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As a representative of the fourth-generation light sources, the High Energy Photon Source (HEPS) in Beijing, China, utilizes a multi-bend achromat lattice to obtain an approximately 100 times emittance reduction compared with third-generation light sources. New technologies bring new challenges to operate the storage ring. In order to meet the beam commissioning requirements of HEPS, a new framework for the development of high-level applications (HLAs) has been created. The key part of the new framework is a dual-layer physical module to facilitate the seamless fusion of physical simulation models with the real machine, allowing for fast switching between different simulation models to accommodate the various simulation scenarios. As a framework designed for development of physical applications, all variables are based on physical quantities. This allows physicists to analytically assess measurement parameters and optimize machine parameters in a more intuitive manner. To enhance both extensibility and adaptability, a modular design strategy is utilized, partitioning the entire framework into discrete modules in alignment with the requirements of HLA development. This strategy not only facilitates the independent development of each module but also minimizes inter-module coupling, thereby simplifying the maintenance and expansion of the entire framework. To simplify the development complexity, the design of the new framework is implemented using Python and is called Python-based Accelerator Physics Application Set (Pyapas). Taking advantage of Python's flexibility and robust library support, we are able to develop and iterate quickly, while also allowing for seamless integration with other scientific computing applications. HLAs for both the HEPS linac and booster have been successfully developed. During the beam commissioning process at the linac, Pyapas's ease of use and reliability have significantly reduced the time required for the beam commissioning operators. As a development framework for HLA designed for the new-generation light sources, Pyapas has the versatility to be employed with HEPS, as well as with other comparable light sources, due to its adaptability.
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INTRODUCTION: Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint inflammation and bone damage, that not only restricts patient activity but also tends to be accompanied by a series of complications, seriously affecting patient prognosis. Peroxisome proliferator-activated receptor gamma (PPARG), a receptor that controls cellular metabolism, regulates the function of immune cells and stromal cells. Previous studies have shown that PPARG is closely related to the regulation of inflammation. However, the role of PPARG in regulating the pathological processes of RA is poorly understood. MATERIALS AND METHODS: PPARG expression was examined in the synovial tissues and peripheral blood mononuclear cells (PBMCs) from RA patients and the paw of collagen-induced arthritis (CIA) model rats. Molecular biology experiments were designed to examine the effect of PPARG and cannabidiol (CBD) on RAW264.7 cells and CIA rats. RESULTS: The results reveal that PPARG accelerates reactive oxygen species (ROS) clearance by promoting autophagy, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation. Notably, CBD may be a promising candidate for understanding the mechanism by which PPARG regulates autophagy-mediated inflammation. CONCLUSIONS: Taken together, these findings indicate that PPARG may have a role for distinguishing between RA patients and healthy control, and for distinguishing RA activity; moreover, PPARG could be a novel pharmacological target for alleviating RA through the mediation of autophagy. CBD can act as a PPARG agonist that alleviates the inflammatory progression of RA.
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Artrite Experimental , Artrite Reumatoide , Autofagia , Inflamação , PPAR gama , Espécies Reativas de Oxigênio , Animais , Feminino , Humanos , Masculino , Camundongos , Ratos , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Artrite Reumatoide/imunologia , Autofagia/efeitos dos fármacos , Canabidiol/farmacologia , Modelos Animais de Doenças , Inflamassomos/metabolismo , Inflamação/metabolismo , Inflamação/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PPAR gama/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.
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N6-methyladenosine (m6A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m6A writers, erasers, and readers, m6A modulation is involved in myriad physiological and pathological processes. Extensive studies have demonstrated m6A modulation in diverse tumours, with effects on tumorigenesis, metastasis, and resistance. Recent evidence has revealed an emerging role of m6A modulation in tumour immunoregulation, and divergent m6A methylation patterns have been revealed in the tumour microenvironment. To depict the regulatory role of m6A methylation in the tumour immune microenvironment (TIME) and its effect on immune evasion, this review focuses on the TIME, which is characterized by hypoxia, metabolic reprogramming, acidity, and immunosuppression, and outlines the m6A-regulated TIME and immune evasion under divergent stimuli. Furthermore, m6A modulation patterns in anti-tumour immune cells are summarized.
