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KEY MESSAGE: Three major QTLs qA01, qB04.1 and qB05 for VLCFA content and their corresponding allele-specific markers will benefit peanut low VLCFA breeding, and a candidate gene Arahy.IF1JV3 was predicted. Peanut is a globally significant oilseed crop worldwide, and contains a high content (20%) of saturated fatty acid (SFA) in its seeds. As high level SFA intake in human dietary may increase the cardiovascular disease risk, reducing the SFA content in peanut is crucial for improving its nutritional quality. Half of the SFAs in peanut are very long-chain fatty acids (VLCFA), so reducing the VLCFA content is a feasible strategy to decrease the total SFA content. Luoaowan with extremely low VLCFA (4.80%) was crossed with Jihua16 (8.00%) to construct an F2:4 population. Three major QTLs including qA01, qB04.1 and qB05 for VLCFA content were detected with 4.43 ~ 14.32% phenotypic variation explained through linkage mapping. Meanwhile, three genomic regions on chromosomes B03, B04 and B05 were identified via BSA-seq approach. Two co-localized intervals on chromosomes B04 (100.10 ~ 103.97 Mb) and B05 (6.39 ~ 10.90 Mb) were identified. With markers developed based on SNP/InDel variations in qA01 between the two parents, the remaining interval was refined to 103.58 ~ 111.14 Mb. A candidate gene Arahy.IF1JV3 encoding a ß-ketoacyl-CoA synthase was found in qA01, and its expression level in Luoaowan was significantly lower than that in Jihua16. Allele-specific markers targeting qA01, qB04.1 and qB05 were developed and validated in F4 population, and an elite line with high oleic, low VLCFA (5.05%) and low SFA (11.48%) contents was selected. This study initially revealed the genetic mechanism of VLCFA content, built a marker-assisted selection system for low VLCFA breeding, and provided an effective method to decrease the SFA content in peanut.
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Arachis , Melhoramento Vegetal , Humanos , Arachis/genética , Mapeamento Cromossômico , Locos de Características Quantitativas , Ácidos GraxosRESUMO
BACKGROUND: The protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate the macrophage-mediated pro-inflammatory response after MI and its potential mechanism are worth further exploration. METHODS: To determine the baseline plasma levels of CoQ10 by LC-MS/MS, healthy controls and MI patients (n = 11 each) with age- and gender-matched were randomly enrolled. Additional MI patients were consecutively enrolled and randomized into the blank control (n = 59) or CoQ10 group (n = 61). Follow-ups were performed at 1- and 3-month to assess cardiac function after percutaneous coronary intervention (PCI). In the animal study, mice were orally administered CoQ10/vehicle daily and were subjected to left anterior descending coronary artery (LAD) ligation or sham operation. Echocardiography and serum BNP measured by ELISA were analyzed to evaluate cardiac function. Masson staining and WGA staining were performed to analyze the myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Immunofluorescence staining was performed to assess the infiltration of IL1ß/ROS-positive macrophages into the ischemic myocardium. Flow cytometry was employed to analyze the recruitment of myeloid immune cells to the ischemic myocardium post-MI. The expression of inflammatory indicators was assessed through RNA-seq, qPCR, and western blotting (WB). RESULTS: Compared to controls, MI patients showed a plasma deficiency of CoQ10 (0.76 ± 0.31 vs. 0.46 ± 0.10 µg/ml). CoQ10 supplementation significantly promoted the recovery of cardiac function in MI patients at 1 and 3 months after PCI. In mice study, compared to vehicle-treated MI mice, CoQ10-treated MI mice showed a favorable trend in survival rate (42.85% vs. 61.90%), as well as significantly alleviated cardiac dysfunction, myocardial fibrosis, and cardiac hypertrophy. Notably, CoQ10 administration significantly suppressed the recruitment of pro-inflammatory CCR2+ macrophages into infarct myocardium and their mediated inflammatory response, partially by attenuating the activation of the NLR family pyrin domain containing 3 (NLRP3)/Interleukin-1 beta (IL1ß) signaling pathway. CONCLUSIONS: These findings suggest that CoQ10 can significantly promote early recovery of cardiac function after MI. CoQ10 may function by inhibiting the recruitment of CCR2+ macrophages and suppressing the activation of the NLRP3/IL1ß pathway in macrophages. TRIAL REGISTRATION: Date of registration 09/04/2021 (number: ChiCTR2100045256).
