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This work reports on the emergence of quantum Griffiths singularity (QGS) associated with the magnetic field induced superconductor-metal transition (SMT) in unconventional Nd_{0.8}Sr_{0.2}NiO_{2} infinite layer superconducting thin films. The system manifests isotropic SMT features under both in-plane and perpendicular magnetic fields. Importantly, after scaling analysis of the isothermal magnetoresistance curves, the obtained effective dynamic critical exponents demonstrate divergent behavior when approaching the zero-temperature critical point B_{c}^{*}, identifying the QGS characteristics. Moreover, the quantum fluctuation associated with the QGS can quantitatively explain the upturn of the upper critical field around zero temperature for both the in-plane and perpendicular magnetic fields in the phase boundary of SMT. These properties indicate that the QGS in the Nd_{0.8}Sr_{0.2}NiO_{2} superconducting thin film is isotropic. Moreover, a higher magnetic field gives rise to a metallic state with the resistance-temperature relation R(T) exhibiting lnT dependence among the 2-10 K range and T^{2} dependence of resistance below 1.5 K, which is significant evidence of Kondo scattering. The interplay between isotropic QGS and Kondo scattering in the unconventional Nd_{0.8}Sr_{0.2}NiO_{2} superconductor can illustrate the important role of rare region in QGS and help to uncover the exotic superconductivity mechanism in this system.
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BACKGROUND: This study aimed to explore the associations between brain structures, cognition, and motor control in participants with mild cognitive impairment (MCI), with a focus on dual-task performance. METHODS: Thirty MCI patients and thirty healthy controls were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Structural magnetic resonance imaging data were analyzed using voxel-based morphometry (VBM) to calculate brain parenchyma volume and gray matter volume (GMV). Participants performed single- and dual-task Timed Up and Go (TUG) tests, and the correlations between significant GMV differences and task execution time was analyzed. RESULTS: MCI patients showed significantly lower MoCA scores, particularly in visuospatial/executive, attention, and delayed recall domains (p < 0.05). Dual-task TUG execution time was significantly increased in MCI patients (p < 0.05). The GMV in the right anterior lobe of the cerebellum and both insulae was positively correlated with visuospatial/executive scores (FDR-corrected, p < 0.05). The GMV of the right cerebellar anterior lobe and insula were significantly reduced in MCI patients (p < 0.05). The GMV of the right cerebellar anterior lobe was negatively correlated with dual-task execution time (r = -0.32, p = 0.012). CONCLUSION: Smaller GMV in the right anterior lobe of the cerebellum was associated with impaired dual-task performance, which may provide more evidence for the neural mechanisms of cognitive and motor function impairments in MCI.
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Purpose: To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), and the association of the presence and severity of WMH with OA characteristics. Methods: This cross-sectional study included 44 eyes of 25 patients with WMH and 38 eyes of 19 controls. The Fazekas scale was adopted as criteria for evaluating the severity of white matter hyperintensities. The morphological characteristics of the OA were measured on the basis of three-dimensional reconstruction. The hemodynamic parameters of the OA were calculated using computational fluid dynamics simulations. Results: Compared with the control group, the diameter (16.0±0.27 mm vs. 1.71±0.18 mm, P=0.029), median blood flow velocity (0.12 m/s vs. 0.22 m/s, P<0.001), mass flow ratio (2.16% vs. 3.94%, P=0.012) and wall shear stress (2.65 Pa vs. 9.31 Pa, P<0.001) of the OA in patients with WMH were significantly decreased. After adjusting for confounding factors, the diameter, blood flow velocity, wall shear stress, and mass flow ratio of the OA were significantly associated with the presence of WMH. Male sex and high low-density protein level were associated with moderate-to-severe total WMH, and smoking was associated with the moderate-to-severe periventricular WMH. Conclusions: The diameter, blood flow velocity, mass flow ratio, and wall shear stress of the OA were independently associated with the presence of WMH. Atherosclerosis might be involved in the common mechanism of the occurrence of WMH and the OA changes.
