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In 2020-21, during the COVID-19 pandemic, a free influenza vaccination program was initiated among the elderly residents in Ningbo, China. The impact of the COVID-19 pandemic and free vaccination policy on influenza vaccine uptake needs to be evaluated. The influenza vaccine uptake among individuals born before 31 December, 1962 from 2017-18 to 2022-23 season in Ningbo was analyzed. Multivariate logistic regressions were used to estimate the impact of the COVID-19 pandemic and free vaccination policy. Our analysis included an average of 1,856,565 individuals each year. Influenza vaccination coverage increased from 1.14% in 2017-18 to 33.41% in 2022-23. The vaccination coverage among the free policy target population was 50.03% in 2022-23. Multivariate analysis showed that free vaccination policy increased influenza vaccine uptake most (OR = 11.99, 95%CI: 11.87-12.11). The initial phase of the pandemic was associated with a positive effect on influenza vaccination (OR = 2.09, 95%CI: 2.07-2.12), but followed by a negative effect in the subsequent two seasons(2021-22: OR = 0.75, 95%CI: 0.73-0.76; 2022-23: OR = 0.40, 95%CI: 0.39-0.40). COVID-19 vaccination in the current season was a positive predictor of influenza vaccine uptake while not completing booster COVID-19 vaccination before was negative predictor in 2022-23. Having influenza vaccine history and having ILI medical history during the last season were also positive predictors of influenza vaccine uptake. Free vaccination policies have enhanced influenza vaccination coverage among elderly population. The COVID-19 pandemic plays different roles in different seasons. Our study highlights the need for how to implement free vaccination policies targeting vulnerable groups with low vaccination coverage.
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COVID-19 , Vacunas contra la Influenza , Gripe Humana , Cobertura de Vacunación , Humanos , China/epidemiología , Vacunas contra la Influenza/administración & dosificación , COVID-19/prevención & control , COVID-19/epidemiología , Anciano , Gripe Humana/prevención & control , Cobertura de Vacunación/estadística & datos numéricos , Masculino , Femenino , Anciano de 80 o más Años , Vacunación/estadística & datos numéricos , Programas de Inmunización/estadística & datos numéricos , Estaciones del Año , Política de Salud , Pandemias/prevención & control , Persona de Mediana EdadRESUMEN
BACKGROUND: Healthcare professionals' misjudgment of contraindications to vaccination can lead to unnecessary delays or missed vaccinations. It is essential to evaluate the knowledge and attitudes of healthcare professionals towards this issue. METHODS: A two-phase cross-sectional study was conducted among healthcare professionals in vaccination clinics in Ningbo in 2022. The study data were collected using questionnaires evaluating the knowledge and attitudes of contraindications and precautions to vaccination. Knowledge scores were calculated and a cutoff of 75 was defined for adequate knowledge scores. RESULTS: A total of 761 participants completed the questionnaire on attitudes. The majority of participants (86.20%) considered screening for vaccination contraindications to be the most important aspect of the vaccination administration process. A higher level of work stress was observed among full-time personnel engaged in this work. A total of 301 participants completed the questionnaire on relevant knowledge and practical experience. The median (IQR) total score was 75.00 (21.88). The lowest median score was observed for questions pertaining to disease diagnosis and classification (median: 40.00; IQR: 40.00). Regarding knowledge about vaccination contraindications, the scores for questions regarding national guidelines or vaccine package inserts (median: 85.71; IQR: 14.29) and guidelines from the WHO or ACIP (median: 100.00; IQR: 0.00) were higher than those derived from expert consensuses or literature findings (median: 71.43; IQR: 28.57) (p < 0.001). Higher scores were observed in the age group of 50-59 years, which included those who had received training twice or more times and those with relevant work experience. CONCLUSIONS: The knowledge of healthcare professionals working in vaccination clinics related to contraindications and precautions to vaccination is not sufficient, particularly regarding disease diagnosis and classification. Knowledge enhancement through repetitive skill training is required.
