RESUMEN
Differentiation syndrome (DS) is the second leading cause of death in acute promyelocytic leukaemia (APL) patients. Few studies have tested predictors of DS events. This study aimed to identify optimized predictors of DS events related to APL. The data of 298 consecutive patients who were newly diagnosed with APL between December 2012 and June 2023 were retrospectively investigated. A systematic review of computer-based patient medical records was conducted to obtain clinical data, including baseline characteristics, routine blood examination findings, biochemical indices and clinical manifestations of DS. Among the 298 patients, 158 were classified into the no-DS group, while 140 had DS. Compared with those of patients without DS, the peripheral blast count, age, and WBC count at each time point were significantly different in patients with DS (P < 0.05 for all time points). Generalized linear mixed models (GLMMs) revealed that WBC Double (Coeff. 0.442, P = 0.000) and WBCPeak (Coeff. 0.879, P = 0.000) were independent risk factors for DS. The frequencies of clinical manifestations of unexplained fever (P = 0.003), dyspnoea (P = 0.002), weight gain of more than 5 kg (P = 0.006), pleural effusion (P = 0.001), pulmonary infiltrates (P < 0.001), pericardial effusion (P = 0.002) and renal failure (P = 0.006) were considerably lower in moderate DS patients than in severe DS patients. The WBCDouble occurs earlier than the WBCpeak occurrence, so WBC Double might be a new indicator of DS.
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In winter-annual plants, exposure to cold temperatures induces cold tolerance and accelerates flowering in the following spring. However, little is known about plant adaptations to dehydration stress after winter. Here, we found that dehydration tolerance is reduced in winter-annual Arabidopsis (Arabidopsis thaliana) after vernalization. Winter-annual Arabidopsis plants with functional FRIGIDA (FRI) exhibited high dehydration tolerance, with small stomatal apertures and hypersensitivity to exogenous abscisic acid. Dehydration tolerance and FLOWERING LOCUS C (FLC) transcript levels gradually decreased with prolonged cold exposure in FRI plants. FLC directly bound to the promoter of OPEN STOMATA1 (OST1) and activated OST1 expression. Loss of FLC function resulted in decreased dehydration tolerance and reduced OST1 transcript levels. FLC and OST1 act in the same dehydration stress pathway, with OST1 acting downstream of FLC. Our study provides insights into the mechanisms by which FRI modulates dehydration tolerance through the FLC-OST1 module. Our results suggest that winter-annual Arabidopsis integrates dehydration tolerance and flowering time to adapt to environmental changes from winter to spring.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Deshidratación/metabolismo , Flores/genética , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Estaciones del AñoRESUMEN
Deposition of H2A.Z and H4 acetylation by SWI2/SNF2-Related 1 Chromatin Remodeling (SWR1) and Nucleosome Acetyltransferase of H4 (NuA4) complexes in specific regulatory regions modulates transcription and development. However, little is known about these complexes in Oryza sativa (rice) development. Here, we reported that OsYAF9 and OsSWC4, two subunits of SWR1 and NuA4 complexes, are involved in rice vegetative and reproductive development. Loss of OsYAF9 resulted in reduced height, fewer tillers, fewer pollen grains, and defects in embryogenesis and seed filling. OsYAF9 directly interacted with OsSWC4 in vitro and in vivo. Loss of OsSWC4 function exhibited defects in pollen germination and failure to generate seeds, whereas knockdown of OsSWC4 resulted in reduced height and fewer tillers. The reduced height caused by OsYAF9 mutation and OsSWC4 knockdown was due to shorter internodes and defects in cell elongation, and this phenotype was rescued with gibberellin (GA) treatment, suggesting that both OsYAF9 and OsSWC4 are involved in the GA biosynthesis pathway. OsSWC4 was directly bound to the AT-rich region of GA biosynthesis genes, which in turn accomplished H2A.Z deposition and H4 acetylation at the GA biosynthesis genes with OsYAF9. Together, our study provides insights into the mechanisms involving OsSWC4 and OsYAF9 forming a protein complex to promote rice internode elongation with H2A.Z deposition and H4 acetylation.
