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During the Neoproterozoic and Paleoproterozoic eras, geological evidence points to several "Snowball Earth" episodes when most of Earth's surface was covered in ice. These global-scale glaciations represent the most marked climate changes in Earth's history. We show that the impact winter following an asteroid impact comparable in size to the Chicxulub impact could have led to a runaway ice-albedo feedback and global glaciation. Using a state-of-the-art atmosphere-ocean climate model, we simulate the climate response following an impact for preindustrial, Last Glacial Maximum (LGM), Cretaceous-like, and Neoproterozoic climates. While warm ocean temperatures in the preindustrial and Cretaceous-like climates prevent Snowball initiation, the colder oceans of the LGM and cold Neoproterozoic climate scenarios rapidly form sea ice and demonstrate high sensitivity to the initial condition of the ocean. Given suggestions of a cold pre-Snowball climate, we argue the initiation of Snowball Earth by a large impact is a robust possible mechanism, as previously suggested by others, and conclude by discussing geologic tests.
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BACKGROUND: Systemic Inflammatory Response Index (SIRI), a composite inflammatory marker encompassing neutrophils, monocytes, and lymphocytes, has been recognized as a reliable marker of systemic inflammation. This article undertakes an analysis of clinical data from ST-segment Elevation Myocardial Infarction (STEMI) patients, aiming to comprehensively assess the relationship between SIRI, STEMI, and the degree of coronary stenosis. METHODS: The study involved 1809 patients diagnosed with STEMI between the years 2020 and 2023. Univariate and multivariate logistic regression analyses were conducted to evaluate the risk factors for STEMI. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of SIRI and neutrophil-to-lymphocyte ratio (NLR). Spearman correlation analysis was performed to assess the correlation between SIRI, NLR, and the Gensini score (GS). RESULTS: Multivariate logistic regression analysis showed that the SIRI was the independent risk factor for STEMI (adjusted odds ratio (OR) in the highest quartile = 24.96, 95% confidence interval (CI) = 15.32-40.66, P < 0.001). In addition, there is a high correlation between SIRI and GS (ß:28.54, 95% CI: 24.63-32.46, P < 0.001). The ROC curve analysis was performed to evaluate the predictive ability of SIRI and NLR for STEMI patients. The area under the curve (AUC) for SIRI was 0.789. The AUC for NLR was 0.754. Regarding the prediction of STEMI in different gender groups, the AUC for SIRI in the male group was 0.771. The AUC for SIRI in the female group was 0.807. Spearman correlation analysis showed that SIRI exhibited a stronger correlation with GS, while NLR was lower (SIRI: r = 0.350, P < 0.001) (NLR: r = 0.313, P < 0.001). CONCLUSION: The study reveals a strong correlation between the SIRI and STEMI as well as the degree of coronary artery stenosis. In comparison to NLR, SIRI shows potential in predicting acute myocardial infarction and the severity of coronary artery stenosis. Additionally, SIRI exhibits a stronger predictive capability for female STEMI patients compared to males.
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Estenose Coronária , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Estudos Transversais , Contagem de Linfócitos , Linfócitos , Neutrófilos , Estenose Coronária/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica , Estudos RetrospectivosRESUMO
Background: Neutrophil to high-density lipoprotein cholesterol ratio (NHR) has demonstrated predictive value for coronary artery disease (CAD). However, few research has been conducted on the predictive capacity of NHR for Major Adverse Cardiovascular Events (MACE) following Percutaneous Coronary Intervention (PCI) or the degree of coronary artery stenosis in hospitalized ST-segment elevation myocardial infarction (STEMI) patients. Methods: The study involved 486 patients diagnosed with STEMI between the years 2020 and 2023. Univariate and multivariate logistic regression analyses were conducted to evaluate the risk factors for MACE after PCI and severe coronary artery stenosis during hospitalization. Receiver operating characteristic (ROC) curves were generated to determine predictive power of NHR and MHR. Spearman correlation analysis was performed to assess the correlation between NHR, MHR and the Gensini score (GS). Results: Multivariate logistic regression analysis showed that the NHR and MHR were the independent risk factor for MACE during hospitalization in STEMI patients (MHR: the odds ratio (OR)=2.347, 95% confidence interval (CI)=1.082-5.089, P=0.031) (NHR: OR=1.092, 95% CI=1.025-1.165, P=0.004). In addition, NHR was also an independent risk factor for high GS (NHR: OR=1.103, 95% CI=1.047-1.162, P<0.001), and the MHR was not an independent risk factor. The ROC curve analysis was performed to evaluate the predictive ability of NHR and MHR for in-hospital MACE in STEMI patients after primary PCI. The area under the curve (AUC) for NHR was 0.681. The AUC for MHR was 0.672. Regarding the prediction of high GS, the AUC for NHR was 0.649. The AUC for MHR was 0.587. Spearman correlation analysis showed that NHR exhibited stronger correlation with GS, while MHR was lower (NHR: r=0.291, P<0.001) (MHR: r=0.156, P<0.001). Conclusion: These findings highlight the potential clinical utility of NHR as a predictive indicator in STEMI patients after PCI during hospitalization, both for MACE events and the degree of coronary artery stenosis.
