meier analysis showed that there was a significantly higher primary re-positivity rate in patients aged ≥60 years (P = 0.004) and PHQ-9 ≥ 5 (P = 0.007). Conclusion: This study demonstrated that age of ≥60 years and depressive status were two independent risk factors for re-positivity with Omicron and that these factors could prolong the time from infection to recovery. Thus, it is necessary to pay particular attention to older adults and patients in a depressive state.


Asunto(s)
COVID-19 , Ácidos Nucleicos , Humanos , Anciano , SARS-CoV-2 , Reinfección , Estudios Prospectivos , COVID-19/epidemiología , Factores de Riesgo
8.
Front Chem ; 10: 865375, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372288

RESUMEN

Experiments were carried out to research the different contents of Ga2O3 modification effects on the hydrodesulfurization (HDS) performance of 4,6-dimethyldibenzothiophene (4,6-DMDBT) catalyzed by the stepwise impregnation method. Characterization techniques such as XRD, BET, HRTEM, NH3-TPD, and Py-FTIR were performed to determine the effects of each modification of the catalyst by Ga on the properties of the prepared supports and catalysts. The catalytic effect of gallium is reflected in the fact that the empty d-orbitals of Ga elements participate in the formation of molecular orbitals in the active center and change their orbital properties, thus generating a direct desulfurization active phase suitable for complex sulfides for endpoint adsorption. The characterization results indicated that the introduction of Ga2O3 with appropriate content (2 wt.%) promoted Ni and Mo species to disperse uniformly and doping of more Ni atoms into the MoS2 crystals, which also increased the average stacking number and the length of MoS2. As a result, more NiMoS active phases were favored to form in the system. The specific surface area and the amounts of acid sites were increased, facilitating the adsorption of reactant molecules and the HDS reactions. The HDS results also suggested the effects of Ga modification play a very important role in the catalytic performance of the corresponding catalysts. The catalyst Ga-Ni-Mo/Al2O3 exhibited the highest conversion rate towards 4,6-DMDBT HDS when the amount of Ga2O3 loading was 2 wt.% with an LHSV of 2.5 h-1 at 290°C and Ga modification also can effectively improve the direct desulfurization (DDS) route selectivity in varying degrees.

9.
Front Vet Sci ; 9: 886058, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35619609

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses the innate immune response in the host, reducing and delaying neutralizing antibody production against PRRSV infection and promoting viral infection. Here, we aimed to assess the potential of Panax notoginseng saponins (PNS) for improving the immune response exerted upon PRRSV-2-modified live virus (MLV) vaccine administration. Thirty piglets were randomly divided into six groups. Group 1 piglets were injected with medium 0 days post vaccination (dpv). Group 2 piglets were fed PNS 0-28 dpv. Group 3 and group 4 piglets were administered the JXA1-R vaccine 0 dpv. Group 4 piglets were also fed PNS 0-28 dpv. Group 1-4 piglets were challenged intranasally with the PRRSV JXA1 strain 28 dpv. Group 5 piglets were fed with PNS without challenge. Group 6 piglets served as controls. During the experiment, the samples were collected regularly for 49 days. Compared with group 1 piglets, group 3 piglets showed significantly reduced viremia and clinical scores, and significantly increased average daily gain (ADWG). Compared with group 3 piglets, group 4 piglets showed significantly improved neutralizing antibody titers, IFN-α and IFN-ß mRNA expression, and significantly decreased viremia and viral load in the lungs and lymph nodes, but did not demonstrate any further improvement in PRRSV-specific antibody titer, rectal temperature, ADWG, or clinical scores. PNS upregulates neutralizing antibodies against PRRSV-2 and enhances the expression of IFN-α and IFN-ß, which may reduce PRRSV viremia upon PRRSV-2 MLV vaccine administration. PNS may serve as an effective immunomodulator for boosting the immune defense against PRRSV.

10.
Obes Surg ; 31(11): 5034-5043, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34505971

RESUMEN

This study aims to determine the long-term relapse rate of type 2 diabetes (T2DM) following initial remission after Roux-en-Y gastric bypass (RYGB) surgery. We searched studies in PubMed, Embase, and the Cochrane Library. A total of 17 eligible studies were included for analysis. Meta-analysis suggested a pooled long-term relapse rate of 0.30 (95% confidence interval [CI], 0.26-0.34) and a remission rate of 0.63 (95% CI, 0.55-0.72) after RYGB and a hazard ratio of 0.73 (95% CI, 0.66-0.81) for comparison of RYGB and sleeve gastrectomy (SG). Subgroup analyses established pooled results. This study suggested RYGB may be a preferred regime for obese patients with T2DM because it is associated with lower long-term relapse and relatively higher initial remission and was also superior to SG due to lower risk of recurrence.