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Infarto do Miocárdio , Intervenção Coronária Percutânea , Ubiquinona , Animais , Humanos , Camundongos , Cromatografia Líquida , Modelos Animais de Doenças , Fibrose , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espectrometria de Massas em Tandem , Ubiquinona/análogos & derivados , Ubiquinona/sangue , Remodelação VentricularRESUMO
Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.
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Vascular endothelial growth factor receptor 2 (VEGFR2)/KDR plays a critical role in tumor growth, diffusion, and invasion. The amino acid sequence homology of KDR between mouse and human in the VEGF ligand-binding domain was low, thus the WT mice could not be used to evaluate Abs against human KDR, and the lack of a suitable mouse model hindered both basic research and drug developments. Using the CRISPR/Cas9 technique, we successfully inserted different fragments of the human KDR coding sequence into the chromosomal mouse Kdr exon 4 locus to obtain an hKDR humanized mouse that can be used to evaluate the marketed Ab ramucirumab. In addition, the humanized mAb VEGFR-HK19 was developed, and a series of comparative assays with ramucirumab as the benchmark revealed that VEGFR-HK19 has higher affinity and superior antiproliferation activity. Moreover, VEGFR-HK19 selectively inhibited tumor growth in the hKDR mouse model but not in WT mice. The most important binding epitopes of VEGFR2-HK19 are D257, L313, and T315, located in the VEGF binding region. Therefore, the VEGFR2-HK19 Ab inhibits tumor growth by blocking VEGF-induced angiogenesis, inflammation, and promoting apoptosis. To our best knowledge, this novel humanized KDR mouse fills the gaps both in an animal model and the suitable in vivo evaluation method for developing antiangiogenesis therapies in the future, and the newly established humanized Ab is expected to be a drug candidate possibly benefitting tumor patients.
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Anticorpos Neutralizantes , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Camundongos , Animais , Anticorpos Neutralizantes/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fosforilação , Ligação Proteica , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptores de Fatores de Crescimento do Endotélio VascularRESUMO
BACKGROUND: There is insufficient evidence of associations between incident dyslipidemia with PM1 (submicronic particulate matter) and PM1-2.5 (intermodal particulate matter) in the middle-aged and elderly. We aimed to determine the long-term effects of PM1 and PM1-2.5 on incident dyslipidemia respectively. METHODS: We studied 6976 individuals aged ≥45 from the China Health and Retirement Longitudinal Study from 2013 to 2018. The concentrations of particular matter (PM) for every individual's address were evaluated using a satellite-based spatiotemporal model. Dyslipidemia was evaluated by self-reported. The generalized linear mixed model was applied to quantify the correlations between PM and incident dyslipidemia. RESULTS: After a 5-year follow-up, 333 (4.77%) participants developed dyslipidemia. Per 10 µg/m³ uptick in four-year average concentrations of PMs (PM1 and PM1-2.5) corresponded to 1.11 [95% confidence interval (CI): 1.01-1.23)] and 1.23 (95% CI: 1.06-1.43) fold risks of incident dyslipidemia. Nonlinear exposure-response curves were observed between PM and incident dyslipidemia. The effect size of PM1 on incident dyslipidemia was slightly higher in males [1.14 (95% CI: 0.98-1.32) vs. 1.04 (95% CI: 0.89-1.21)], the elderly [1.23 (95% CI: 1.04-1.45) vs. 1.03 (95% CI: 0.91-1.17)], people with less than primary school education [1.12 (95% CI: 0.94-1.33) vs. 1.08 (95% CI: 0.94-1.23)], and solid cooking fuel users [1.17 (95% CI: 1.00-1.36) vs. 1.06 (95% CI: 0.93-1.21)], however, the difference was not statistically significant (Z = -0.82, P = 0.413; Z = -1.66, P = 0.097; Z = 0.32, P = 0.752; Z = -0.89, P = 0.372). CONCLUSIONS: Long-term exposure to PM1 and PM1-2.5 were linked with an increased morbidity of dyslipidemia in the middle-aged and elderly population. Males, the elderly, and solid cooking fuel users had higher risk. Further studies would be warranted to establish an accurate reference value of PM to mitigate growing dyslipidemia.