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BACKGROUND: Evidence on the effectiveness of influenza vaccination in the elderly is limited, and results are controversial. There are also few reports from China. METHODS: We conducted a test-negative case-control study design to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated visits among elderly (aged ≥ 60 years) across four influenza seasons in Ningbo, China, from 2018 to 19 to 2021-22. Influenza-positive cases and negative controls were randomly matched in a 1:1 ratio according to age, sex, hospital, and date of influenza testing. We used logistic regression models to compare vaccination odds ratios (ORs) in cases to controls. We calculated the VE as [100% × (1-adjusted OR)] and calculated the 95% confidence interval (CI) around the estimate. RESULTS: A total of 30,630 elderly patients tested for influenza with virus nucleic acid or antigen during the study period. After exclusions, we included 1 825 influenza-positive cases and 1 825 influenza-negative controls. Overall, the adjusted VE for influenza-related visits was 63.5% (95% CI, 56.3-69.5%), but varied by season. Influenza VE was 59.8% (95% CI, 51.5-66.7%) for influenza A and 89.6% (95% CI, 77.1-95.3%) for influenza B. The VE for ages 60-69 and 70-79 was 65.2% (95% CI, 55.4-72.9%) and 69.8% (95% CI, 58.7-77.9%), respectively, but only 45.4% (95% CI, 6.2-68.2%) for ages 80 and over. CONCLUSIONS: Standard-dose inactivated influenza vaccine has shown good protection in the elderly in China. However, protection may not be satisfactory in people aged 80 years and older.
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Vacunas contra la Influenza , Gripe Humana , Eficacia de las Vacunas , Vacunas de Productos Inactivados , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Gripe Humana/diagnóstico , Anciano , Masculino , Femenino , China/epidemiología , Estudios de Casos y Controles , Vacunas de Productos Inactivados/administración & dosificación , Persona de Mediana Edad , Anciano de 80 o más Años , Pueblos del Este de AsiaRESUMEN
BACKGROUND: The impact of repeated influenza vaccination on vaccine effectiveness has been a topic of debate. Conducting more multinational, multicenter studies in different influenza seasons is crucial for a better understanding of this issue. There is a lack of comprehensive related research reports in China. METHODS: Using the Regional Health Information Platform, we conducted a test-negative case-control study to evaluate the impact of repeated vaccination on the prevention of laboratory-confirmed influenza in individuals aged 60 and above in Ningbo during four influenza seasons from 2018-19 to 2021-22. Influenza-positive cases and negative controls were matched in a 1:1 ratio based on the visiting hospital and the date of influenza testing. Propensity score adjustment and multivariable logistic regression were used to estimate risk and address confounding effects. RESULTS: During the study period, a total of 30,630 elderly patients underwent influenza virus nucleic acid or antigen testing. After exclusions, we included 1976 cases of influenza-positive and 1976 cases of influenza-negative controls. Multivariable logistic regression analysis revealed that individuals receiving the vaccine in two consecutive seasons did not exhibit a significantly increased risk of influenza illness compared to those receiving the vaccine only in the current season (adjusted odds ratio: 1.22, 95% confidence interval: 0.94-1.58). However, the risk of influenza illness was found to be elevated in individuals who received the vaccine only in the previous season (adjusted odds ratio: 1.56, 95% confidence interval: 1.15-2.10) and even further elevated in those who had not received the vaccine in either of the consecutive two seasons (adjusted odds ratio: 3.39, 95% confidence interval: 2.80-4.09). CONCLUSIONS: Regardless of the vaccination history in the previous season, receiving the current season influenza vaccine is the best choice for the elderly population. Our study supports the initiative to vaccinate elderly individuals against influenza annually.
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Vacunas contra la Influenza , Gripe Humana , Vacunación , Eficacia de las Vacunas , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Gripe Humana/inmunología , Anciano , Estudios de Casos y Controles , Femenino , Masculino , China/epidemiología , Persona de Mediana Edad , Estaciones del Año , Anciano de 80 o más Años , Modelos LogísticosRESUMEN
Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, whereas IUGR with delayed growth in early postnatal life results in long-term brain deficits. In the present study, it was hypothesized that IUGR with early moderate catch-up growth may alleviate pulmonary vascular remodeling in adulthood without affecting memory function. An IUGR model was established by restricting maternal nutrition during pregnancy. Different growth patterns were achieved by adjusting the litter size in each group during lactation. Rats meeting the weight requirement at weaning were selected for subsequent studies at three time points (3, 9 and 13 weeks). Cognitive function was evaluated using a Y-maze. Invasive hemodynamic measurements were conducted to measure the mean pulmonary arterial pressure (mPAP). In addition, primary pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were cultured to investigate their role in the increase in mPAP following rapid catch-up growth. The results showed that memory function deficits in the rats in the delayed growth group were associated with reduced proliferation of neural stem cells in the subgranular zone of the hippocampus. Furthermore, moderate catch-up growth at the three time points improved memory function while maintaining a normal mPAP. In adult IUGR rats experiencing rapid catch-up growth, although memory function improved, elevated mPAP and medial thickening of pulmonary arterioles were observed. Additionally, PASMCs exhibited excessive proliferation, migration and anti-apoptotic activity in the rapid catch-up group, and PVECs also displayed excessive proliferation. These results suggested that moderate catch-up growth after IUGR is a better strategy for optimal cognition and cardiovascular health in adulthood compared with rapid catch-up growth or delayed growth.