Asunto(s)
Diabetes Mellitus Tipo 2 , Derivación Gástrica , Obesidad Mórbida , Diabetes Mellitus Tipo 2/cirugía , Gastrectomía , Humanos , Obesidad Mórbida/cirugía , Recurrencia , Resultado del Tratamiento
11.
Vet Microbiol ; 253: 108847, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360319

RESUMEN

Swine influenza viruses not only constitute a potential economic problem for livestock, but also pose a substantial threat to human health. Mutation in the proteolytic cleavage site of hemagglutinin (HA) is recognized as an essential factor of tissue tropism and viral pathogenicity. However, the molecular properties of the cleavage site of Eurasian avian-like swine (EA) H1N2 virus remain largely unknown. In this study, we found a serine-leucine (Ser-Leu) substitution at the P2 position of the HA cleavage site (S328 L) in naturally occurring EA H1N2 virus. To study the effect of this substitution, we used reverse genetics to generate recombinant wild-type and mutant viruses containing a single amino acid mutation at the P2 position in A/swine/Guangdong/YJ28/2014 (YJ28) or A/swine/Guangdong/DG2/2015 (DG2) background. In vitro experiments showed that the Ser-Leu substitution at the P2 position attenuated the viral replication and HA cleavage efficiency. In vivo analyses revealed that, while all mice inoculated with r/DG2-S328 L or r/YJ28 viruses survived, the survival rates of r/DG2- and r/YJ28-L328S-inoculated animals were 20 % and 40 %, respectively. Furthermore, the Ser-Leu substitution at the P2 position attenuated the replication in nasal turbinate and lungs. In summary, this amino acid change may be useful to understand the molecular properties of the cleavage site and be valuable for vaccine development.


Asunto(s)
Sustitución de Aminoácidos , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N2 del Virus de la Influenza A/patogenicidad , Leucina/metabolismo , Infecciones por Orthomyxoviridae/veterinaria , Serina/metabolismo , Replicación Viral/genética , Células A549 , Animales , Asia , Chlorocebus aethiops , Perros , Europa (Continente) , Femenino , Células HEK293 , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Subtipo H1N2 del Virus de la Influenza A/clasificación , Subtipo H1N2 del Virus de la Influenza A/genética , Subtipo H1N2 del Virus de la Influenza A/crecimiento & desarrollo , Gripe Humana/virología , Leucina/genética , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/virología , Serina/genética , Células Vero , Virulencia
12.
Echocardiography ; 27(7): 878-84, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20546003

RESUMEN

The objective of this study was to analyze the echocardiographic characteristics of juxtaposition of the atrial appendages and to determine its prevalence in children with congenital heart disease. From June 1998 to December 2008, 10,880 children underwent selective angiocardiography, magnetic resonance imaging (MRI), and echocardiography for evaluation of congenital heart disease. Juxtaposition of the atrial appendages was diagnosed based on the results of angiocardiography and MRI; the echocardiographic characteristics of this anomaly were analyzed retrospectively. There were 33 patients diagnosed with juxtaposition of the right atrial appendage (JRAA); no patient was diagnosed with juxtaposition of the left atrial appendage. The prevalence of JRAA in children with congenital heart disease was 0.30%. JRAA and abnormal spatial orientation of the atrial septum were visualized by Doppler echocardiography in 28 cases. In the remaining five cases, three cases with suspected JRAA could not be determined by echocardiography and the diagnosis was missed in two cases. The most common associated anomalies were conotruncal malformations (16 cases with double outlet of the right ventricle, 9 cases with pulmonary atresia, 6 cases with transposition of the great arteries, 1 case with tetralogy of Fallot) and tricuspid malformations (6 cases with tricuspid straddling, 3 cases with tricuspid atresia, 2 cases with tricuspid valve stenosis). Based on the characteristic alteration of the plane of the atrial septum and visualization of the malpositioned right atrial appendage, JRAA can be accurately diagnosed by Doppler echocardiography.