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Hemodinâmica , Artéria Oftálmica , Substância Branca , Humanos , Masculino , Feminino , Artéria Oftálmica/diagnóstico por imagem , Artéria Oftálmica/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Substância Branca/irrigação sanguínea , Substância Branca/patologia , Estudos Transversais , Hemodinâmica/fisiologia , Pessoa de Meia-Idade , Idoso , Velocidade do Fluxo Sanguíneo , Imageamento por Ressonância Magnética , AdultoRESUMO
Introduction: This study investigates the role of hypoxia-related genes in the neuroprotective efficacy of Yang Xue oral liquid (YXKFY) in Alzheimer's disease (AD) and Parkinson's disease (PD). Methods and results: Using differential expression and weighted gene co-expression network analysis (WGCNA), we identified 106 and 9 hypoxia-associated genes in AD and PD, respectively, that are implicated in the transcriptomic and proteomic profiles. An artificial intelligence-driven hypoxia signature (AIDHS), comprising 17 and 3 genes for AD and PD, was developed and validated across nine independent cohorts (n = 1713), integrating 10 machine learning algorithms and 113 algorithmic combinations. Significant associations were observed between AIDHS markers and immune cells in AD and PD, including naive CD4+ T cells, macrophages, and neutrophils. Interactions with miRNAs (hsa-miR-1, hsa-miR-124) and transcription factors (USF1) were also identified. Single-cell RNA sequencing (scRNA-seq) data highlighted distinct expression patterns of AIDHS genes in various cell types, such as high expression of TGM2 in endothelial cells, PDGFRB in endothelial and mesenchymal cells, and SYK in microglia. YXKFY treatment was shown to repair cellular damage and decrease reactive oxygen species (ROS) levels. Notably, genes with previously dysfunctional expression, including FKBPL, TGM2, PPIL1, BLVRB, and PDGFRB, exhibited significant recovery after YXKFY treatment, associated with riboflavin and lysicamine. Conclusion: The above genes are suggested to be central to hypoxia and neuroinflammation responses in AD and PD, and are potential key mediators of YXKFY's neuroprotective action.
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BACKGROUND: This study aims to quantify the impacts of chilling at the grain filling stage on rice yield and grain quality. A factorial experiment with four levels of temperature and duration of chilling treatments at the early and late grain filling stages was conducted in 2017, 2018 and 2019. RESULTS: Per 10 °C·day increase in the accumulated cooling degree day at the early and late grain filling stages, the rice emergence-maturity duration was delayed by 0.8% (0.6%) and rice yield decreased by 2.2% (1.7%). Chilling at the early grain filling stage decreased the rice heading rate, while chilling at the late grain filling stage increased rice amylose but decreased protein content. For chilling treatment at the early grain filling stage, rice yield and grain quality were mainly correlated with seed-setting rate, whereas for chilling treatment at the late grain filling stage the rice yield and grain quality were mainly correlated with 1000-grain weight. CONCLUSION: This study improved the understanding of how chilling at the grain filling stages affects rice phenology, yield and grain quality, providing a theoretical basis for maintaining rice yield while ensuring grain quality. The results could be used to guide the rice-growing community in combating chilling at grain filling stages. © 2024 Society of Chemical Industry.
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Spinal diseases and frozen shoulder are prevalent health problems in Asian populations. Early assessment and treatment are very important to prevent the disease from getting worse and reduce pain. In the field of computer vision, it is a challenging problem to assess the range of motion. In order to realize efficient, real-time and accurate assessment of the range of motion, an assessment system combining MediaPipe and YOLOv5 technologies was proposed in this study. On this basis, Convolutional Block Attention Module (CBAM) is introduced into the YOLOv5 target detection model, which can enhance the extraction of feature information, suppress background interference, and improve the generalization ability of the model. In order to meet the requirements of large-scale computing, a client/server (C/S) framework structure is adopted. The evaluation results can be obtained quickly after the client uploads the image data, providing a convenient and practical solution. In addition, a game of "Picking Bayberries" was developed as an auxiliary treatment method to provide patients with interesting rehabilitation training.
