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Studies have shown that some inflammatory markers can predict the risk of cardiovascular disease (CVD) and affect the structure and function of the heart. However, a causal relationship between inflammatory markers and the cardiac structure and function has not yet been established. Thus, we conducted a 2-sample Mendelian randomization (MR) study to explore the potential causal relationship between inflammatory markers and prognostically-related left ventricular (LV) parameters. Instrumental variables (IVs) for C-reactive protein (CRP), interleukin-6 (IL-6), and myeloperoxidase (MPO) levels were selected from the databases of large genome-wide association studies (GWAS). Summary statistics for LV parameters, including LV mass, ejection fraction, end-diastolic and systolic volumes, and the ratio of LV mass to end-diastolic volume, were obtained from cardiovascular magnetic resonance studies of the UK Biobank (nâ =â 16923). The inverse-variance weighted (IVW) method was the primary analytical method used, and was complemented with the MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Sensitivity analysis was performed to evaluate the robustness of the results. CRP was significantly associated with the LV mass in the IVW method (ßâ =â -0.13 g [95% confidence interval [CI], 0.78 g-1.00 g], Pâ =â .046). A higher standard deviation of genetically-predicted CRP levels was associated with a 0.13â ±â 0.06 g lower LV mass. No causal relationships of IL-6 and MPO with LV parameters were found. No evidence of heterogeneity and pleiotropy was detected. Sensitivity analyses confirmed the robustness of the results. Two-sample MR analysis revealed a causal association between increased CRP level and decreased LV mass, whereas IL-6 and MPO levels did not influence the LV parameters. However, further research is required to validate our findings.
Assuntos
Biomarcadores , Proteína C-Reativa , Estudo de Associação Genômica Ampla , Interleucina-6 , Análise da Randomização Mendeliana , Peroxidase , Humanos , Proteína C-Reativa/análise , Peroxidase/sangue , Peroxidase/genética , Interleucina-6/sangue , Interleucina-6/genética , Biomarcadores/sangue , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Inflamação , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Cyp19a1a is a key enzyme in the pathway that converts androgens into estrogen and is regulated by TGF-ß signaling. Smad4 and FoxH1 are downstream effectors of TGF-ß signaling and may play important roles in ovarian development in M. albus. METHODS: We investigated the expression pattern of the Smad4 and FoxH1 using qRTâPCR and immunofluorescence, then tested the changes of smad4 and foxh1 by qRTâPCR after ovary incubation with FSH in vitro, and analysed the regulation of cyp19a1a transcription by Smad4 and FoxH1 by dual-luciferase reporter assays. RESULTS: We found that Smad4 encoded a putative protein of 449 amino acids and harbored the three conserved domains typical of this protein family. Smad4 and foxh1 exhibited similar expression patterns during ovarian development and after FSH incubation, with Pearson's coefficients of 0.873 and 0.63-0.81, respectively. Furthermore, Smad4, FoxH1 and Cyp19a1a colocalized in the granulosa cells and theca cells of ovaries during the mid-to-late vitellogenic stage. Smad4 repressed cyp19a1a activity via SBE1 (- 1372/-1364) and SBE2 (- 415/-407) in the cyp19a1a promoter, whereas mutating SBE1 or SBE2 restored cyp19a1a promoter activity. Co-overexpression of Smad4 and FoxH1 significantly reduced cyp19a1a promoter activity. CONCLUSIONS: This study provides new insights into the potential functions of transcription factors Smad4 and FoxH1 in ovarian development and the transcriptional regulation mechanism of cyp19a1a in M. albus, which will reveal Smad4/FoxH1-mediated TGF-ß signaling in reproduction and the regulation of the cyp19a1a. Aromatase, encoded by cyp19a1a, is involved in ovarian development and plays an important role in the quality of eggs, as well the sex ratio, of the teleost fish, M. albus. The research on the transcriptional regulation of cyp19a1a has contributed to the understanding of its role in ovarian development. In previous study, it was shown that FoxH1 inhibits cyp19a1a transcription. In the present study, Smad4 was confirmed as a cyp19a1a transcriptional repressor and Smad4 may also coordinate with FoxH1 to repress cyp19a1a transcription. At present, we provide a new perspective for the transcriptional regulation of cyp19a1a by transcription factors Smad4 and FoxH1 in teleost fish ovary. In the future, the regulatory networks of Smad4 and FoxH1 will be further studied and the gene editing technology will be applied to screen specific regulatory factors of cyp191a1a gene, so as to alter the female cycle and modulate the sex ratio of the eggs production.