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Kiwifruit ripening and senescence after harvesting are closely related to its economic value. Transcriptome analysis and biochemical parameters were used to investigate the differences in gene expression levels and the potential regulation of cell wall metabolism in kiwifruit treated with ozone, thereby regulating fruit softening and prolonging postharvest life. Compared to the control group, the activities of the cell wall modification enzyme were lower under ozone treatment, the content of polysaccharide in the cell wall of primary pectin and cellulose was higher, and the content of soluble pectin was lower. Meanwhile, ozone treatment delayed the degradation of the cell wall mesosphere during storage. A total of 20 pectinesterase (PE)-related genes were identified by sequencing analysis. The data analysis and quantitative polymerase chain reaction results confirmed that cell wall modifying enzyme genes played an important role in softening and senescence after harvesting, which may reduce or induce the expression of certain genes affecting cell wall metabolism. Ozone treatment not only regulates active genes such as xyloglucan endo glycosyltransferase/hydrolase, cellulose synthase, polygalacturonase, and PE to maintain the quality of fruit after harvest but also acts synergically with cell wall modifying enzymes to inhibit the degradation of cell wall, resulting in changes in the ultrastructure of cell wall, thereby reducing the hardness of kiwifruit. In addition, according to the results of cis-acting elements, cell wall degradation is also related to downstream hormone signaling, especially PE-related genes. These results provide a theoretical basis for studying the mechanism of firmness and cell wall metabolism difference of kiwifruit and also lay a good foundation for further research.
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Actinidia , Ozono , Humanos , Ozono/farmacología , Retraso del Tratamiento , Perfilación de la Expresión Génica , Pectinas/metabolismo , Actinidia/química , Pared Celular , Frutas/químicaRESUMEN
Newborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. Although there is increasing evidence suggesting that pericytes play a role in regulating myofibroblast transdifferentiation and angiogenesis in malignant and cardiovascular diseases, their involvement in the pathogenesis of IUGR-related pulmonary hypertension and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted using a Sprague-Dawley rat model of IUGR-related pulmonary hypertension. Our investigation revealed increased proliferation and migration of pulmonary microvascular pericytes in IUGR-related pulmonary hypertension, accompanied by weakened endothelial-pericyte interactions. Through whole-transcriptome sequencing, Ddx5 (DEAD-box protein 5) was identified as one of the hub genes in pericytes. DDX5, a member of the RNA helicase family, plays a role in the regulation of ATP-dependent RNA helicase activities and cellular function. MicroRNAs have been implicated in the pathogenesis of PAH, and microRNA-205 (miR-205) regulates cell proliferation, migration, and angiogenesis. The results of dual-luciferase reporter assays confirmed the specific binding of miR-205 to Ddx5. Mechanistically, miR-205 negatively regulates Ddx5, leading to the degradation of ß-catenin by inhibiting the phosphorylation of Gsk3ß at serine 9. In vitro experiments showed the addition of miR-205 effectively ameliorated pericyte dysfunction. Furthermore, in vivo experiments demonstrated that miR-205 agomir could ameliorate pulmonary hypertension. Our findings indicated that the downregulation of miR-205 expression mediates pericyte dysfunction through the activation of Ddx5. Therefore, targeting the miR-205/Ddx5/p-Gsk3ß/ß-catenin axis could be a promising therapeutic approach for IUGR-related pulmonary hypertension.