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Poluentes Atmosféricos , Poluição do Ar , Dislipidemias , Masculino , Pessoa de Meia-Idade , Humanos , Idoso , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/análise , Estudos de Coortes , Estudos Longitudinais , China/epidemiologia , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Exposição Ambiental/análise , Poluição do Ar/análiseRESUMO
BACKGROUND: Although there is evidence of long-term effects of particulate matter (PM) on cardiovascular diseases (CVD), researches about long-term effects of PM1 on CVD are limited. We aimed to examine the long-term effects and magnitude of PM, especially PM1, on incident CVD in China. METHODS: We included 6016 participants aged ≥ 45 years without CVD at baseline in 2011 from the China Health and Retirement Longitudinal Study. Personal PM (PM1, PM2.5, and PM10) concentrations were estimated using geocoded residential address. Generalized linear mixed models and SHapley Additive exPlanation were utilized to calculate the impacts and contributions of PM on CVD. Sensitivity analyses were used to check the robustness. RESULTS: After a follow up of 4-year, 481 (7.99 %) participants developed CVD. Per 10 µg/m3 uptick in 1-year average concentrations of PM1, PM2.5 and PM10 was associated with a 1.20 [95 % confidence interval (CI): 1.05-1.37], 1.13 (95 % CI: 1.11-1.15), and 1.10 (95 % CI: 1.06-1.13) fold risk of incident CVD, respectively. The 2-year average concentrations of PM1, PM2.5 and PM10 were associated with incident CVD, corresponding to a 1.03 (95 % CI: 0.96-1.10), 1.11 (95 % CI: 1.02-1.21), and 1.09 (95 % CI: 1.03-1.15) fold risk, respectively. The SHapley Additive exPlanation values of PM1, PM2.5, and PM10 were 0.170, 0.153, and 0.053, respectively, corresponding to the first, second, and fifth among all air pollutants. Effects of PM1, PM2.5 and PM10 on CVD remained statistically significant in two-pollutant models. The elderly, males, smokers and alcohol drinkers tended to have slightly higher effects, while the differences were not statistically significant (all P-values > 0.05) between subgroups. CONCLUSION: Long-term exposure to PM1, PM2.5, and PM10 was associated with an increased incidence of CVD. The smaller the particle size, the more important it was for incident CVD indicating that emphasis should be placed on small size of PM.
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As environmental changes are inevitable, online algorithms that can track the variation of acoustic transfer functions are preferred in sound zone control (SZC) systems. In this paper, it is found that for the time domain SZC, the nonuniqueness problem caused by the coupling in multichannel transfer function modeling can be solved with time-varying control filters. To keep a stable acoustic contrast (AC) performance irrespective of environmental changes and also avoid the extreme distortion introduced by maximizing the AC in the time domain, the objective of maintaining a desired level of AC is used and an adaptive control algorithm is developed. The simulations validate that the proposed method tracks the environmental changes and adapts the control filters to give a stable AC performance.
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Disruption of the dynamic equilibrium of microtubules can induce cell cycle arrest in G2/M phase and apoptosis. Hence, discovery of novel tubulin polymerization inhibitors is very necessary and an important task in drug research and development for treatment of various tumors. In this investigation, 50 compounds were screened as microtubule stabilizers targeting the taxane site by combination of molecular docking methods. Among these hits, hits 19 and 38 with novel scaffolds exhibited the highest anti-proliferative activity with IC50 ranging from 9.50 to 13.81 µM in four cancer cell lines. The molecular dynamics simulations confirmed that tubulin and two hits could form stable systems. Meanwhile, the mechanism of the interactions between tubulin and two hits at simulated physiological conditions were probed. The in vitro tubulin polymerization assay revealed hits 19 and 38 were able to promote tubulin polymerization in a dose-dependent manner. Further, the immunofluorescence assay suggested that hits 19 and 38 could accelerate microtubule assembly in A549 and HeLa cells. Finally, studies on antitumor activity indicated that hits 19 and 38 induced G2/M phase cell cycle arrest and apoptosis, and inhibited cancer cell motility and migration in A549 and HeLa cells. Importantly, hit38 exhibited better anti-tubulin and anti-cancer activity than hit19 in A549 and HeLa cells. Therefore, these results suggest that hit38 represents a promising microtubule stabilizer for treating cancer and deserves further investigation.