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Bursite , Amplitude de Movimento Articular , Doenças da Coluna Vertebral , Humanos , Bursite/fisiopatologia , Bursite/terapia , Bursite/diagnóstico , Doenças da Coluna Vertebral/diagnóstico , Doenças da Coluna Vertebral/fisiopatologia , Doenças da Coluna Vertebral/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
Background: Liver tumor segmentation based on medical imaging is playing an increasingly important role in liver tumor research and individualized therapeutic decision-making. However, it remains a challenging in terms of the accuracy of automatic segmentation of liver tumors. Therefore, we aimed to develop a novel deep neural network for improving the results from the automatic segmentation of liver tumors. Methods: This paper proposes the attention-guided context asymmetric fusion network (AGCAF-Net), combining attention guidance and fusion context modules on the basis of a residual neural network for the automatic segmentation of liver tumors. According to the attention-guided context block (AGCB), the feature map is first divided into multiple small blocks, the local correlation between features is calculated, and then the global nonlocal fusion module (GNFM) is used to obtain the global information between pixels. Additionally, the context pyramid module (CPM) and asymmetric semantic fusion module (AFM) are used to obtain multiscale features and resolve the feature mismatch during feature fusion, respectively. Finally, we used the liver tumor segmentation benchmark (LiTS) dataset to verify the efficiency of our designed network. Results: Our results showed that AGCAF-Net with AFM and CPM is effective in improving the accuracy of liver tumor segmentation, with the Dice coefficient increasing from 82.5% to 84.1%. The segmentation results of liver tumors by AGCAF-Net were superior to those of several state-of-the-art U-net methods, with a Dice coefficient of 84.1%, a sensitivity of 91.7%, and an average symmetric surface distance of 3.52. Conclusions: AGCAF-Net can obtain better matched and accurate segmentation in liver tumor segmentation, thus effectively improving the accuracy of liver tumor segmentation.
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Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.
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Doenças Cardiovasculares , Pequeno RNA não Traduzido , RNA de Transferência , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Animais , RNA de Transferência/genética , RNA de Transferência/metabolismo , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/uso terapêutico , Pequeno RNA não Traduzido/metabolismoAssuntos
Genótipo , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , China/epidemiologia , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Infecções por Coronavirus/virologia , Infecções por Coronavirus/epidemiologia , Filogenia , Virulência , Doenças Transmissíveis Emergentes/virologia , Doenças Transmissíveis Emergentes/epidemiologia , Genoma ViralRESUMO
BACKGROUND: The aim of the study was to investigate the relationship between sedentary behavior, screen time and MetS among Chinese children and adolescents aged 7-17 years. Data was obtained from the China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017. METHODS: Data on sedentary time, screen time, and MetS indicators were obtained through physical and health questionnaires, anthropometric measurements, and clinical examinations. MetS was defined according to the Cook's criteria. Wilcoxon rank sum test and chi-square test were applied for comparisons of measurement data and counting data, respectively. The relationship between sedentary time, screen time, and MetS and its components was analyzed using a multivariate logistic regression model. RESULTS: The prevalence of MetS among 7-17-year-old students in 2016-2017 was 5.45%. Compared to those with low sedentary behavior, in high sedentary behavior groups, the prevalence of abdominal obesity, high TG, low HDL-C, and MetS was high in boys, and the prevalence of abdominal obesity, high TG, hyperglycemia, and MetS was high in girls. Moreover, for those who reported ≥ 3 h/day of screen time, the prevalence of abdominal obesity, low HDL-C, and MetS was higher in boys, and the prevalence of abdominal obesity and MetS was higher in girls. After adjusting for confounding variables, the risks of abdominal obesity, high TG, low HDL-C, and MetS were higher in high-level sedentary time group, and the risks of abdominal obesity and MetS were 1.15 and 1.14 times higher for those who spent ≥ 3 h/day on screen time, respectively. CONCLUSIONS: This study shows that high levels of sedentary time and screen time were associated with an increased likelihood of MetS among Chinese children and adolescents aged 7-17 years. Reducing sedentary behavior and screen time may contribute to the prevention of metabolic diseases.