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Proliferación Celular , ARN Helicasas DEAD-box , Epigénesis Genética , Retardo del Crecimiento Fetal , Glucógeno Sintasa Quinasa 3 beta , Hipertensión Pulmonar , MicroARNs , Pericitos , Ratas Sprague-Dawley , Animales , Femenino , Humanos , Masculino , Ratas , beta Catenina/metabolismo , beta Catenina/genética , Movimiento Celular/genética , ARN Helicasas DEAD-box/metabolismo , ARN Helicasas DEAD-box/genética , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/genética , Retardo del Crecimiento Fetal/patología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , MicroARNs/genética , MicroARNs/metabolismo , Pericitos/metabolismo , Pericitos/patologíaRESUMEN
Owing to its easy decomposition and residue-free properties, ozone has been used as an effective and environmentally friendly physical preservation method for maintaining the post-harvest quality of fruits. This study aimed to investigate the effects of ozone treatment on the levels of oxidative stress markers and the status of the antioxidant defense system in refrigerated kiwifruit. Additionally, the study aimed to identify the differences in gene expression levels and potential regulatory effects from the transcriptional level. The results showed that ozone treatment reduced the respiration rate, maintained the fruit hardness and storage quality, and inhibited the ripening and senescence of kiwifruit. Ozone treatment activated antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) and ascorbate-glutathione cycle to prevent the increase of reactive oxygen species levels (H2O2, O2-â¢) and malonaldehyde content, maintaining lower membrane lipid peroxidation and reactive oxygen species (ROS) accumulation than the control treatment. Further analysis showed that the regulatory ability of ROS in kiwifruit treated with ozone was not only related to the synergistic effect of enzyme activity and gene expression related to the antioxidant oxidase system and the ascorbate-glutathione (ASA-GSH) cycle but also related to downstream hormone signaling. This study provides a foundation for understanding the potential effects of ozone treatment on the antioxidant cycle of kiwifruit and provides valuable insights into the molecular basis and related key genes involved in regulating ROS to delay aging in kiwifruit.
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Antioxidantes , Ozono , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ozono/farmacología , Ozono/metabolismo , Frutas/metabolismo , Peróxido de Hidrógeno/metabolismo , Transcriptoma , Catalasa/metabolismo , Superóxido Dismutasa/metabolismo , Glutatión/metabolismoRESUMEN
Anthocyanin is the main component of pigment in red-fleshed kiwifruit. 'Jinhongguan' is a new cultivar of Actinidia arguta with red peel and flesh after harvest. However, the specific types of anthocyanin in the 'Jinhongguan' fruit and its biosynthesis pathways remain largely unknown. Here, the total anthocyanin content in the fruit color conversion process was determined. The results showed that total anthocyanin content increased with the deepening color of the peel and flesh. To identify the genes related to anthocyanin biosynthesis and the types of anthocyanins in the 'Jinhongguan' fruit, a combined analysis of transcriptome and anthocyanin-targeted metabolome was carried out. A total of 5751 common differentially expressed genes (DEGs) at different stages of peel and flesh were identified, of which 2767 were common up-DEGs and 2976 were common down-DEGs. KEGG and GO enrichment analyses showed that the common up-DEGs were significantly enriched in anthocyanin synthesis-related pathways, suggesting some up-DEGs are involved in anthocyanin biosynthesis. In total, 29 metabolites were detected in the flesh by anthocyanin-targeted metabolome. Among these, nine were differential accumulation metabolites (DAMs) in comparison to red flesh vs green flesh. Six DAMs were up-regulated, with five of them were cyanidins. The content of cyanidin-3-O-galactoside was much higher than that of other DAMs, making it the main pigment in 'Jinhongguan'. Moreover, a total of 36 anthocyanin synthesis-related structural genes, 27 MYB transcription factors (TFs), 37 bHLH TFs and 9 WDR TFs were screened from the common DEGs. Correlation analysis of transcriptome and metabolome revealed that 9 structural genes, 6 MYB TFs, 6 bHLH TFs and 1 WDR TF were significantly associated with cyanidin-3-O-galactoside. Further, qRT-PCR analysis demonstrated that structural genes (AaPAL3, Aa4CL3, AaCHS2/3/8/9/11, AaDFR1/2, AaANR1, UFGT3a and UFGT6b) and TFs (MYB108, bHLH30, bHLH94-1 and WD43) play important roles in cyanidin biosynthesis. Overall, this study identified cyanidin-3-O-galactoside as the main anthocyanin type and revealed key candidate genes of red coloration of post-harvest fruit in Actinidia arguta. These findings provided new insights into the color formation mechanism of post-harvest fruit and offered a theoretical basis for color regulation in kiwifruit.