Assuntos
Aromatase , Enguias , Fatores de Transcrição Forkhead , Ovário , Regiões Promotoras Genéticas , Proteína Smad4 , Animais , Feminino , Ovário/metabolismo , Aromatase/metabolismo , Aromatase/genética , Proteína Smad4/metabolismo , Proteína Smad4/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Enguias/metabolismo , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Hormônio Foliculoestimulante/metabolismoRESUMO
Predicting human's gaze from egocentric videos serves as a critical role for human intention understanding in daily activities. In this paper, we present the first transformer-based model to address the challenging problem of egocentric gaze estimation. We observe that the connection between the global scene context and local visual information is vital for localizing the gaze fixation from egocentric video frames. To this end, we design the transformer encoder to embed the global context as one additional visual token and further propose a novel global-local correlation module to explicitly model the correlation of the global token and each local token. We validate our model on two egocentric video datasets - EGTEA Gaze + and Ego4D. Our detailed ablation studies demonstrate the benefits of our method. In addition, our approach exceeds the previous state-of-the-art model by a large margin. We also apply our model to a novel gaze saccade/fixation prediction task and the traditional action recognition problem. The consistent gains suggest the strong generalization capability of our model. We also provide additional visualizations to support our claim that global-local correlation serves a key representation for predicting gaze fixation from egocentric videos. More details can be found in our website (https://bolinlai.github.io/GLC-EgoGazeEst).
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BACKGROUND: Schizothorax o'connori is an endemic fish distributed in the upper and lower reaches of the Yarlung Zangbo River in China. It has experienced a fourth round of whole gene replication events and is a good model for exploring the genetic differentiation and environmental adaptability of fish in the Qinghai-Tibet Plateau. The uplift of the Qinghai-Tibet Plateau has led to changes in the river system, thereby affecting gene exchange and population differentiation between fish populations. With the release of fish whole genome data, whole genome resequencing has been widely used in genetic evolutionary analysis and screening of selected genes in fish, which can better elucidate the genetic basis and molecular environmental adaptation mechanisms of fish. Therefore, our purpose of this study was to understand the population structure and adaptive characteristics of S. o'connori using the whole-genome resequencing method. RESULTS: The results showed that 23,602,746 SNPs were identified from seven populations, mostly distributed on chromosomes 2 and 23. There was no significant genetic differentiation between the populations, and the genetic diversity was relatively low. However, the Zangga population could be separated from the Bomi, Linzhi, and Milin populations in the cluster analysis. Based on historical dynamics analysis of the population, the size of the ancestral population of S. o'connori was affected by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Glacial Age. The selected sites were mostly enriched in pathways related to DNA repair and energy metabolism. CONCLUSION: Overall, the whole-genome resequencing analysis provides valuable insights into the population structure and adaptive characteristics of S. o'connori. There was no obvious genetic differentiation at the genome level between the S. o'connori populations upstream and downstream of the Yarlung Zangbo River. The current distribution pattern and genetic diversity are influenced by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Ice Age. The selected sites of S. o'connori are enriched in the energy metabolism and DNA repair pathways to adapt to the low temperature and strong ultraviolet radiation environment at high altitude.
Assuntos
Cyprinidae , Raios Ultravioleta , Animais , Tibet , China , Cyprinidae/genética , Análise de Sequência de DNARESUMO
Forkhead box H1 (FoxH1) is a sexually dimorphic gene in Oreochromis niloticus, Oplegnathus fasciatus, and Acanthopagrus latus, indicating that it is essential for gonadal development. In the present study, the molecular characteristics and potential function of FoxH1 and the activation of the cyp19a1a promoter in vitro were evaluated in Monopterus albus. The levels of foxh1 in the ovaries were three times higher than those in the testes and were regulated by gonadotropins (Follicle-Stimulating Hormone and Human Chorionic Gonadotropin). FoxH1 colocalized with Cyp19a1a in the oocytes and granulosa cells of middle and late vitellogenic follicles. In addition, three FoxH1 binding sites were identified in the proximal promoter of cyp19a1a, namely, FH1 (-871/-860), FH2 (-535/-524), and FH3 (-218/-207). FoxH1 overexpression significantly attenuated the activity of the cyp19a1a promoter in CHO cells, and FH1/2 mutation increased promoter activity. Taken together, these results suggest that FoxH1 may act as an important regulator in the ovarian development of M. albus by repressing cyp19a1a promoter activity, which provides a foundation for the study of FoxH1 function in bony fish reproductive processes.