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Antineoplásicos , Simulação de Dinâmica Molecular , Antineoplásicos/química , Sítios de Ligação , Hidrocarbonetos Aromáticos com Pontes , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Microtúbulos/metabolismo , Simulação de Acoplamento Molecular , Taxoides , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/químicaRESUMO
In sound zone control, the pressure matching (PM) algorithm is generally considered to achieve relatively low acoustic contrast (AC) regardless of the desired sound field. In this paper, we propose a generalized PM framework to generate a desired sound field with variable AC. The framework indicates that the choice of the desired sound field solely determines the AC performance of PM when the physical setting and acoustic environment remain unchanged. In the extreme, PM obtains the same AC as the acoustic contrast control method, which is widely accepted as the algorithm leading to the maximum AC. Based on the proposed framework, we design a variant coordinate descent algorithm to adjust the desired sound field by maximizing the AC under the constraint of the reconstruction error. Simulation results validate the efficacy and flexibility of the proposed framework in constrained sound zone control.
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Serum and glucocorticoid-regulated kinase 1 (SGK1), as a serine threonine protein kinase of the AGC family, regulates different enzymes, transcription factors, ion channels, transporters, and cell proliferation and apoptosis. Inhibition of SGK1 is considered as a valuable approach for the treatment of various metabolic diseases. In this investigation, virtual screening methods, including pharmacophore models, Bayesian classifiers, and molecular docking, were combined to discover novel inhibitors of SGK1 from the database with 29,158 compounds. Then, the screened compounds were subjected to ADME/T, PAINS and drug-likeness analysis. Finally, 28 compounds with potential inhibition activity against SGK1 were selected for biological evaluation. The kinase inhibition activity test revealed that among these 28 hits, hit15 exhibited the highest inhibition activity against SGK1, which gave 44.79% inhibition rate at the concentration of 10 µM. In order to further investigate the interaction mechanism of hit15 and SGK1 at simulated physiological conditions, a molecular dynamics simulation was performed. The molecular dynamics simulation demonstrated that hit15 could bind to the active site of SGK1 and form stable interactions with key residues, such as Tyr178, ILE179, and VAL112. The binding free energy of the SGK1-hit15 was -48.90 kJ mol-1. Therefore, the identified hit15 with novel scaffold may be a promising lead compound for development of new SGK1 inhibitors for various diseases treatment.
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Simulação de Dinâmica Molecular , Proteínas Serina-Treonina Quinases , Teorema de Bayes , Ligantes , Simulação de Acoplamento MolecularRESUMO
Acoustic contrast control (ACC) is one of the most commonly utilized sound zone control methods, which maximizes the ratio of the average squared sound pressure in two control zones. The time-domain formulation of ACC (TACC) is usually preferred since it can optimize the whole bandwidth in a single step and the resulting control filter is guaranteed to be causal. Many researchers have noted that TACC suffers from uneven frequency response. However, a convincing theoretical explanation of this problem is yet to be investigated. In this letter, an asymptotically equivalent frequency-domain form of TACC is constructed, based on which it can be proven that TACC has the tendency of extracting the specific frequency component with the highest contrast. Simulation results validate the efficacy of this theoretical analysis.