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Proteínas de Unión al ADN/metabolismo , Oryza , Proteínas de Plantas/metabolismo , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción/metabolismo , Acetilación , Cromatina/metabolismo , Ensamble y Desensamble de Cromatina , Proteínas de Unión al ADN/genética , Histonas/metabolismo , Nucleosomas/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Saccharomyces cerevisiae/genética , Factores de Transcripción/genéticaRESUMEN
Severe bleeding is the leading cause of early death in patients with newly diagnosed acute promyelocytic leukemia (APL). However, there are no means for hemorrhagic risk stratification in APL. This study aimed to identify optimized predictors of severe bleeding events related to APL. A total of 109 consecutive patients with newly diagnosed APL from January 2015 to April 2022 were retrospectively investigated. A systematic review of computer-based patient medical records was conducted to obtain clinical date, including baseline characteristics, routine blood examination findings, coagulation and fibrinolysis indexes, and bleeding events. Among the 109 patients, 89 were classified into the no-severe bleeding group, while 20 had severe bleeding. Compared with the patients with no severe bleeding, the patients with severe bleeding had significantly higher circulating leukemic cell percentages, disseminated intravascular coagulation (DIC) scores, D-dimer (D-D) levels, and fibrin degradation product (FDP) levels. They also had lower fibrinogen (FIB) levels and a longer prothrombin time. Multivariate analysis revealed that the circulating leukemic cell percentage (OR = 1.040, CI = 1.008-1.072, P = 0.012), FIB level (OR = 0.101, CI = 0.011-0.896, P = 0.040), and FDP level (OR = 1.012, CI = 1.000-1.024, P = 0.047) were independent risk factors for severe bleeding. FDP/FIB, D-D/FIB, and seven meaningful indicators in the single-factor analysis were included in the receiver operating characteristic (ROC) curve analysis. The results showed that FDP/FIB was the best indicator for predicting severe bleeding related to newly diagnosed APL. The area under the ROC curve of FDP/FIB was 0.915, and the best cutoff value was 61.77, with 100% sensitivity and 74.2% specificity. Statistical analysis showed a higher incidence of severe bleeding and higher DIC scores when FDP/FIB was >61.77 in APL patients. FDP/FIB has obvious advantages in predicting the degree of bleeding associated with primary promyelocytic leukemia; the greater the FDP/FIB value, the more severe the bleeding. The risk of severe bleeding was the highest when FDP/FIB > 61.77.
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Coagulación Intravascular Diseminada , Leucemia Promielocítica Aguda , Humanos , Coagulación Sanguínea , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/etiología , Hemorragia/etiología , Hemorragia/complicaciones , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/diagnóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite advances in immunotherapy and targeted treatments for malignancies of the central nervous system (CNS), the treatment of brain metastases (BMs) remains a formidable challenge, due largely to difficulties in crossing the blood-brain barrier (BBB), drug resistance, and molecular discrepancies. Focused ultrasound (FUS) is a non-invasive tool for BBB breaching, tumor ablation, enhancing drug delivery, promoting the release of tumor biomarkers for liquid biopsy, or the tumor microenvironment disruption. This paper presents a comprehensive review of the current literature related to FUS and its application in the treatment of brain metastasis. METHODS: This review of the current literature via PubMed, Google Scholar, and Clincaltrials.gov focused on clinical trials in which FUS is used in the intracranial treatment of metastatic tumor, glioma, or GBM. RESULTS: FUS is safe and effective for treatment of primary or metastatic brain tumors. FUS-augmented drug delivery can open BBB to facilitate the transport of chemotherapeutic agents, immunotherapies, and targeted treatments. The integration of FUS with liquid biopsy has considerable potential for early tumor detection, precise gene profiling, and personalized therapy. Sonodynamic therapy can induce tumor cell apoptosis and could potentially be used to enhance the outcomes of other tumor treatments, such as surgery and chemotherapy. CONCLUSION: Further work is required to establish FUS as a standard therapy for BMs. FUS has the potential to transform brain tumor treatment, particularly when combined with immunotherapy and targeted therapy as a non-invasive alternative to surgery and radiation therapy.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/patología , Barrera Hematoencefálica , Sistemas de Liberación de Medicamentos , Inmunoterapia , Encéfalo/patología , Microambiente TumoralRESUMEN