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Background: Concern about the risk of peripheral facial palsy (PFP) following vaccination is one reason for hesitancy in influenza vaccination. However, the association between the flu vaccine and PFP is still controversial, and further evidence is urgently needed. Methods: This self-controlled case series study evaluated PFP risk following inactivated influenza vaccine in the elderly using a large linked database in Ningbo, China. Relative incidence ratios (RIRs) and 95% confidence intervals (CIs) estimated using conditional Poisson regression were utilized to determine whether the risk of PFP was increased after vaccination. Results: This study included 467 episodes, which occurred in 244 females and 220 males. One hundred twenty-four episodes happened within 1-91 days after vaccination, accounting for 26.7%. The adjusted RIRs within 1-30 days, 31-60 days, 61-91 days, and 1-91 days after influenza vaccination were 0.95 (95% CI 0.69-1.30), 1.08 (95% CI 0.78-1.49), 1.01 (95% CI 0.70-1.45), and 1.00 (95% CI 0.81-1.24), respectively. Similar results were found in subgroup analyses and sensitivity analyses. Conclusions: Influenza vaccination does not increase PFP risk in the elderly population. This finding provides evidence to overcome concerns about facial paralysis after influenza vaccination.
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Parálisis Facial , Vacunas contra la Influenza , Gripe Humana , Masculino , Femenino , Humanos , Anciano , Parálisis Facial/epidemiología , Parálisis Facial/etiología , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pueblos del Este de Asia , Vacunas contra la Influenza/efectos adversos , Vacunación/efectos adversos , Vacunas de Productos Inactivados/efectos adversosRESUMEN
Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription factor FD is a key component of the florigen activation complex (FAC) which is composed of FLOWERING LOCUS T (FT), FD, and 14-3-3 proteins. In this study, isolation and characterization of CiFD in citrus found that there was alternative splicing (AS) of CiFD, forming two different proteins (CiFDα and CiFDß). Further investigation found that their expression patterns were similar in different tissues of citrus, but the subcellular localization and transcriptional activity were different. Overexpression of the CiFD DNA sequence (CiFD-DNA), CiFDα, or CiFDß in tobacco and citrus showed early flowering, and CiFD-DNA transgenic plants were the earliest, followed by CiFDß and CiFDα. Interestingly, CiFDα and CiFDß were induced by low temperature and drought, respectively. Further analysis showed that CiFDα can form a FAC complex with CiFT, Ci14-3-3, and then bind to the citrus APETALA1 (CiAP1) promoter and promote its expression. However, CiFDß can directly bind to the CiAP1 promoter independently of CiFT and Ci14-3-3. These results showed that CiFDß can form a more direct and simplified pathway that is independent of the FAC complex to regulate drought-induced flowering through AS. In addition, a bHLH transcription factor (CibHLH96) binds to CiFD promoter and promotes the expression of CiFD under drought condition. Transgenic analysis found that CibHLH96 can promote flowering in transgenic tobacco. These results suggest that CiFD is involved in drought- and low-temperature-induced citrus flowering through different regulatory patterns.
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Citrus , Citrus/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Proteínas de Plantas/metabolismo , Empalme Alternativo , Flores/fisiología , Sequías , Temperatura , Florigena/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismoRESUMEN
Objective@# To investigate the coverage of enterovirus 71 (EV71) vaccine among children born between 2018 and 2021 in Ningbo City, Zhejiang Province, so as to provide insights into formulating EV71 vaccination strategy.@*Methods@#Data pertaining to demography and EV71 vaccination among children born between 2018 and 2021 in Ningbo City were obtained from the Zhejiang Immunization Information Management System, and the coverage of vaccination, full-dose vaccination and timely vaccination of EV71 vaccine were analyzed. @*Results@#Totally 416 176 children were born between 2018 and 2021, including 216 977 boys (52.14%) and 199 199 girls (47.86%). The coverage rates of vaccination, full-dose vaccination and timely vaccination was 61.50%, 58.70% and 32.53%, respectively. The coverage rates of vaccination, full-dose vaccination and timely vaccination among local children (71.43%, 70.04% and 40.24%) were higher than those among migrant children (54.05%, 50.18% and 26.73%; P<0.05). The coverage rates of vaccination, full-dose vaccination and timely vaccination among urban children (67.72%, 65.06% and 40.37%) were higher than those among rural children (54.11%, 51.14% and 23.21%; P<0.05). The coverage rates of vaccination were 54.98%, 61.24%, 65.10% and 66.72%, the coverage rates of full-dose vaccination were 52.16%, 58.72%, 62.44% and 63.39%, and the coverage rates of timely vaccination were 22.47%, 25.86%, 39.14% and 48.03% by the born year from 2018 to 2021, all showing increasing trends year by year (P<0.05). @*Conclusion@#The coverage of vaccination, full-dose vaccination and timely vaccination of EV71 vaccine appears a tendency towards a rise among the 2018-2021 birth cohorts in Ningbo City, while the coverage of timely vaccination need to be improved. Health education for EV71 vaccination should be enhanced for rural and migrant children.