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Síndrome Metabólica , Tempo de Tela , Comportamento Sedentário , Humanos , Adolescente , Feminino , Masculino , Síndrome Metabólica/epidemiologia , China/epidemiologia , Criança , Prevalência , Estudos Transversais , Fatores de Risco , População do Leste AsiáticoRESUMO
AIMS: Formylpeptide receptors (FPRs) play a critical role in the regulation of inflammation, an important driver of hypertension-induced end-organ damage. We have previously reported that the biased FPR small-molecule agonist, compound17b (Cmpd17b), is cardioprotective against acute, severe inflammatory insults. Here, we reveal the first compelling evidence of the therapeutic potential of this novel FPR agonist against a longer-term, sustained inflammatory insult, i.e. hypertension-induced end-organ damage. The parallels between the murine and human hypertensive proteome were also investigated. METHODS AND RESULTS: The hypertensive response to angiotensin II (Ang II, 0.7â mg/kg/day, s.c.) was attenuated by Cmpd17b (50â mg/kg/day, i.p.). Impairments in cardiac and vascular function assessed via echocardiography were improved by Cmpd17b in hypertensive mice. This functional improvement was accompanied by reduced cardiac and aortic fibrosis and vascular calcification. Cmpd17b also attenuated Ang II-induced increased cardiac mitochondrial complex 2 respiration. Proteomic profiling of cardiac and aortic tissues and cells, using label-free nano-liquid chromatography with high-sensitivity mass spectrometry, detected and quantified â¼6000 proteins. We report hypertension-impacted protein clusters associated with dysregulation of inflammatory, mitochondrial, and calcium responses, as well as modified networks associated with cardiovascular remodelling, contractility, and structural/cytoskeletal organization. Cmpd17b attenuated hypertension-induced dysregulation of multiple proteins in mice, and of these, â¼110 proteins were identified as similarly dysregulated in humans suffering from adverse aortic remodelling and cardiac hypertrophy. CONCLUSION: We have demonstrated, for the first time, that the FPR agonist Cmpd17b powerfully limits hypertension-induced end-organ damage, consistent with proteome networks, supporting development of pro-resolution FPR-based therapeutics for treatment of systemic hypertension complications.
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BACKGROUND: Early prediction of survival of hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is vital. We aimed to establish a nomogram to predict the survival probability of AECOPD patients. METHODS: Retrospectively collected data of 4601 patients hospitalized for AECOPD. These patients were randomly divided into a training and a validation cohort at a 6:4 ratio. In the training cohort, LASSO-Cox regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of AECOPD patients. A model was established based on 3 variables and visualized by nomogram. The performance of the model was assesed by AUC, C-index, calibration curve, decision curve analysis in both cohorts. RESULTS: Coexisting arrhythmia, invasive mechanical ventilation (IMV) usage and lower serum albumin values were found to be significantly associated with lower survival probability of AECOPD patients, and these 3 predictors were further used to establish a prediction nomogram. The C-indexes of the nomogram were 0.816 in the training cohort and 0.814 in the validation cohort. The AUC in the training cohort was 0.825 for 7-day, 0.807 for 14-day and 0.825 for 21-day survival probability, in the validation cohort this were 0.796 for 7-day, 0.831 for 14-day and 0.841 for 21-day. The calibration of the nomogram showed a good goodness-of-fit and decision curve analysis showed the net clinical benefits achievable at different risk thresholds were excellent. CONCLUSION: We established a nomogram based on 3 variables for predicting the survival probability of AECOPD patients. The nomogram showed good performance and was clinically useful.
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Nomogramas , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Progressão da Doença , Prognóstico , Modelos de Riscos Proporcionais , Mortalidade Hospitalar , Idoso de 80 Anos ou mais , Fatores de RiscoRESUMO
Rice wine, known as yellow wine in China and Japan, possesses considerable nutritional value and holds significant global influence. This study addresses the challenge of preserving rice wine, which is prone to rancidity due to its low alcohol content. Conventional storage techniques employing pottery jars often result in substantial spoilage losses. Through rigorous investigation, this research identifies a polarization phenomenon exhibited by degraded rice wine when subjected to high-frequency microwaves(>60GHz), presenting a pioneering method for detecting spoilage, even within sealed containers. Employing a multi-channel microwave radar apparatus, the study delves into the susceptibility of rice wine to electromagnetic waves across various frequencies, uncovering pronounced polarization traits in deteriorated samples within the E-band microwave spectrum. Furthermore, lab-controlled simulations elucidate a direct correlation between physicochemical alterations and high-frequency Radar Cross Section (RCS) signals during the wine's deterioration process. A novel six-membered Hydrated Cluster hypothesis is proposed, offering insights into the molecular mechanisms underlying this phenomenon. Additionally, dielectric property assessments conducted using vector network analyzers (VNA) reveal noteworthy enhancements in the dielectric constant of deteriorated rice wine, particularly within the high-frequency domain, thereby augmenting detectability. These findings carry implications for refining rice wine preservation techniques and contribute to the advancement of non-destructive testing technologies, enabling the detection of rice wine deterioration or indications thereof, even within sealed vessels.