PURPOSE: Given the availability of TKIs with high central nervous system efficacy, the question arises as to whether upfront SRS provides additional clinical benefits. The goal of this study was to characterize the clinical outcomes of SRS as salvage therapy for TKI-uncontrolled BMs. METHODS: This retrospective study included EGFR-mutant NSCLC patients presenting BMs at the time of primary tumor diagnosis. BMs were categorized into three subgroups, referred to as "Nature of TKI-treated BMs", "TKI-controlled brain metastases ± SRS", and "SRS salvage therapy". The first subgroup analysis characterized the effects of TKIs on tumor behavior. In the second subgroup, we compared outcomes of TKI-controlled BMs treated with TKI alone versus those treated with combined TKI-SRS therapy. The third subgroup characterized the outcomes of TKI-uncontrolled BMs treated with SRS as salvage therapy Clinical outcomes include local and distant tumor control. RESULTS: This study included 106 patients with a total of 683 BMs. TKI treatment achieved control in 63% of local tumors at 24 months. Among the TKI-controlled BMs, local tumor control was significantly higher in the combined TKI-SRS group (93%) than in the TKI-alone group (65%) at 24 months (p < 0.001). No differences were observed between the two groups in terms of distant tumor control (p = 0.832). In dealing with TKI-uncontrolled BMs, salvage SRS achieved local tumor control in 58% of BMs at 24 months. CONCLUSIONS: While upfront TKI alone proved highly effective in BM control, this study also demonstrated the outcomes of SRS when implemented concurrently with TKI or as salvage therapy for TKI-uncontrolled BMs. This study also presents a strategy of the precise timing and targeting of SRS to lesions in progression.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Radiocirugia , Humanos , Estudios Retrospectivos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Receptores ErbB/genéticaRESUMEN
OBJECTIVE: To identify the association between the phosphorylated Janus kinase 2/phosphorylated signal transducer and activator of transcription (p-JAK2/p-STAT3) signaling pathway and follicular development in polycystic ovary syndrome (PCOS) rats, and explore the underlying mechanism. To evaluate the role of exogenous JAK2 inhibitor AG490 in the model and the associations among luteinizing hormone/choriogonadotropin receptor (LHCGR), follicle-stimulating hormone receptor (FSHR), cytochrome P450 17α (CYP17a), cytochrome P450 19 (CYP19), and PCOS. RESULTS: Rat models of PCOS was established. PCOS rats were intraperitoneally treated with double-distilled water (ddH2O)/DMSO/AG490. The rate of ovarian morphological recovery in the AG490 group was significantly higher compared with the DMSO group (83.3 % vs 9.1 %, X2 = 12.68, P < 0.001). Moreover, the short in the time the estrous cycle was resumed in the AG490 group (hazard ratio = 16.32, P < 0.001) compared with the DMSO group. Compared with the controls, p-JAK2, p-STAT3, LHCGR, and CYP17a expression levels were increased whereas that of FSHR and CYP19 were decreased in the ovaries of PCOS rats. However, an opposite trend was observed after treatment with AG490. Software prediction revealed that the p-STAT3 bound to the promoter regions of LHCGR, FSHR, CYP17a, and CYP19 genes. This finding was confirmed by results of correlation analysis (R = 0.834, -0.836, 0.875 and -0.712, respectively, all P < 0.001). CONCLUSION: This study demonstrated that the p-JAK2/p-STAT3 signaling pathway was involved in follicular development in PCOS rats by upregulating LHCGR and CYP17a expression, and downregulating that of FSHR and CYP19. AG490 treatment exerted beneficial effects. LHCGR, FSHR, CYP17a, and CYP19 are candidate genes associated with follicular development in PCOS rats.