Asunto(s)
Apéndice Atrial/anomalías , Apéndice Atrial/diagnóstico por imagen , Ecocardiografía/estadística & datos numéricos , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/epidemiología , Adolescente , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Incidencia , Lactante , Masculino
13.
Viruses ; 12(1)2020 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-31906472

RESUMEN

The Eurasian avian-like swine (EA) H1N1 virus has affected the Chinese swine industry, and human infection cases have been reported occasionally. However, little is known about the pathogenic mechanism of EA H1N1 virus. In this study, we compared the mouse pathogenicity of A/swine/Guangdong/YJ4/2014 (YJ4) and A/swine/Guangdong/MS285/2017 (MS285) viruses, which had similar genotype to A/Hunan/42443/2015 (HuN-like). None of the mice inoculated with 106 TCID50 of YJ4 survived at 7 days post infection, while the survival rate of the MS285 group was 100%. Therefore, a series of single fragment reassortants in MS285 background and two rescued wild-type viruses were generated by using the reverse genetics method, and the pathogenicity analysis revealed that the PB2 gene contributed to the high virulence of YJ4 virus. Furthermore, there were 11 amino acid differences in PB2 between MS285 and YJ4 identified by sequence alignment, and 11 single amino acid mutant viruses were generated in the MS285 background. We found that the R251K mutation significantly increased the virulence of MS285 in mice, contributed to high polymerase activity and enhanced viral genome transcription and replication. These results indicate that PB2-R251K contributes to the virulence of the EA H1N1 virus and provide new insight into future molecular epidemiological surveillance strategies.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Infecciones por Orthomyxoviridae/virología , ARN Polimerasa Dependiente del ARN/genética , Proteínas Virales/genética , Replicación Viral/genética , Células A549 , Sustitución de Aminoácidos , Animales , Perros , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/fisiología , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/patología , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas Virales/metabolismo , Virulencia/genética
14.
Transbound Emerg Dis ; 67(6): 2630-2641, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32386249

RESUMEN

The newly emerged lineage 1 porcine reproductive and respiratory syndrome viruses (PRRSVs) (especially the NADC30-like and NADC34-like viruses) have posed a direct threat to the Chinese pig industry since 2013. The phylogenetic, epidemic, and recombinant properties of these viruses have not yet systematically analysed in China. This report presents regular surveillance and field epidemiological studies for PRRSV across China from 2007 to 2019. From over 4,000 detected clinical samples, 70 open reading frame five sequences and four complete genomes of lineage 1 viruses were successfully obtained. Combined with global data, we conducted an extensive and systematic molecular phylogeny analysis using a maximum likelihood tree. The Chinese lineage 1 viruses were clustered, and their temporal and spatial distribution was further explored. Multiple viral introductions of lineage 1 virus from the United States to China were detected, and some became endemic in China. There are three sub-lineage 1 clusters: lineage 1.5 (NADC34-like), lineage 1.6 and New Intro cluster (NADC30-like). These viruses show high genetic diversity and a wide distribution in China, with Henan Province showing the highest diversity. Moreover, Chinese lineage 1 viruses have developed an endemic NADC30-like cluster. The demographic feature of this cluster showed a more or less constant population expansion history with a recent decreasing trend. Moreover, the genome recombination of Chinese lineage 1 with two dominant clusters (Chinese HP-PRRSVs: lineage 8.7 and VR2332-like: lineage 5.1) was frequently detected, both of which have commercial vaccine strains available. Furthermore, recombination hotspots were discovered near NSP9 and ORF2-4 regions of the genome. Overall, these findings provide important insights into the evolution and geographical diversity of Chinese lineage 1 PRRSV. These results will facilitate the development of programmes for the control and prevention of the emerging lineage 1 viruses in China.


Asunto(s)
Variación Genética , Sistemas de Lectura Abierta , Síndrome Respiratorio y de la Reproducción Porcina/epidemiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Animales , China/epidemiología , Filogenia , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Sus scrofa , Porcinos
15.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(10): 917-9, 2009 Oct.
Artículo en Zh | MEDLINE | ID: mdl-20137544