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Oryza , Vinho , Vinho/análise , Oryza/química , Micro-Ondas , Japão , Fenômenos Eletromagnéticos , ChinaRESUMO
RATIONALE AND OBJECTIVES: This study aims to assess whether a radiomics-based nomogram correlates with a higher risk of future cerebro-cardiovascular events in patients with asymptomatic carotid plaques. Additionally, it investigates the nomogram's contribution to the revised Framingham Stroke Risk Profile (rFSRP) for predicting cerebro-cardiovascular risk. MATERIALS AND METHODS: Predictive models aimed at identifying an increased risk of future cerebro-cardiovascular events were developed and internally validated at one center, then externally validated at two other centers. Survival curves, constructed using the Kaplan-Meier method, were compared through the log-rank test. RESULTS: This study included a total of 2009 patients (3946 images). The final nomogram was generated using multivariate Cox regression variables, including dyslipidemia, lumen diameter, plaque echogenicity, and ultrasonography (US)-based radiomics risk. The Harrell's concordance index (C-index) for predicting events-free survival (EFS) was 0.708 in the training cohort, 0.574 in the external validation cohort 1, 0.632 in the internal validation cohort, and 0.639 in the external validation cohort 2. The final nomogram showed a significant increase in C-index compared to the clinical, conventional US, and US-based radiomics models (all P < 0.05). Furthermore, the final nomogram-assisted method significantly improved the sensitivity and accuracy of radiologists' visual qualitative score of plaque (both P < 0.001). Among 1058 patients with corresponding 1588 plaque US images classified as low-risk by the rFSRP, 75 (7.1%) patients with corresponding 93 (5.9%) carotid plaque images were appropriately reclassified to the high-risk category by the final nomogram. CONCLUSION: The radiomics-based nomogram demonstrated accurate prediction of cerebro-cardiovascular events in patients with asymptomatic carotid plaques. It also improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque and enhanced the risk stratification ability of rFSRP. SUMMARY: The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques. KEY RESULTS: The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques. The radiomics-based nomogram improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque. The radiomics-based nomogram improved the discrimination of high-risk populations from low-risk populations in asymptomatic patients with carotid atherosclerotic plaques and the risk stratification capability of the rFSRP.
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Spurs, which mainly appear in roosters, are protrusions near the tarsometatarsus on both sides of the calves of chickens, and are connected to the tarsometatarsus by a bony core. As a male-biased morphological characteristic, the diameter and length of spurs vary significantly between different individuals, mainly related to genetics and age. As a specific behavior of hens, egg-laying also varies greatly between individuals in terms of traits such as age at first egg (AFE), egg weight (EW), and so on. At present, there are few studies on chicken spurs. In this study, we investigated the inheritance pattern of the spur trait in roosters with different phenotypes and the correlations between spur length, body weight at 18 weeks of age (BW18), shank length at 18 weeks of age (SL18), and the egg-laying trait in hens (both hens and roosters were from the same population and were grouped according to their family). These traits related to egg production included AFE, body weight at first egg (BWA), and first egg weight (FEW). We estimated genetic parameters based on pedigree and phenotype data, and used variance analysis to calculate broad-sense heritability for correcting the parameter estimation results. The results showed that the heritability of male left and right spurs ranged from 0.6 to 0.7. There were significant positive correlations between left and right spur length, BW18, SL18, and BWA, as well as between left and right spur length and AFE. We selected 35 males with the longest spurs and 35 males with the shortest spurs in the population, and pooled them into two sets to obtain the pooled genome sequencing data. After genome-wide association and genome divergency analysis by FST, allele frequency differences (AFDs), and XPEHH methods, we identified 7 overlapping genes (CENPE, FAT1, FAM149A, MANBA, NFKB1, SORBS2, UBE2D3) and 14 peak genes (SAMD12, TSPAN5, ENSGALG00000050071, ENSGALG00000053133, ENSGALG00000050348, CNTN5, TRPC6, ENSGALG00000047655,TMSB4X, LIX1, CKB, NEBL, PRTFDC1, MLLT10) related to left and right spur length through genome-wide selection signature analysis and a genome-wide association approach. Our results identified candidate genes associated with chicken spurs, which helps to understand the genetic mechanism of this trait and carry out subsequent research around it.
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BACKGROUNDS: A growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs. OBJECTIVES: This study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs. METHODS: Genetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets. RESULTS: There was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10- 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10- 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10- 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10- 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042). CONCLUSIONS: Our study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA.