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Janus Quinasa 2 , Síndrome del Ovario Poliquístico , Factor de Transcripción STAT3 , Animales , Femenino , Humanos , Ratas , Aromatasa/genética , Aromatasa/metabolismo , Dimetilsulfóxido/farmacología , Janus Quinasa 2/metabolismo , Síndrome del Ovario Poliquístico/inducido químicamente , Transducción de Señal , Factor de Transcripción STAT3/metabolismoRESUMEN
Maize leaf angle (LA) is a complex quantitative trait that is controlled by developmental signals, hormones, and environmental factors. However, the connection between histone methylation and LAs in maize remains unclear. Here, we reported that SET domain protein 128 (SDG128) is involved in leaf inclination in maize. Knockdown of SDG128 using an RNA interference approach resulted in an expanded architecture, less large vascular bundles, more small vascular bundles, and larger spacing of large vascular bundles in the auricles. SDG128 interacts with ZmGID2 both in vitro and in vivo. Knockdown of ZmGID2 also showed a larger LA with less large vascular bundles and larger spacing of vascular bundles. In addition, the transcription level of cell wall expansion family genes ZmEXPA1, ZmEXPB2, and GRMZM2G005887; transcriptional factor genes Lg1, ZmTAC1, and ZmCLA4; and auxin pathway genes ZmYUCCA7, ZmYUCCA8, and ZmARF22 was reduced in SDG128 and ZmGID2 knockdown plants. SDG128 directly targets ZmEXPA1, ZmEXPB2, LG1, and ZmTAC1 and is required for H3K4me3 deposition at these genes. Together, the results of the present study suggest that SDG128 and ZmGID2 are involved in the maize leaf inclination.
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Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Zea mays/fisiología , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Regulación de la Expresión Génica de las Plantas , Histonas , Ácidos Indolacéticos/metabolismo , Mutación , Hojas de la Planta/citología , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Interferencia de ARN , Zea mays/citologíaRESUMEN
BACKGROUND: Hypertension is highly prevalent and associated with the elevated risks of cardiovascular diseases, dementia, and physical disabilities among adults. Although the correlation between bilirubin and hypertension has been reported, the observation in quinquagenarian population is scarce. We aimed to examine bilirubin-hypertension association in Guankou Ageing Cohort Study. METHODS: Participants ≥ 55 years were recruited and their questionnaires and physical examination data were collected. Kaplan-Meier survival analysis and Cox proportional hazards regression were implemented to assess the hypertension risk. The non-liner dose-response relationships of bilirubin-hypertension were determined by restricted cubic spline (RCS) models. Receiver operating characteristic (ROC) curves and multiple factors analysis (MFA) were performed to evaluate the predictive abilities. RESULTS: 1881 eligible participants (male 43.75%, female 56.25%) with the median age of 61.00 (59.00-66.00) were included. The hazard ratio (HR, 95% CI) of serum total bilirubin (STB) and unconjugated bilirubin (UCB) were 1.03 (1.01-1.05) and 1.05 (1.03-1.07), while conjugated bilirubin (CB) showed a weak protective effect with the HR of 0.96 (0.92-0.99), and the associations remained significant in all models. RCS analyses further indicated the similar bidirectional effects of STB and UCB with the cut-off of 12.17 µmol/L and 8.59 µmol/L, while CB exhibited inverse bidirectional dose-response relationship with a cut-off of 3.47 µmol/L. ROC curves and MFA showed baseline STB combined with age, BMI, and waist circumference could well discriminate the low and high of hypertension risk. CONCLUSIONS: Our findings suggested the higher levels of total and unconjugated bilirubin were hazardous factors of hypertension, while an inverse effect presented when more bilirubin was conjugated.
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Bilirrubina , Hipertensión , Adulto , Envejecimiento , China/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Factores de RiesgoRESUMEN
AKT2 potassium (K+) channels are members of the plant Shaker family which mediate dual-directional K+ transport with weak voltage-dependency. Here we show that OsAKT2 of rice (Oryza sativa) functions mainly as an inward rectifier with strong voltage-dependency and acutely suppressed outward activity. This is attributed to the presence of a unique K191 residue in the S4 domain. The typical bi-directional leak-like property was restored by a single K191R mutation, indicating that this functional distinction is an intrinsic characteristic of OsAKT2. Furthermore, the opposite R195K mutation of AtAKT2 changed the channel to an inward-rectifier similar to OsAKT2. OsAKT2 was modulated by OsCBL1/OsCIPK23, evoking the outward activity and diminishing the inward current. The physiological relevance in relation to the rectification diversity of OsAKT2 was addressed by functional assembly in the Arabidopsis (Arabidopsis thaliana) akt2 mutant. Overexpression (OE) of OsAKT2 complemented the K+ deficiency in the phloem sap and leaves of the mutant plants but did not significantly contribute to the transport of sugars. However, the expression of OsAKT2-K191R overcame both the shortage of phloem K+ and sucrose of the akt2 mutant, which was comparable to the effects of the OE of AtAKT2, while the expression of the inward mutation AtAKT2-R195K resembled the effects of OsAKT2. Additionally, OE of OsAKT2 ameliorated the salt tolerance of Arabidopsis.