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Kiwifruit (Actinidia chinensis Planch.) is a functionally dioecious plant, which displays diverse morphology in male and female flowers. MADS-box is an ancient and huge gene family that plays a key role in plant floral organ differentiation. In this study, we have identified 89 MADS-box genes from A. chinensis Red 5 genome. These genes are distributed on 26 chromosomes and are classified into type I (21 genes) and type II (68 genes). Overall, type II AcMADS-box genes have more complex structures than type I with more exons, protein domains, and motifs, indicating that type II genes may have more diverse functions. Gene duplication analysis showed that most collinearity occurred in type II AcMADS-box genes, which was consistent with a large number of type II genes. Analysis of cis-acting elements in promoters showed that AcMADS-box genes are mainly associated with light and phytohormone responsiveness. The expression profile of AcMADS-box genes in different tissues showed that most genes were highly expressed in flowers. Further, the qRT-PCR analysis of the floral organ ABCDE model-related genes in male and female flowers revealed that AcMADS4, AcMADS56, and AcMADS70 were significantly expressed in female flowers. It indicated that those genes may play an important role in the sex differentiation of kiwifruit. This work provided a comprehensive analysis of the AcMADS-box genes and may help facilitate our understanding of the sex differentiation regulatory mechanism in kiwifruit.
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Background Intrauterine growth restriction (IUGR) is closely related to systemic or pulmonary hypertension (PH) in adulthood. Aberrant crosstalk between pulmonary vascular endothelial cells (PVECs) and pulmonary arterial smooth muscle cells (PASMCs) that is mediated by exosomes plays an essential role in the progression of PH. FoxM1 (Forkhead box M1) is a key transcription factor that governs many important biological processes. Methods and Results IUGR-induced PH rat models were established. Transwell plates were used to coculture PVECs and PASMCs. Exosomes were isolated from PVEC-derived medium, and a microRNA (miRNA) screening was proceeded to identify effects of IUGR on small RNAs enclosed within exosomes. Dual-Luciferase assay was performed to validate the predicted binding sites of miRNAs on FoxM1 3' untranslated region. FoxM1 inhibitor thiostrepton was used in IUGR-induced PH rats. In this study, we found that FoxM1 expression was remarkably increased in IUGR-induced PH, and PASMCs were regulated by PVECs through FoxM1 signaling in a non-contact way. An miRNA screening showed that miR-214-3p, miR-326-3p, and miR-125b-2-3p were downregulated in PVEC-derived exosomes of the IUGR group, which were associated with overexpression of FoxM1 and more significant proliferation and migration of PASMCs. Dual-Luciferase assay demonstrated that the 3 miRNAs directly targeted FoxM1 3' untranslated region. FoxM1 inhibition blocked the PVECs-PASMCs crosstalk and reversed the abnormal functions of PASMCs. In vivo, treatment with thiostrepton significantly reduced the severity of PH. Conclusions Transmission of exosomal miRNAs from PVECs regulated the functions of PASMCs via FoxM1 signaling, and FoxM1 may serve as a potential therapeutic target in IUGR-induced PH.
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Hipertensión Pulmonar , MicroARNs , Animales , Femenino , Ratas , Regiones no Traducidas 3' , Movimiento Celular , Proliferación Celular/genética , Células Endoteliales/metabolismo , Retardo del Crecimiento Fetal , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Miocitos del Músculo Liso/metabolismo , Arteria Pulmonar , Tioestreptona/metabolismoRESUMEN
The long juvenile period of perennial woody plants is a major constraint in breeding programs. FLOWERING LOCUS T (FT) protein is an important mobile florigen signal that induces plant flowering. However, whether FT can be transported in woody plants to shorten the juvenile period is unknown, and its transport mechanism remains unclear. In this study, trifoliate orange FT (ToFT) and Arabidopsis FT (AtFT, which has been confirmed to be transportable in Arabidopsis) as a control were transformed into tomato and trifoliate orange, and early flowering was induced in the transgenic plants. Long-distance and two-way (upward and downward) transmission of ToFT and AtFT proteins was confirmed in both tomato and trifoliate orange using grafting and western blot analysis. However, rootstocks of transgenic trifoliate orange could not induce flowering in grafted wild-type juvenile scions because of the low accumulation of total FT protein in the grafted scions. It was further confirmed that endogenous ToFT protein was reduced in trifoliate orange, and the accumulation of the transported ToFT and AtFT proteins was lower than that in grafted juvenile tomato scions. Furthermore, the trifoliate orange FT-INTERACTING PROTEIN1 homolog (ToFTIP1) was isolated by yeast two-hybrid analysis. The FTIP1 homolog may regulate FT transport by interacting with FT in tomato and trifoliate orange. Our findings suggest that FT transport may be conserved between the tomato model and woody plants. However, in woody plants, the transported FT protein did not accumulate in significant amounts in the grafted wild-type juvenile scions and induce the scions to flower.