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Background: The level of HbA1c can reflect the average level of blood glucose over 3 months, which is the gold standard indicator for monitoring blood glucose. The relationship between the level of HbA1c and the extent of coronary atherosclerosis lesions or the prognosis in diabetes with acute coronary syndrome (ACS) remains poorly understood. Aims: To explore whether the level of HbA1c can evaluate the extent of coronary atherosclerosis lesions or the prognosis in diabetes with acute coronary syndrome (ACS) using the SYNTAX score, the Global Registry of Acute Coronary Events (GRACE) score, left ventricular function (LVEF), left ventricular end-diastolic volume (LVEDV), and major adverse cardiac events (MACEs) in the hospital and 12 months after discharge. Methods: This study was a prospective, randomized, open-label, and parallel group study. Patients with diabetes with ACS were recruited into this study indiscriminately, and all the participants were divided into two groups according to the level of HbA1c: HbA1c level ≤ 7%group and HbA1c level > 7%group. The followings were used as the evaluation indicators: SYNTAX score, GRACE score, LVEF, LVEDV, and MACEs in hospital and 12 months after discharge. Results: A total of 233 patients with diabetes and ACS were enrolled and assigned to two groups according to their level of HbA1c: the HbA1c ≤ 7%group (n = 92) and the HbA1c > 7%group (n = 141). The results showed that the proportion of STEMI was higher in the HbA1c ≤7% group (p < 0.05), while the proportion of NSTEMI has not significantly higher in the HbA1c >7% group (p > 0.05). Regression analysis indicated that HbA1c level was significantly positively correlated with GRACE score (r = 0.156, F = 5.784, p = 0.017, n = 233) and SYNTAX score (r = 0.237, F = 13.788, p < 0.001, n = 233), and there were no statistically significant differences in LVEDV and LVEF between the two groups (p > 0.05). The total MACEs rate showed no significant difference between the two groups during hospitalization (p > 0.05) but showed significant differences at 12 months after discharge (p < 0.05). Conclusions: This study shows that HbA1c level was positively correlated with the extent of coronary atherosclerosis lesions and the prognosis in diabetes with ACS. The higher the HbA1c level is, the more severe the coronary atherosclerotic lesion and the worse the prognosis in diabetes with ACS are.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Diabetes Mellitus , Síndrome Coronariana Aguda/diagnóstico por imagem , Glicemia , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus/epidemiologia , Hemoglobinas Glicadas/análise , Humanos , Prognóstico , Estudos Prospectivos , Medição de RiscoRESUMO
Eukaryotic cells repress global translation and selectively upregulate stress response proteins by altering multiple steps in gene expression. In this study, genome-wide transcriptome analysis of cellular adaptation to thermal stress was performed on the plant pathogenic fungus Fusarium graminearum. The results revealed that profound alterations in gene expression were required for heat shock responses in F. graminearum. Among these proteins, heat shock protein 90 (FgHsp90) was revealed to play a central role in heat shock stress responses in this fungus. FgHsp90 was highly expressed and exclusively localised to nuclei in response to heat stress. Moreover, our comprehensive functional characterisation of FgHsp90 provides clear genetic evidence supporting its crucial roles in the vegetative growth, reproduction, and virulence of F. graminearum. In particular, FgHsp90 performs multiple functions as a transcriptional regulator of conidiation. Our findings provide new insight into the mechanisms underlying adaptation to heat shock and the roles of Hsp90 in fungal development.
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Fusarium/crescimento & desenvolvimento , Fusarium/patogenicidade , Regulação Fúngica da Expressão Gênica/genética , Proteínas de Choque Térmico HSP90/genética , Resposta ao Choque Térmico/genética , Esporos Fúngicos/crescimento & desenvolvimento , Fusarium/genética , Expressão Gênica , Perfilação da Expressão Gênica , Genes Fúngicos/genética , Proteínas de Choque Térmico HSP90/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional/genéticaRESUMO
Zearalenone (ZEA) is an estrogenic mycotoxin that is produced by several Fusarium species, including Fusarium graminearum. One of the ZEA biosynthetic genes, ZEB2, encodes two isoforms of Zeb2 by alternative transcription, forming an activator (Zeb2L-Zeb2L homooligomer) and an inhibitor (Zeb2L-Zeb2S heterodimer) that directly regulate the ZEA biosynthetic genes in F. graminearum. Cyclic AMP-dependent protein kinase A (PKA) signaling regulates secondary metabolic processes in several filamentous fungi. In this study, we investigated the effects of the PKA signaling pathway on ZEA biosynthesis. Through functional analyses of PKA catalytic and regulatory subunits (CPKs and PKR), we found that the PKA pathway negatively regulates ZEA production. Genetic and biochemical evidence further demonstrated that the PKA pathway specifically represses ZEB2L transcription and also takes part in posttranscriptional regulation of ZEB2L during ZEA production. Our findings reveal the intriguing mechanism that the PKA pathway regulates secondary metabolite production by reprograming alternative transcription.
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Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fusarium/genética , Fusarium/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zearalenona/biossíntese , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fusarium/efeitos dos fármacos , Genes Fúngicos , Micotoxinas/análise , Isoformas de Proteínas , Deleção de Sequência , Transdução de Sinais , Transcrição Gênica , Zearalenona/genéticaRESUMO
Cell cycle regulation and the maintenance of genome integrity are crucial for the development and virulence of the pathogenic plant fungus Fusarium graminearum. To identify transcription factors (TFs) related to these processes, four DNA-damaging agents were applied to screen a F. graminearum TF mutant library. Sixteen TFs were identified to be likely involved in DNA damage responses. Fhs1 is a fungal specific Zn(II)2Cys6 TF that localises exclusively to nuclei. fhs1 deletion mutants were hypersensitive to hydroxyurea and defective in mitotic cell division. Moreover, deletion of FHS1 resulted in defects in perithecia production and virulence and led to the accumulation of DNA damage. Our genetic evidence demonstrated that the FHS1-associated signalling pathway for DNA damage response is independent of the ATM or ATR pathways. This study identified sixteen genes involved in the DNA damage response and is the first to characterise the novel transcription factor gene FHS1, which is involved in the DNA damage response. The results provide new insights into mechanisms underlying DNA damage responses in fungi, including F. graminearum.