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Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Oryza/genética , Oryza/metabolismo , Floema/metabolismo , Canales de Potasio/metabolismo , Tolerancia a la Sal/fisiología , Productos Agrícolas/genética , Productos Agrícolas/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Mutación , Floema/genética , Canales de Potasio/genética , Tolerancia a la Sal/genéticaRESUMEN
BACKGROUND: There is still a relatively serious disease burden of infectious diseases and the warning time for different infectious diseases before implementation of interventions is important. The logistic differential equation models can be used for predicting early warning of infectious diseases. The aim of this study is to compare the disease fitting effects of the logistic differential equation (LDE) model and the generalized logistic differential equation (GLDE) model for the first time using data on multiple infectious diseases in Jilin Province and to calculate the early warning signals for different types of infectious diseases using these two models in Jilin Province to solve the disease early warning schedule for Jilin Province throughout the year. METHODS: Collecting the incidence of 22 infectious diseases in Jilin Province, China. The LDE and GLDE models were used to calculate the recommended warning week (RWW), the epidemic acceleration week (EAW) and warning removed week (WRW) for acute infectious diseases with seasonality, respectively. RESULTS: Five diseases were selected for analysis based on screening principles: hemorrhagic fever with renal syndrome (HFRS), shigellosis, mumps, Hand, foot and mouth disease (HFMD), and scarlet fever. The GLDE model fitted the above diseases better (0.80 ≤ R2 ≤ 0.94, P < 0. 005) than the LDE model. The estimated warning durations (per year) of the LDE model for the above diseases were: weeks 12-23 and 40-50; weeks 20-36; weeks 15-24 and 43-52; weeks 26-34; and weeks 16-25 and 41-50. While the durations of early warning (per year) estimated by the GLDE model were: weeks 7-24 and 36-51; weeks 13-37; weeks 11-26 and 39-54; weeks 23-35; and weeks 12-26 and 40-50. CONCLUSIONS: Compared to the LDE model, the GLDE model provides a better fit to the actual disease incidence data. The RWW appeared to be earlier when estimated with the GLDE model than the LDE model. In addition, the WRW estimated with the GLDE model were more lagged and had a longer warning time.
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Enfermedades Transmisibles , Epidemias , Paperas , Escarlatina , Humanos , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/epidemiología , China/epidemiología , Paperas/epidemiología , Escarlatina/epidemiología , IncidenciaRESUMEN
OBJECTIVE: To investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC). METHODS: A retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications. RESULTS: The study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2). CONCLUSION: CSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.
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Hidrocefalia , Neoplasias Pulmonares , Carcinomatosis Meníngea , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/cirugía , Carcinomatosis Meníngea/complicaciones , Carcinomatosis Meníngea/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Derivación Ventriculoperitoneal/efectos adversosRESUMEN
Yichang is a city in central China in the Hubei Province. This study aimed to estimate the dynamics of the transmissibility of hepatitis C using a mathematical model and predict the transmissibility of hepatitis C in 2030. Data of hepatitis C cases from 13 counties or districts (cities) in Yichang from 2008 to 2016 were collected. A susceptible-infectious-chronic-recovered (SICR) model was developed to fit the data. The transmissibility of hepatitis C at the counties or districts was calculated based on new infections (including infected or chronically infected cases) reported monthly in the city caused by one infectious individual (MNI). The trend of the MNI was fitted and predicted using 11 models, with the coefficient of determination (R2 ) was being used to test the goodness of fit of these models. A total of 3065 cases of hepatitis C were reported in Yichang from 2008 to 2016. The median MNI of Yichang was 0.0768. According to the fitting results and analysis, the trend of transmissibility of hepatitis C in Yichang City conforms with the logarithmic (R2 = 0.918, p < 0.001):MNI = 0.265-0.108 log(t) and exponential (R2 = 0.939, p < 0.001): MNI = 0.344e(-0.278t) models. Hence, the transmission of hepatitis C virus at the county level has a downward trend. In conclusion, the transmissibility of hepatitis C in Yichang has a downward trend. With the current preventive and control measures in place, the spread of hepatitis C can be controlled.