RESUMEN

OBJECTIVE: To observe the operative efficacy of patients with complete atrioventricular septal defect (CAVSD). METHODS: From January 2003 to June 2006, CAVSD patients underwent operative closure were included in this study. Color Doppler with apical four-chamber view was used to evaluate the degree of valve insufficiency before surgery and 2 days, 1 month, 6 months and 1 year after the surgery. Cardiac catheterization was performed to evaluate pulmonary artery pressure and pulmonary arteriolar resistance (PAR) before surgery in patients whose age were over 6 months. The time of staying at ICU, ventilation time after surgery and the occurrence of pulmonary artery hypertension crisis were recorded. RESULTS: 105 CAVSD patients underwent operative closure were enrolled in this study. The mean staying time at ICU was (4.7 +/- 2.4) days, and the mean ventilation time was (1.7 +/- 1.0)days, 9 patients (8.5%) developed pulmonary artery hypertension crisis after surgery. Patients with PAR > 8 Wood unit were older, staying time at ICU and ventilation time were longer compared patients with PAR < 8 Wood unit (all P < 0.05). The incidence of pulmonary artery hypertension crisis after surgery was also significantly higher in patients with PAR > 8 Wood unit compared patients with PAR < 8 Wood unit (P < 0.05). Hospital mortality was 3.8% (4/105). Three out of 4 hospital-dead patients had severe hypoplasia of the atrioventricular valve. Compared with preoperative, degree of valve insufficiency in both sides were relieved after surgery (P < 0.05). The valve insufficiency remained unchanged in 81 patients (77.1%), worsened in 14 patients (13.3%) and improved in 10 patients (9.6%) after surgery. CONCLUSIONS: Our results suggested that early surgical repair for CAVSD was safe and beneficial. Preoperative PAR > 8 Wood unit was associated with increased risk of pulmonary artery hypertension crisis after surgery in patients with CAVSD.


Asunto(s)
Defectos de los Tabiques Cardíacos/cirugía , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Resultado del Tratamiento
16.
Nanoscale ; 11(17): 8270-8280, 2019 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-30976761

RESUMEN

Although transition metal oxide-carbon (TMO-C) composites exhibit high Li storage capacity, the weak bonding between TMO particles and carbon mainly via van der Waals' force and the limited internal void space result in poor rate capability and cycling performance. Herein, MnO@graphene nanopeapods are produced by calcination of hydrothermally-synthesized MnO2-C composites. The flexible graphene shells provide superior conductivity and excellent structural stability to the MnO cores, and the enough internal void space can significantly buffer the drastic volume expansion. The MnO@graphene nanopeapods exhibit high Li storage capacity (1168 mA h g-1 at 50 mA g-1 and 945 mA h g-1 at 500 mA g-1) at a voltage platform of ∼1.2 V, excellent rate capability (728 mA h g-1 at 1000 mA g-1 and 505 mA h g-1 at 3000 mA g-1), high initial coulombic efficiency (85.9%) and remarkable long-life cycling performance (undiminished after 1000 cycles). The MnO@graphene nanopeapods have been successfully used as the anode to assemble a full battery with LiFePO4 as the cathode. Our results provide a useful and rational strategy to design high performance graphene-supported MnO composites for Li ion batteries.

17.
Transbound Emerg Dis ; 66(5): 2152-2162, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31207068

RESUMEN

Novel highly pathogenic porcine reproductive and respiratory syndrome viruses (PRRSVs) have attracted increasing attention owing to their continual high emergence and recent re-emergence. Recently, lineage 3 PRRSVs, belonging to the type 2 viruses, with novel characteristics and increased virulence have been continuously re-emerging in China, thereby posing a great threat to pig farming. However, available information about lineage 3 is limited. Here, we carried out molecular epidemiological investigations for PRRSV surveillance in most regions of China from 2007 to 2017. More than 3,000 samples were obtained, amounting to 73 sequences of lineage 3 viruses. The origin, demographic history and spread pattern of lineage 3 PRRSVs were investigated combining with the database globally. Phylogeography and phylodynamic analyses within a Bayesian statistical framework revealed that lineage 3 viruses originated in Taiwan. Followed by subsequent propagation to different areas and geography, it dichotomized into two endemic clusters. South China has become an epicentre for these viruses, which diffused into China's interiors in recent years. Furthermore, viral dispersal route analysis revealed the risk of viral diffusion. Overall, the origin, epidemic history and geographical evolution of lineage 3 PRRSVs were comprehensively analysed in this study. In particular, the epicentre of southern China and the diffusion routines of the viruses are highlighted in this study, and the possible continuous transmission of the novel lineages poses the biggest threat to pig farmers.