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Doenças Autoimunes , Hipolipemiantes , Análise da Randomização Mendeliana , Humanos , Doenças Autoimunes/genética , Doenças Autoimunes/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Polimorfismo de Nucleotídeo Único , Lipídeos/sangue , Mapas de Interação de Proteínas/genética , Hidroximetilglutaril-CoA Redutases/genéticaRESUMO
We described a copper(I)-catalyzed atom economic and selective hydroamination-cyclization of alkynyl-tethered quinazolinones to prepare a variety of indole-fused pyrazino[1,2-a]quinazolinones in good to excellent yields ranging from 39 %-99 % under mild reaction conditions. Control experiments revealed that coordination-directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination-cyclization of alkynes at the N1-atom instead of N3-atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole-fused pyrazino[1,2-a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions.
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MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression. Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses, miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus, therapeutic strategies, and challenges.
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Artrite Reumatoide , Lúpus Eritematoso Sistêmico , MicroRNAs , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , AnimaisRESUMO
Poria cocos (Schw.) Wolf (PCW) are the dried sclerotia of Poaceae fungus Poria cocos that contain many biological activity ingredients such as polysaccharides and triterpenoids. The carbohydrates from Poria cocos have been proven to possess anti-inflammatory and antioxidant effects. This study aimed to investigate the impact and mechanism of Poria cocos oligosaccharides (PCO) protecting mice against acute lung injury (ALI). We examined the histopathological analysis of lung injury, inflammatory, and edema levels to evaluate the benefits of PCO during ALI. As a result, PCO improved the lipopolysaccharide (LPS) induced lung injury and decreased the inflammatory cytokines of lung tissue. Simultaneously, PCO alleviated lung edema by regulating the expression of aquaporin5 (AQP5) and epithelial Na+ channel protein (ENaC-α). Additionally, untargeted metabolomics was performed on the plasma of ALI mice via HUPLC-Triple-TOF/MS. The results indicated that linoleic acid, linolenic acid, arachidonic acid, carnosine, glutamic acid, and 1-methylhistamine were the biomarkers in ALI mice. Besides, metabolic pathway analysis suggested PCO affected the histidine and fatty acid metabolism, which were closely associated with inflammation and oxidative reaction of the host. Consequently, the effects of PCO inhibiting inflammation and edema might relate to the reducing pro-inflammatory mediators and the reverse of abnormal metabolic pathways.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Metabolômica , Oligossacarídeos , Wolfiporia , Animais , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Camundongos , Metabolômica/métodos , Lipopolissacarídeos/toxicidade , Oligossacarídeos/farmacologia , Masculino , Wolfiporia/química , Anti-Inflamatórios/farmacologia , Biomarcadores/sangue , Modelos Animais de Doenças , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Antioxidantes/farmacologiaRESUMO
The bird beak is mainly functioned as feeding and attacking, and its shape has extremely important significance for survival and reproduction. In chickens, since beak shape could lead to some disadvantages including pecking and waste of feed, it is important to understand the inheritance of chicken beak shape. In the present study, we firstly established 4 indicators to describe the chicken beak shapes, including upper beak length (UL), lower beak length (LL), distance between upper and lower beak tips (DB) and upper beak curvature (BC). And then, we measured the 4 beak shape indicators as well as some production traits including body weight (BW), shank length (SL), egg weight (EW), eggshell strength (ES) of a layer breed, Rhode Island Red (RIR), in order to estimate genetic parameters of chicken beak shape. The heritabilities of UL and LL were 0.41 and 0.37, and the heritabilities of DB and BC were 0.22 and 0.21, indicating that beak shape was a highly or mediumly heritable. There were significant positive genetic and phenotypic correlations among UL, LL, and DB. And UL was positively correlated with body weight (BW18) and shank length (SL18) at 18 weeks of age in genetics, and DB was positively correlated with BC in terms of genetics and phenotype. We also found that layers of chicken cages played a role on beak shape, which could be attributed to the difference of lightness in different cage layers. By a genome-wide association study (GWAS) for the chicken UL, we identified 9 significant candidate genes associated with UL in RIR. For the variants with low minor allele frequencies (MAF <0.01) and outside of high linkage disequilibrium (LD) regions, we also conducted rare variant association studies (RVA) and GWAS to find the association between genotype and phenotype. We also analyzed transcriptomic data from multiple tissues of chicken embryos and revealed that all of the 9 genes were highly expressed in beak of chicken embryos, indicating their potential function for beak development. Our results provided the genetic foundation of chicken beak shape, which could help chicken breeding on beak related traits.