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Hepacivirus , Hepatitis C , China/epidemiología , Ciudades , Hepatitis C/epidemiología , Humanos , Modelos TeóricosRESUMEN
Gibberellins (GAs) modulate diverse developmental processes throughout the plant life cycle. However, the interaction between GAs and the circadian rhythm remains unclear. Here, we report that MUT9p-LIKE KINASE1 (MLK1) and MLK2 mediate the interaction between GAs and the circadian clock to regulate hypocotyl elongation in Arabidopsis thaliana DELLA proteins function as master growth repressors that integrate phytohormone signaling and environmental pathways in plant development. MLK1 and MLK2 interact with the DELLA protein REPRESSOR OF ga1-3 (RGA). Loss of MLK1 and MLK2 function results in plants with short hypocotyls and hyposensitivity to GAs. MLK1/2 and RGA directly interact with CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which targets the promoter of DWARF4 (DWF4) to regulate its roles in cell expansion. MLK1/2 antagonize the ability of RGA to bind CCA1, and these factors coordinately regulate the expression of DWF4 RGA suppressed the ability of CCA1 to activate expression from the DWF4 promoter, but MLK1/2 reversed this suppression. Genetically, MLK1/2 act in the same pathway as RGA and CCA1 in hypocotyl elongation. Together, our results provide insight into the mechanism by which MLK1 and MLK2 antagonize the function of RGA in hypocotyl elongation and suggest that MLK1/2 coordinately mediate the regulation of plant development by GAs and the circadian rhythm in Arabidopsis.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Hipocótilo/crecimiento & desarrollo , Hipocótilo/metabolismo , Giberelinas/metabolismo , Giberelinas/farmacología , Mutación/genética , Regiones Promotoras Genéticas , Unión ProteicaRESUMEN
BACKGROUND: Based on differences in populations and prevention and control measures, the spread of new coronary pneumonia in different countries and regions also differs. This study aimed to calculate the transmissibility of coronavirus disease 2019 (COVID-19), and to evaluate the effectiveness of measures to control the disease in Jilin Province, China. METHODS: The data of reported COVID-19 cases were collected, including imported and local cases from Jilin Province as of March 14, 2019. A Susceptible-Exposed-Infectious-Asymptomatic-Recovered/Removed (SEIAR) model was developed to fit the data, and the effective reproduction number (Reff) was calculated at different stages in the province. Finally, the effectiveness of the measures was assessed. RESULTS: A total of 97 COVID-19 infections were reported in Jilin Province, among which 45 were imported infections (including one asymptomatic infection) and 52 were local infections (including three asymptomatic infections). The model fit the reported data well (R2 = 0.593, P < 0.001). The Reff of COVID-19 before and after February 1, 2020 was 1.64 and 0.05, respectively. Without the intervention taken on February 1, 2020, the predicted cases would have reached a peak of 177,011 on October 22, 2020 (284 days from the first case). The projected number of cases until the end of the outbreak (on October 9, 2021) would have been 17,129,367, with a total attack rate of 63.66%. Based on the comparison between the predicted incidence of the model and the actual incidence, the comprehensive intervention measures implemented in Jilin Province on February 1 reduced the incidence of cases by 99.99%. Therefore, according to the current measures and implementation efforts, Jilin Province can achieve good control of the virus's spread. CONCLUSIONS: COVID-19 has a moderate transmissibility in Jilin Province, China. The interventions implemented in the province had proven effective; increasing social distancing and a rapid response by the prevention and control system will help control the spread of the disease.