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Immune checkpoint inhibitor (ICI) therapies have shown great promise in cancer treatment. However, the intra-heterogeneity is a major barrier to reasonably classifying the potential benefited patients. Comprehensive heterogeneity analysis is needed to solve these clinical issues. In this study, the samples from pan-cancer and independent breast cancer datasets were divided into four tumor immune microenvironment (TIME) subtypes based on tumor programmed death ligand 1 (PD-L1) expression level and tumor-infiltrating lymphocyte (TIL) state. As the combination of the TIL Z score and PD-L1 expression showed superior prediction of response to ICI in multiple data sets compared to other methods, we used the TIL Z score and PD-L1 to classify samples. Therefore, samples were divided by combined TIL Z score and PD-L1 to identify four TIME subtypes, including type I (3.24%), type II (43.24%), type III (6.76%), and type IV (46.76%). Type I was associated with favorable prognosis with more T and DC cells, while type III had the poorest condition and composed a higher level of activated mast cells. Furthermore, TIME subtypes exhibited a distinct genetic and transcriptional feature: type III was observed to have the highest mutation rate (77.92%), while co-mutations patterns were characteristic in type I, and the PD-L1 positive subgroup showed higher carbohydrates, lipids, and xenobiotics metabolism compared to others. Overall, we developed a robust method to classify TIME and analyze the divergence of prognosis, immune cell composition, genomics, and transcriptomics patterns among TIME subtypes, which potentially provides insight for classification of TIME and a referrable theoretical basis for the screening benefited groups in the ICI immunotherapy.
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Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Feminino , Seguimentos , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico , Taxa de SobrevidaRESUMO
The extracellular matrix (ECM) spatiotemporally controls cell fate; however, dysregulation of ECM remodeling can lead to tumorigenesis and cancer development by providing favorable conditions for tumor cells. Proteoglycans (PGs) and glycosaminoglycans (GAGs) are the major macromolecules composing ECM. They influence both cell behavior and matrix properties through direct and indirect interactions with various cytokines, growth factors, cell surface receptors, adhesion molecules, enzymes, and glycoproteins within the ECM. The classical features of PGs/GAGs play well-known roles in cancer angiogenesis, proliferation, invasion, and metastasis. Several lines of evidence suggest that PGs/GAGs critically affect broader aspects in cancer initiation and the progression process, including regulation of cell metabolism, serving as a sensor of ECM's mechanical properties, affecting immune supervision, and participating in therapeutic resistance to various forms of treatment. These functions may be implemented through the characteristics of PGs/GAGs as molecular bridges linking ECM and cells in cell-specific and context-specific manners within the tumor microenvironment (TME). In this review, we intend to present a comprehensive illustration of the ways in which PGs/GAGs participate in and regulate several aspects of tumorigenesis; we put forward a perspective regarding their effects as biomarkers or targets for diagnoses and therapeutic interventions.
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Glicosaminoglicanos/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Proteoglicanas/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Proliferação de Células/fisiologia , Resistencia a Medicamentos Antineoplásicos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Glicosaminoglicanos/análise , Humanos , Masculino , Neoplasias/irrigação sanguínea , Neoplasias/terapia , Neovascularização Patológica , Proteoglicanas/análise , Microambiente TumoralRESUMO
Online secondary path modeling is always appealing in active noise control due to the benefit of tracking the variations in the secondary path while exerting noise control simultaneously. However, the auxiliary noise usually utilized in online modeling contributes to the residual noise and deteriorates the noise control performance. This problem is more severe in multi-channel active control systems. Recently, it has been revealed that the secondary path can be identified using the output of the control source directly without injecting any auxiliary noise. In this letter, this strategy is extended to the multi-channel case. The reliability of the secondary path modeling is theoretically proven, and the effectiveness of the proposed multi-channel simultaneous modeling and control system is validated through simulations using measured impulse responses.
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The similarity between the identification of secondary path in feedforward active noise control and the channel identification in stereo echo cancellation is revealed in this paper. Accordingly, the convergence behavior of the ANC system can be analyzed by investigating the joint auto-correlation matrix of the reference and the filtered reference signal. It is proved that the straightforward secondary path modeling can be carried out without the injection of any additive noise as long as the control filter is of a sufficiently long length. Furthermore, by taking advantage of the time-varying characteristic of the control filter, effective modeling of the secondary path can even be achieved without any restriction on the control filter length.