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PISTILLATA (PI), as a member of MADS-box transcription factor, plays an important role in petal and stamen specification in Arabidopsis. However, little is known about PI-like genes in citrus. To understand the molecular mechanism of PI during the developmental process of citrus flower, a PI-like gene CcMADS20 was isolated from Citrus Clemantina. Sequence alignment and phylogenetic analysis revealed that CcMADS20 had relatively high similarity with PI-like homolog and was classified in the core dicotyledonous group. The temporal and spatial expression analyses showed that CcMADS20 was specifically expressed in petal and stamen of citrus flower, which was consistent with PI expression pattern in Arabidopsis. Protein interaction revealed that CcMADS20 could form heterodimer with AP3-like proteins. Furthermore, ectopic overexpression of CcMADS20 in Arabidopsis resulted in transformation of sepals into petal-like structure, as observed in other plants overexpressing a functional PI-like homolog. Additionally, promoter fragments of CcMADS20 were also cloned in the representative 21 citrus varieties. Interestingly, four types of promoters were discovered in these citrus varieties, resulting from two stable insert/deletion fragments (Locus1 and Locus2). The homo/hetero-zygosity of promoter alleles in each variety was strongly related to the evolutionary origin of citrus. Four promoters activity analysis indicated that Locus1 presence inhibited CcMADS20 transcriptional activity and Locus2 presence promoted its transcriptional activity. These findings suggested that CcMADS20 determines petal and stamen development during the evolutionary process of citrus and four promoters discovered, as effective genetic markers, are valuable for citrus breeding practices.
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Arabidopsis , Citrus , Arabidopsis/metabolismo , Citrus/genética , Citrus/metabolismo , Proteínas de Dominio MADS/metabolismo , Filogenia , FitomejoramientoRESUMEN
MADS-box genes are involved in various developmental processes including vegetative development, flower architecture, flowering, pollen formation, seed and fruit development. However, the function of most MADS-box genes and their regulation mechanism are still unclear in woody plants compared with model plants. In this study, a MADS-box gene (CiMADS43) was identified in citrus. Phylogenetic and sequence analysis showed that CiMADS43 is a GOA-like Bsister MADS-box gene. It was localized in the nucleus and as a transcriptional activator. Overexpression of CiMADS43 promoted early flowering and leaves curling in transgenic Arabidopsis. Besides, overexpression or knockout of CiMADS43 also showed leaf curl phenotype in citrus similar to that of CiMADS43 overexpressed in Arabidopsis. Protein-protein interaction found that a SEPALLATA (SEP)-like protein (CiAGL9) interacted with CiMADS43 protein. Interestingly, CiAGL9 also can bind to the CiMADS43 promoter and promote its transcription. Expression analysis also showed that these two genes were closely related to seasonal flowering and the development of the leaf in citrus. Our findings revealed the multifunctional roles of CiMADS43 in the vegetative and reproductive development of citrus. These results will facilitate our understanding of the evolution and molecular mechanisms of MADS-box genes in citrus.
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Citrus/crecimiento & desarrollo , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Dominios y Motivos de Interacción de Proteínas , Secuencia de Aminoácidos , Citrus/genética , Citrus/metabolismo , Flores/genética , Flores/metabolismo , Proteínas de Dominio MADS/genética , Fenotipo , Filogenia , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Homología de SecuenciaRESUMEN
Shoot-tip abortion is a very common phenomenon in some perennial woody plants and it affects the height, architecture, and branch orientation of trees; however, little is currently known about the underlying mechanisms. In this study, we identified a gene in sweet orange (Citrus sinensis) encoding a KNAT-like protein (CsKN1) and found high expression in the shoot apical meristem (SAM). Overexpression of CsKN1 in transgenic plants prolonged the vegetative growth of SAMs, whilst silencing resulted in either the loss or inhibition of SAMs. Yeast two-hybrid analysis revealed that CsKN1 interacted with another citrus KNAT-like protein (CsKN2), and overexpression of CsKN2 in lemon and tobacco caused an extreme multiple-meristem phenotype. Overexpression of CsKN1 and CsKN2 in transgenic plants resulted in the differential expression of numerous genes related to hormone biosynthesis and signaling. Yeast one-hybrid analysis revealed that the CsKN1-CsKN2 complex can bind to the promoter of citrus floral meristem gene LEAFY (CsLFY) and inhibit its expression. These results indicated that CsKN1 might prolong the vegetative growth period of SAMs by delaying flowering. In addition, an ethylene-responsive factor (CsERF) was found to bind to the CsKN1 promoter and suppresses its transcription. Overexpression of CsERF in Arabidopsis increased the contents of ethylene and reactive oxygen species, which might induce the occurrence of shoot-tip abscission. On the basis of our results, we conclude that CsKN1 and CsKN2 might work cooperatively to regulate the shoot-tip abscission process in spring shoots of sweet orange.