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Número Básico de Reproducción , COVID-19 , Control de Enfermedades Transmisibles , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/transmisión , China/epidemiología , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/organización & administración , Control de Enfermedades Transmisibles/normas , Humanos , Incidencia , SARS-CoV-2/aislamiento & purificaciónRESUMEN
BACKGROUND: Post cardiac injury syndrome (PCIS) is induced by myocardial infarction or cardiac surgery, as well as minor insults to the heart such as percutaneous coronary intervention (PCI), or insertion of a pacing lead. PCIS is characterized by pericarditis after injury to the heart. The relatively low incidence makes differential diagnosis of PCIS after PCI or implantation of a pacemaker a challenge. This report describes two typical cases of PCIS. CASE PRESENTATION: The first patient presented with signs of progressive cardiac tamponade that occurred two weeks after implantation of a permanent pacemaker. Echocardiography confirmed the presence of a moderate amount of newly-formed pericardial effusion. The second patient underwent PCI for the right coronary artery. However, despite an uneventful procedure, the patient experienced dyspnea, tightness of chest and cold sweats, and bradycardia two hours after the procedure. Echocardiography findings, which showed a moderate amount of newly-formed pericardial effusion, suggested acute cardiac tamponade, and compromised hemodynamics. Both patients recovered with medication. CONCLUSION: These cases illustrated that PCIS can occur after minor myocardial injury, and that the possibility of PCIS should be considered if there is a history of possible cardiac insult.
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Colchicina/uso terapéutico , Glucocorticoides/uso terapéutico , Lesiones Cardíacas/tratamiento farmacológico , Marcapaso Artificial/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Pericarditis/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Taponamiento Cardíaco/tratamiento farmacológico , Taponamiento Cardíaco/etiología , Quimioterapia Combinada , Lesiones Cardíacas/diagnóstico por imagen , Lesiones Cardíacas/etiología , Humanos , Masculino , Derrame Pericárdico/tratamiento farmacológico , Derrame Pericárdico/etiología , Pericarditis/diagnóstico por imagen , Pericarditis/etiología , Factores de Riesgo , Síndrome , Resultado del TratamientoRESUMEN
The objectives of this study were to evaluate the effects of different salinity levels on tissue histology, blood biochemistry, and genes transcription of the GH/IGF system in juvenile golden trout (Oncorhynchus mykiss). Five experimental salinity levels (0, 8, 16, 24, and 32) were selected to domesticate juvenile O. mykiss for 7 days. Histological characteristics changed with salinity, including higher ionocites area and epithelium thickness in gills, narrow lumen of collecting tubules in kidneys, and high numbers of goblet cells in the intestines. Similarly, increments in slits, degenerate hepatocytes, and individualization of hepatocytes have been shown in fish reared in the 32 salinity group. The lowest triglyceride (TG) and the highest level of total protein (TP) were detected in fish reared at the 32 group. The genes transcription of the GH/IGF system altered in response to the increase of salinity. The present results add to the understanding of the physiological responses of O. mykiss on salinity stress and would be helpful in formulating strategies to optimize the aquaculture of this species in environments with fluctuating patterns of salinity.
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Hormona del Crecimiento/metabolismo , Oncorhynchus mykiss/crecimiento & desarrollo , Salinidad , Somatomedinas/metabolismo , Agua/química , Adaptación Fisiológica/efectos de los fármacos , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Hormona del Crecimiento/genética , Cloruro de Sodio/química , Cloruro de Sodio/farmacología , Somatomedinas/genéticaRESUMEN
BACKGROUND: Overuse of nitrogen fertilizers is often a major practice to ensure sufficient nitrogen demand of high-yielding rice, leading to persistent NH4+ excess in the plant. However, this excessive portion of nitrogen nutrient does not correspond to further increase in grain yields. For finding out the main constraints related to this phenomenon, the performance of NH4+ excess in rice plant needs to be clearly addressed beyond the well-defined root growth adjustment. The present work isolates an acute NH4+ excess condition in rice plant from causing any measurable growth change and analyses the initial performance of such internal NH4+ excess. RESULTS: We demonstrate that the acute internal NH4+ excess in rice plant accompanies readily with a burst of reactive oxygen species (ROS) and initiates the downstream reactions. At the headstream of carbon production, photon caption genes and the activity of primary CO2 fixation enzymes (Rubisco) are evidently suppressed, indicating a reduction in photosynthetic carbon income. Next, the vigorous induction of glutathione transferase (GST) genes and enzyme activities along with the rise of glutathione (GSH) production suggest the activation of GSH cycling for ROS cleavage. Third, as indicated by strong induction of glycolysis / glycogen breakdown related genes in shoots, carbohydrate metabolisms are redirected to enhance the production of energy and carbon skeletons for the cost of ROS scavenging. As the result of the development of these defensive reactions, a carbon scarcity would accumulatively occur and lead to a growth inhibition. Finally, a sucrose feeding cancels the ROS burst, restores the activity of Rubisco and alleviates the demand for the activation of GSH cycling. CONCLUSION: Our results demonstrate that acute NH4+ excess accompanies with a spontaneous ROS burst and causes carbon scarcity in rice plant. Therefore, under overuse of N fertilizers carbon scarcity is probably a major constraint in rice plant that limits the performance of nitrogen.