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Owing to the poor prognosis, novel biomarkers for lung adenocarcinoma (LACA) are needed nowadays. The aim of the study was to identify the differential miRNAs expression between lung cancer and normal tissues and evaluate the prognostic values of the miRNAs. Multidimensional data of 528 samples were retrieved from The Cancer Genome Atlas archive. Data analysis was based on a computational approach to detect survival-associated molecular signatures. A total of 191 differentially expressed miRNAs were identified between LACA tissues and normal tissues, including 88 up-regulated and 103 down-regulated miRNAs. The Kaplan-Meier survival method revealed the prognostic function of the three miRNAs (miR-1293, miR-873 and miR-1914). Cox regression analysis showed that the three-miRNA signature was an independent prognostic factor in LACA. The functional enrichment analysis suggested that the target genes of three miRNAs may be involved in various pathways related to the cancer. This study demonstrated that the three-miRNA signature (miR-1293, miR-873 and miR-1914) could be used as a prognostic marker in LACA.
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Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Ontologia Genética , Humanos , Masculino , MicroRNAs/metabolismo , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: Transcription factors operate as important switches of transcription networks, and NAC (NAM, ATAF, and CUC) transcription factors are a plant-specific family involved in multiple biological processes. However, this gene family has not been systematically characterized in cotton. RESULTS: Here we identify a large number of genes with conservative NAC domains in four cotton species, with 147 found in Gossypium arboreum, 149 in G. raimondii, 267 in G. barbadense and 283 in G. hirsutum. Predicted membrane-bound NAC genes were also identified. Phylogenetic analysis showed that cotton NAC proteins clustered into seven subfamilies and homologous protein pairs showed similar characteristics. Evolutionary property analysis revealed that purifying selection of NAC genes occurred between diploid and polyploid cotton species, and variation analysis showed GhNAC genes may have been subjected to selection and domestication. NAC proteins showed extensive transactivation and this was dependent on the C-terminus. Some development and stress related cis-elements were enriched in the promoters of GhNAC genes. Comprehensive expression analysis indicated that 38 GhNAC genes were candidates for involvement in fiber development, and 120 in stress responses. Gene co-expression network analysis revealed relationships between fiber-associated NAC genes and secondary cell wall (SCW) biosynthesis genes. CONCLUSIONS: NAC genes were identified in diploid and tetraploid cotton, revealing new insights into their evolution, variation and homology relationships. Transcriptome analysis and co-expression network indicated roles for GhNAC genes in cotton fiber development and stress response, and NAC genes may prove useful in molecular breeding programmes.
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Fibra de Algodão , Gossypium/metabolismo , Fatores de Transcrição/fisiologia , Sequência Conservada/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Genes de Plantas/fisiologia , Variação Genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Gossypium/genética , Gossypium/crescimento & desenvolvimento , Filogenia , Estresse Fisiológico , Sintenia/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional/genética , Ativação Transcricional/fisiologiaRESUMO
JASMONATE ZIM-domain (JAZ) family proteins are involved in regulating diverse biological processes in plants. However, their functions have not been well characterized in cotton (Gossypium spp.). In the present study, 13, 15, 25 and 30 JAZ genes were identified in Gossypium arboretum, Gossypium raimondii, Gossypium barbadense and Gossypium hirsutum, respectively, based on gene homology. Selection and variation analyses showed that the single nucleotide polymorphism (SNP) density of GhJAZ genes in wild species was much higher than that in domesticated species. Expression pattern analysis showed that all the GhJAZ genes are expressed in at least one tissue and respond to one or more stress factors, as well as being induced by some phytohormones. The co-expression network indicated that GhJAZ genes might mediate multiple stress response pathways. Yeast two-hybrid (Y2H) experiments showed extensive interactions among GhJAZ proteins, including homo- and heteromeric interactions. Overexpressing one member of the JAZ gene family, GhJAZ2 (Gh_D06G0810), significantly enhanced sensitivity to salt stress in transgenic cotton. Transcriptome analysis indicated that GhJAZ2 regulates stress responses possibly by participating in α-linolenic acid metabolism and jasmonate signaling, and is involved in the repression of GhMYC2 regulated by GhJAZ2. Our data provide important clues for further elucidating the functions of JAZ genes in cotton.