Assuntos
Aromatase , Fatores de Transcrição Forkhead , Smegmamorpha , Animais , Cricetinae , Feminino , Sítios de Ligação , Cricetulus , Enguias/genética , Ovário , Smegmamorpha/genética , Fatores de Transcrição Forkhead/genética , Aromatase/genética , Regiões Promotoras GenéticasRESUMO
To explore the differences in the growth characteristics and population dynamics of Schizothorax wangchiachii populations in the Jinsha River (JSR) and the Yalong River (YLR), samples were collected in the upper reaches of the JSR (n = 230) from 2019 to 2020 and the middle reaches of the YLR (n = 187) from 2017 to 2018. In the JSR and YLR populations, the age range was 11 and 12 years old, respectively, and the best growth equation was the Von Bertalanffy equation. The comparative analysis of the two populations showed that the growth coefficient, initial sexual maturity age and age at first capture of the YLR population were greater than those of the JSR population. Comparing the mortality rates of the two groups, we found that the YLR population had the higher female mortality rate (0.658 years-1) and the lower male mortality rate (0.453 years-1). Our assessment of the three natural mortality rates showed that the Fcur of both male and female populations was greater than F25%, indicating that both populations were in an overexploited state. Therefore, we suggest considering the two groups as separate protection units and implementing management measures such as ecological regulation, restoration of tributary habitat and strengthening of fishing ban monitoring to protect their resources.
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Bmpr2 plays a central role in the regulation of reproductive development in mammals, but its role during ovarian development in fish is still unclear. To ascertain the function of bmpr2 in ovarian development in the ricefield eel, we isolated and characterized the bmpr2 cDNA sequence; the localization of Bmpr2 protein was determined by immunohistochemical staining; and the expression patterns of bmpr2 in ovarian tissue incubated with FSH and hCG in vitro were analyzed. The full-length bmpr2 cDNA was 3311 bp, with 1061 amino acids encoded. Compared to other tissues, bmpr2 was abundantly expressed in the ovary and highly expressed in the early yolk accumulation (EV) stages of the ovary. In addition, a positive signal for Bmpr2 was detected in the cytoplasm of oocytes in primary growth (PG) and EV stages. In vitro, the expression level of gdf9, the ligand of bmpr2, in the 10 ng/mL FSH treatment group was significantly higher after incubation for 4 h than after incubation for different durations. However, bmpr2 expression in the 10 ng/mL FSH treatment group at 2 h, 4 h and 10 h was significantly lower. Importantly, the expression level of bmpr2 and gdf9 in the 100 IU/mL hCG group had similar changes that were significantly decreased at 4 h and 10 h. In summary, Bmpr2 might play a pivotal role in ovarian growth in the ricefield eel, and these results provide a better understanding of the function of bmpr2 in ovarian development and the basic data for further exploration of the regulatory mechanism of gdf9 in oocyte development.
Assuntos
Enguias , Gonadotropinas , Animais , Feminino , Enguias/genética , Enguias/metabolismo , Gonadotropinas/metabolismo , Ovário/metabolismo , Oócitos , Fator de Crescimento Transformador beta/metabolismo , MamíferosRESUMO
Apoptosis plays a key role in the effective removal of excessive and defective germ cells, which is essential for sequential hermaphroditism and sex change in vertebrates. The ricefield eel, Monopterus albus is a protogynous hermaphroditic fish that undergoes a sequential sex change from female to male. Previous studies have demonstrated that apoptosis is involved in sex change in M. albus. However, the apoptotic signaling pathway is unclear. In the current study, we explored the underlying mechanism of apoptosis during gonadal development and focused on the role of the mitochondrial apoptosis signaling pathway in sex change in M. albus. Flow cytometry was performed to detect apoptosis in gonads at five sexual stages and ovary tissues exposed to hydrogen peroxide (H2O2) in vitro. Then the expression patterns of key genes and proteins in the mitochondrial pathway, death receptor pathway and endoplasmic reticulum (ER) pathway were examined. The results showed that the apoptosis rate was significantly increased in the early intersexual stage and then decreased with the natural sex change from female to male. Quantitative real-time PCR revealed that bax, tnfr1, and calpain were mainly expressed in the five stages. ELISA demonstrated that the relative content of cytochrome-c (cyt-c) in the mitochondrial pathway was significantly higher than that of caspase8 and caspase12, with a peak in the early intersexual stage, while the levels of caspase8 and caspase12 peaked in the late intersexual stage. Interestingly, the Pearson's coefficient between cyt-c and the apoptosis rate was 0.705, which suggests that these factors are closely related during the gonadal development of M. albus. Furthermore, the cyt-c signal was found to be increased in the intersexual stage by immunohistochemistry. After incubation with H2O2, the mRNA expression of mitochondrial pathway molecules such as bax, apaf-1, and caspase3 increased in ovary tissues. In conclusion, the present results suggest that the mitochondrial apoptotic pathway may play a more important role than the other apoptotic pathways in sex change in M. albus.