Asunto(s)
Citrus sinensis , Citrus , Citrus/genética , Citrus/metabolismo , Citrus sinensis/genética , Citrus sinensis/metabolismo , Regulación de la Expresión Génica de las Plantas , Meristema/genética , Meristema/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
BACKGROUND: In China, enterovirus 71 (EV71) is the major etiological agents of hand foot mouth disease that poses severe risks to children's health. Since 2015, three inactivated EV71 vaccines have been approved for use. Previous studies indicated the high willingness of EV71 vaccination in eastern China. However, few studies have assessed coverage and utilization patterns of EV71 vaccine in China. METHODS: Children born during 2012-2018 were sampled and their records were abstracted from Ningbo childhood immunization information management system. Descriptive statistics characterized the study population and assessed coverage and timeliness for EV71 vaccination. Simultaneous administration patterns as well as type of EV71 vaccine used were also evaluated. Bivariate and multivariable analysis was used to examine the relationship of socio-demographic characteristics with vaccination coverage and timeliness. RESULTS: Of 716,178 children living in Ningbo. One hundred seventy-two thousand two hundred thirty-six received EV71 vaccine with a coverage rate of 24.05% and only 8.61% received vaccination timely. 21.97% of children received the complete two dose EV71 series but only 6.49% completed timely. Vaccination coverage and timeliness increased significantly from 2012 birth cohort to 2018 birth cohort. Relatively higher coverage and timeliness were observed in resident children, Inner districts, high socioeconomic areas and large-scaled immunization clinics. Of 329,569 doses of EV71 vaccine, only 5853(1.78%) doses were administered at the same day as other vaccines. CONCLUSIONS: There is a need for increasing EV71 vaccination coverage and timeliness as well as eliminating disparities among different populations. Our study highlights the importance of simultaneous administration to increasing coverage and timeliness of EV71 vaccination.
Asunto(s)
Enterovirus Humano A , Enterovirus , Vacunas Virales , Niño , China , Humanos , Lactante , Vacunación , Cobertura de VacunaciónRESUMEN
BACKGROUND: Health authorities recommend influenza vaccination to diabetic patients. Nevertheless, the vaccination coverage of adults was low in China. This study aimed to estimate influenza vaccination intentions and actual uptake among diabetic patients in China and identify the motivators and barriers associated with vaccination. METHODS: During Nov 2016-Jan 2017, 1960 diabetic patients were invited to participate in the investigation about influenza vaccination based on health belief model (HBM). To link vaccination intention to behavior, a follow-up survey was conducted to collect vaccination records of the 2016-2017 season. Predictors of the motivation to obtain influenza vaccination were assessed using logistic regressions. RESULTS: 1914 diabetic patients completed the survey. 46.13% participants reported intentions to be vaccinated against influenza and 7.84% actually received vaccination. In the multivariate models, while all the domains of HBM constructs were associated with intentions, age, increasing numbers of comorbidity, urban residents, perceived susceptibility, perceived benefits, free vaccination, and vaccination history displayed positive associations with vaccine uptake while increasing income and perceptions of barriers were negative predictors of vaccine uptake. Besides, interactions between perceived susceptibility and healthcare workers' (HCW's) recommendation, perceived severity and benefits, perceived severity and health-seeking behaviors, perceived benefits, and influence of family/friends had a significant positive effect modification on the vaccine uptake. CONCLUSION: To improve diabetic patients' influenza vaccination and close the intention-behavior gap, multipronged strategies are required not only to increase vaccination intention by promoting HCW's recommendation to improve perceptions about influenza vaccination but also facilitate a follow through on initial intentions by implementing free influenza vaccination program funded by the government.