Asunto(s)
Compuestos de Amonio/metabolismo , Fertilizantes/efectos adversos , Oryza/metabolismo , Fotosíntesis , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Amonio/efectos adversos , Regulación de la Expresión Génica de las Plantas , Glutatión/metabolismo , Oryza/genéticaRESUMEN
Phosphorylation of histone H3 affects transcription, chromatin condensation, and chromosome segregation. However, the role of phosphorylation of histone H2A remains unclear. Here, we found that Arabidopsis thaliana MUT9P-LIKE-KINASE (MLK4) phosphorylates histone H2A on serine 95, a plant-specific modification in the histone core domain. Mutations in MLK4 caused late flowering under long-day conditions but no notable phenotype under short days. MLK4 interacts with CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which allows MLK4 to bind to the GIGANTEA (GI) promoter. CCA1 interacts with YAF9a, a co-subunit of the Swi2/Snf2-related ATPase (SWR1) and NuA4 complexes, which are responsible for incorporating the histone variant H2A.Z into chromatin and histone H4 acetylase activity, respectively. Importantly, loss of MLK4 function led to delayed flowering by decreasing phosphorylation of H2A serine 95, along with attenuated accumulation of H2A.Z and the acetylation of H4 at GI, thus reducing GI expression. Together, our results provide insight into how phosphorylation of H2A serine 95 promotes flowering time and suggest that phosphorylation of H2A serine 95 modulated by MLK4 is required for the regulation of flowering time and is involved in deposition of the histone variant H2A.Z and H4 acetylation in Arabidopsis.
Asunto(s)
Arabidopsis/metabolismo , Flores/fisiología , Histonas/metabolismo , Fosfoserina/metabolismo , Acetilación , Secuencia de Aminoácidos , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Prueba de Complementación Genética , Histonas/química , Mutación/genética , Fosforilación , Fotoperiodo , Regiones Promotoras Genéticas/genética , Unión Proteica , Subunidades de Proteína/metabolismo , Fracciones Subcelulares/metabolismo , Factores de TiempoRESUMEN
The elongation factor suppressor of Ty 5 homolog (Spt5) is a regulator of transcription and histone methylation. In humans, phosphorylation of SPT5 by P-TEFb, a protein kinase composed of Cyclin-dependent kinase 9 (CDK9) and cyclin T, interacts with the RNA polymerase II-associated factor1 (PAF1) complex. However, the mechanism of SPT5 phosphorylation is not well understood in plants. Here, we examine the function of SPT5 in Arabidopsis thaliana and find that spt5 mutant flowers early under long-day and short-day conditions. SPT5 interacts with the CDK-activating kinase 4 (CAK4; CDKD;2) and is specifically phosphorylated by CDKD;2 at threonines. The phosphorylated SPT5 binds VERNALIZATION INDEPENDENCE5 (VIP5), a subunit of the PAF1 complex. Genetic analysis showed that VIP5 acts downstream of SPT5 and CDKD;2 Loss of SPT5 or CDKD;2 function results in early flowering because of decreased amounts of FLOWERING LOCUS C (FLC) transcript. Importantly, CDKD;2 and SPT5 are required for the deposition of VIP5 and the enhancement of trimethylation of histone 3 lysine 4 in the chromatin of the FLC locus. Together, our results provide insight into the mechanism by which the Arabidopsis elongation factor SPT5 recruits the PAF1 complex via the posttranslational modification of proteins and suggest that the phosphorylation of SPT5 by CDKD;2 enables it to recruit VIP5 to regulate chromatin and transcription in Arabidopsis.