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Ciclopentanos/metabolismo , Gossypium/fisiologia , Oxilipinas/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico/fisiologia , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Gossypium/efeitos dos fármacos , Gossypium/genética , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Família Multigênica , Filogenia , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Polimorfismo de Nucleotídeo Único , Domínios Proteicos , Domínios e Motivos de Interação entre Proteínas , Transdução de Sinais , Técnicas do Sistema de Duplo-Híbrido , Ácido alfa-Linolênico/genética , Ácido alfa-Linolênico/metabolismoRESUMO
BACKGROUND: Fine particulate matter (PM2.5) has been implicated in various health concerns. However, a comprehensive understanding of the specific PM2.5 components affecting depression remains limited. METHODS: This study conducted a Cox proportional-hazards model to assess the effect of PM2.5 components on the incidence of depression based on the China Health and Retirement Longitudinal Study (CHARLS). Participants with 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) score of 10 or higher were classified as exhibiting depression. RESULTS: Our findings demonstrated a significant positive correlation between long-term exposure to black carbon (BC), sulfate (SO42-), and organic matter (OM) components of PM2.5 and the prevalence of depression. Per 1 Interquartile Range (IQR) increment in 3-year average concentrations of BC, OM, and SO42- were associated with the hazard ratio (HR) of 1.54 (95 % confidence intervals (CI): 1.44, 1.64), 1.24 (95%CI: 1.16, 1.34) and 1.25 (95%CI: 1.16, 1.35). Notably, females, younger individuals, those with lower educational levels, urban residents, individuals who were single, widowed, or divorced, and those living in multi-story houses exhibited heightened vulnerability to the adverse effects of PM2.5 components on depression. LIMITATIONS: Firstly, pollutant data is confined to subjects' fixed addresses, overlooking travel and international residence history. Secondly, the analysis only incorporates five fine particulate components, leaving room for further investigation into the remaining fine particulate components in future studies. CONCLUSIONS: This study provides robust evidence supporting the detrimental impact of PM2.5 components on depression. The identification of specific vulnerable populations contributes to a deeper understanding of the underlying mechanisms involved in the relationship between PM2.5 components and depression.
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Depressão , Material Particulado , Modelos de Riscos Proporcionais , Humanos , Material Particulado/efeitos adversos , Feminino , China/epidemiologia , Masculino , Pessoa de Meia-Idade , Idoso , Depressão/epidemiologia , Estudos Longitudinais , Exposição Ambiental/efeitos adversos , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Incidência , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Estudos de Coortes , Prevalência , Fuligem/efeitos adversosRESUMO
Continuous electroencephalogram (cEEG) plays a crucial role in monitoring and postoperative evaluation of critical patients with extensive EEG abnormalities. Recently, the temporal variability of dynamic resting-state functional connectivity has emerged as a novel approach to understanding the pathophysiological mechanisms underlying diseases. However, little is known about the underlying temporal variability of functional connections in critical patients admitted to neurology intensive care unit (NICU). Furthermore, considering the emerging field of network physiology that emphasizes the integrated nature of human organisms, we hypothesize that this temporal variability in brain activity may be potentially linked to other physiological functions. Therefore, this study aimed to investigate network variability using fuzzy entropy in 24-hour dynamic resting-state networks of critical patients in NICU, with an emphasis on exploring spatial topology changes over time. Our findings revealed both atypical flexible and robust architectures in critical patients. Specifically, the former exhibited denser functional connectivity across the left frontal and left parietal lobes, while the latter showed predominantly short-range connections within anterior regions. These patterns of network variability deviating from normality may underlie the altered network integrity leading to loss of consciousness and cognitive impairment observed in these patients. Additionally, we explored changes in 24-hour network properties and found simultaneous decreases in brain efficiency, heart rate, and blood pressure between approximately 1 pm and 5 pm. Moreover, we observed a close relationship between temporal variability of resting-state network properties and other physiological indicators including heart rate as well as liver and kidney function. These findings suggest that the application of a temporal variability-based cEEG analysis method offers valuable insights into underlying pathophysiological mechanisms of critical patients in NICU, and may present novel avenues for their condition monitoring, intervention, and treatment.