Asunto(s)
Brotes de Enfermedades/veterinaria , Síndrome Respiratorio y de la Reproducción Porcina/epidemiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Animales , China/epidemiología , Epidemiología Molecular , Filogeografía , Sus scrofa , Porcinos
18.
ChemSusChem ; 12(18): 4249-4256, 2019 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-31321901

RESUMEN

Nest-like porous graphene microspheres (NPGMs) are grown by using a chemical vapor deposition (CVD) method in a fluidized bed reactor from methane and basic magnesium carbonate microspheres (synthesized by a stirring-induced crystallization approach) as carbon source and template, respectively. The CVD-derived NPGMs have a few-layer structure and high electrical conductivity, as well as a three-dimensional individual macroarchitecture accompanied with well-developed pore channels and great structural integrity. As the electrode for a symmetric supercapacitor, the effect of different mass loadings for NPGMs-based electrodes on the capacitive energy-storage performance is investigated. Superior electrochemical properties with respect to gravimetric, areal, and total capacitances, rate capability, and durability are shown by the NPGMs-based symmetric supercapacitors, even at mass loadings up to 10 mg cm-2 . Moreover, the electrochemical behavior of the NPGMs-based electrode is much superior to those of two-dimensional lamella-like graphene and commercial activated carbon.

19.
Transbound Emerg Dis ; 66(1): 578-587, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30414310

RESUMEN

Lineage 3 of porcine reproductive and respiratory syndrome viruses, which belong to North America type 2, has a long epidemic history in China. The novel lineage 3 viruses constantly emerging in recent years are characterized by a high detection rate and significant pathogenicity. In this study, we investigated the prevalence of lineage 3 in southern China and selected two isolated strains for genome and virulence analyses. A cross-sectional epidemiology investigation indicated that the prevalence of lineage 3 antigens was 35.68% (95% CI: 27.6-44.3%) among 227 samples collected from over 100 infected farms from January 2016 to July 2017 in southern China. Two novel isolates of lineage 3 were selected. After 20 passages, Marc-145 cells were not susceptible to those viruses. Full-length genome analysis indicated that the two strains share 95.2% homology with each other and 95.7%-96.2% with highly pathogenic porcine reproductive and respiratory syndrome viruses (HP-PRRSVs; JXA1-like strain, lineage 8.7). Phylogenetic and molecular evolutionary results showed that for the two isolates, HP-PRRSV provides most of the ORF1 gene. Animal experiment revealed discrepancies in virulence between the strains. Although challenge resulted in 100% morbidity, the isolate carrying most of the HP-PRRSV ORF1 caused severe clinical symptoms and 40% mortality, whereas the other isolate containing part of the ORF1 gene caused no mortality. Overall, these findings suggest that lineage 3 viruses might be commonly circulating in most of southern China. Frequent recombination events within HP-PRRSVs of this lineage with changing virulence could represent potential threats to the pig industry.


Asunto(s)
Enfermedades Transmisibles Emergentes/veterinaria , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/aislamiento & purificación , Recombinación Genética , Enfermedades de los Porcinos/virología , Animales , China/epidemiología , Estudios Transversales , Evolución Molecular , Granjas , Técnica del Anticuerpo Fluorescente Indirecta/veterinaria , Filogenia , Síndrome Respiratorio y de la Reproducción Porcina/epidemiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/patogenicidad , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Porcinos , Enfermedades de los Porcinos/epidemiología , Virulencia/fisiología
20.
Vet Microbiol ; 231: 226-231, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30955814

RESUMEN

The porcine respiratory and reproductive syndrome virus (PRRSV) nucleocapsid (N) protein is a multiphosphorylated protein.It has been proved that the phosphorylation of N protein could regulate the growth ability of PRRSV in Marc-145 cells. However, further investigation is needed to determine whether phosphorylation of the N protein could affect PRRSV virulence in piglets. In this study, we confirmed that the mutations could impair PRRSV replication ability in porcine primary macrophages (PAMs) as they did in Marc-145 cells. The animal experiments suggested that the pathogenicity of the mutated virus (A105-120) was significantly reduced compared with parent strain (XH-GD). Our results suggested that the phosphorylation of the N protein contributes to virus replication and virulence. This study is the first to identify a specific modification involved in PRRSV pathogenicity. Mutation of PTMs sites is also a novel way to attenuate PRRSV virulence. The mutations could be a marker in a vaccine. In conclusion, our study will improve our understanding of the molecular mechanisms of PRRSV pathogenicity.


Asunto(s)
Mutación , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/patogenicidad , Virulencia/genética , Animales , Línea Celular , Replicación del ADN , Proteínas de la Nucleocápside/química , Fosforilación , Síndrome Respiratorio y de la Reproducción Porcina/patología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , ARN Viral/genética , Porcinos , Replicación Viral
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