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Transtornos do Desenvolvimento Sexual , Enguias , Animais , Apoptose , Calpaína/metabolismo , Citocromos c/metabolismo , Transtornos do Desenvolvimento Sexual/metabolismo , Enguias/genética , Enguias/metabolismo , Feminino , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Masculino , Oócitos/metabolismo , Ovário/metabolismo , RNA Mensageiro/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: An increasing number of long noncoding RNAs (lncRNAs) have been found to play important roles in sex differentiation and gonad development by regulating gene expression at the epigenetic, transcriptional and posttranscriptional levels. The ricefield eel, Monopterus albus, is a protogynous hermaphroditic fish that undergoes a sequential sex change from female to male. However, the roles of lncRNA in the sex change is unclear. RESULTS: Herein, we performed RNA sequencing to analyse lncRNA expression patterns in five different stages of M. albus development to investigate the roles of lncRNAs in the sex change process. A total of 12,746 lncRNAs (1503 known lncRNAs and 11,243 new lncRNAs) and 2901 differentially expressed lncRNAs (DE-lncRNAs) were identified in the gonads. The target genes of the DE-lncRNAs included foxo1, foxm1, smad3, foxr1, camk4, ar and tgfb3, which were mainly enriched in signalling pathways related to gonadal development, such as the insulin signalling pathway, MAPK signalling pathway, and calcium signalling pathway. We selected 5 highly expressed DE-lncRNAs (LOC109952131, LOC109953466, LOC109954337, LOC109954360 and LOC109958454) for full length amplification and expression pattern verification. They were all expressed at higher levels in ovaries and intersex gonads than in testes, and exhibited specific time-dependent expression in ovarian tissue incubated with follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). The results of quantitative real-time PCR (qRT-PCR) analysis and a dual-luciferase assay showed that znf207, as the gene targeted by LOC109958454, was expressed in multiple tissues and gonadal developmental stages of M. albus, and its expression was also inhibited by the hormones FSH and hCG. CONCLUSIONS: These results provide new insights into the role of lncRNAs in gonad development, especially regarding natural sex changes in fish, which will be useful for enhancing our understanding of sequential hermaphroditism and sex changes in the ricefield eel (M. albus) and other teleosts.
Assuntos
Transtornos do Desenvolvimento Sexual , RNA Longo não Codificante , Smegmamorpha , Animais , Enguias/genética , Feminino , Hormônio Foliculoestimulante/metabolismo , Gônadas , Masculino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Smegmamorpha/genéticaRESUMO
Purpose: Computed tomography (CT) characteristics associated with critical outcomes of patients with coronavirus disease 2019 (COVID-19) have been reported. However, CT risk factors for mortality have not been directly reported. We aim to determine the CT-based quantitative predictors for COVID-19 mortality. Methods: In this retrospective study, laboratory-confirmed COVID-19 patients at Wuhan Central Hospital between December 9, 2019, and March 19, 2020, were included. A novel prognostic biomarker, V-HU score, depicting the volume (V) of total pneumonia infection and the average Hounsfield unit (HU) of consolidation areas was automatically quantified from CT by an artificial intelligence (AI) system. Cox proportional hazards models were used to investigate risk factors for mortality. Results: The study included 238 patients (women 136/238, 57%; median age, 65 years, IQR 51-74 years), 126 of whom were survivors. The V-HU score was an independent predictor (hazard ratio [HR] 2.78, 95% confidence interval [CI] 1.50-5.17; p = 0.001) after adjusting for several COVID-19 prognostic indicators significant in univariable analysis. The prognostic performance of the model containing clinical and outpatient laboratory factors was improved by integrating the V-HU score (c-index: 0.695 vs. 0.728; p < 0.001). Older patients (age ≥ 65 years; HR 3.56, 95% CI 1.64-7.71; p < 0.001) and younger patients (age < 65 years; HR 4.60, 95% CI 1.92-10.99; p < 0.001) could be further risk-stratified by the V-HU score. Conclusions: A combination of an increased volume of total pneumonia infection and high HU value of consolidation areas showed a strong correlation to COVID-19 mortality, as determined by AI quantified CT.
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We have studied the Co2FeAl thin films with different thicknesses epitaxially grown on GaAs (001) by molecular beam epitaxy. The magnetic properties and spin polarization of the films were investigated by in-situ magneto-optic Kerr effect (MOKE) measurement and spin-resolved angle-resolved photoemission spectroscopy (spin-ARPES) at 300 K, respectively. High spin polarization of 58% (±7%) was observed for the film with thickness of 21 unit cells (uc), for the first time. However, when the thickness decreases to 2.5 uc, the spin polarization falls to 29% (±2%) only. This change is also accompanied by a magnetic transition at 4 uc characterized by the MOKE intensity. Above it, the film's magnetization reaches the bulk value of 1000 emu/cm3. Our findings set a lower limit on the thickness of Co2FeAl films, which possesses both high spin polarization and large magnetization.