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Evasão da Resposta Imune , Microambiente Tumoral , Humanos , Metilação , Adenosina , CarcinogêneseRESUMO
BACKGROUND: To investigate the difference between the predicted preoperative corneal ablation depth and the measured ablation depth for femtosecond laser in situ keratomileusis (FS-LASIK) in patients with different degrees of myopia, and to analyze the source of the difference. METHODS: A total of 55 patients (109 eyes) were included in this study. Multiple logistics regression was applied to analyze the sources affecting postoperative refractive outcomes. The difference between the preoperative predicted corneal ablation depth and the 1-day postoperative ablation depth in patients with different degrees of myopia was explored using linear regression. Corneal biomechanical parameters influencing error in ablation depth calculation were examined using multiple linear regression. RESULTS: One hundred and nine eyes were divided into low to moderate myopia (55 eyes, myopia of 6 D or less), high myopia (45 eyes, myopia ranging from 6 D to a maximum of 9 D), and very high myopia group (9 eyes, myopia greater than 9 D) based on preoperative refractive error (spherical equivalent). Postoperative visual outcomes were comparable among the three groups of patients, with no significant difference in uncorrected visual acuity (UCVA). We did find notable disparities in spherical equivalent (SE) and central corneal thickness (CCT) in patients with different degrees of myopia at 1 day postoperatively (all p < 0.001). Logistic regression analysis showed that error in ablation depth calculation was an independent risk factor for refractive outcomes one day after surgery (OR = 1.689, 95% CI: 1.366 - 2.089). There was a substantial discrepancy in error in ablation depth calculation at 1 day postoperatively between the three groups. The measured ablation depth of the laser platform was lower than the predicted ablation depth in the low to moderate myopia and very high myopia groups, but the opposite was true in the high myopia group. Pre-operative SE (p < 0.001) and corneal front minimum radius of curvature (Front Rmin) (p = 0.007) obviously influenced the error in ablation depth calculation. CONCLUSIONS: Error in ablation depth calculation values vary significantly between patients with different degrees of myopia and correlate highly with preoperative SE and Front Rmin. At the same time, the available evidence suggests that error in ablation depth calculation is an influential factor in postoperative refractive status, so it is imperative to control error in ablation depth calculation.
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Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Humanos , Estudos Prospectivos , Lasers de Excimer/uso terapêutico , Córnea/cirurgia , Refração Ocular , Miopia/cirurgiaRESUMO
Periodontitis is a chronic inflammatory disease that starts with pathogenic bacteria and is mediated by a combination of multiple factors. Psychosomatic factors are considered to be one of the most critical risk factors for periodontal disease. Psychological stress may threaten periodontal immune homeostasis in multiple ways by affecting the hypothalamic-pituitary-adrenal cortex system, the locus ceruleus-sympathetic-adrenal medulla system, and the peptidergic nervous system. In this review, we outline the complex role of psychological stress in promoting the development of periodontal disease, focusing on the effects of stress on flora metabolism, tissue inflammation, and alveolar bone homeostasis. At the same time, we broadly and deeply summarize the potential mechanisms of psychological stress-induced periodontal disease, emphasize the importance of neuroimmune modulation for periodontal health, and expect to provide a new perspective for periodontal science based on psychoneuroimmunology.
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Doenças Periodontais , Periodontite , Humanos , Estresse Psicológico/metabolismo , Bactérias , Fatores de RiscoRESUMO
The electron beam generated in laser plasma accelerators (LPAs) has two main initial weaknesses - a large beam divergence (up to a few milliradians) and a few percent level energy spread. They reduce the beam brightness and worsen the coherence of the LPA-based light source. To achieve fully coherent radiation, several methods have been proposed for generating strong microbunching on LPA beams. In these methods, a seed laser is used to induce an angular modulation into the electron beam, and the angular modulation is converted into a strong density modulation through a beamline with nonzero longitudinal position and transverse angle coupling. In this paper, an alternative method to generate microbunching into the LPA beam by using a seed laser that induces an energy modulation and transverse-longitudinal coupling beamlines that convert the energy modulation into strong density modulation is proposed. Compared with the angular modulation methods, the proposed method can use more than one order of magnitude lower seed laser power to achieve similar radiation performance. Simulations show that with the proposed method a coherent pulse of a few microjoules pulse energy and femtosecond duration can be generated with a typical LPA beam.
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X-ray free-electron lasers (XFELs) open a new era of X-ray based research by generating extremely intense X-ray flashes. To further improve the spectrum brightness, a self-seeding FEL scheme has been developed and demonstrated experimentally. As the next step, new-generation FELs with high repetition rates are being designed, built and commissioned around the world. A high repetition rate would significantly speed up the scientific research; however, alongside this improvement comes new challenges surrounding thermal management of the self-seeding monochromator. In this paper, a new configuration for self-seeding FELs is proposed, operated under a high repetition rate which can strongly suppress the thermal effects on the monochromator and provides a narrow-bandwidth FEL pulse. Three-dimension time-dependent simulations have been performed to demonstrate this idea. With this proposed configuration, high-repetition-rate XFEL facilities are able to generate narrow-bandwidth X-ray pulses without obvious thermal concern on the monochromators.
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Coherence time is one of the fundamental characteristics of light sources. Methods based on autocorrelation have been widely applied from optical domain to soft X-rays to characterize the radiation coherence time. However, for the hard X-ray regime, due to the lack of proper mirrors, it is extremely difficult to implement such autocorrelation scheme. In this paper, a novel approach for characterizing the coherence time of a hard X-ray free-electron laser (FEL) is proposed and validated numerically. A phase shifter is adopted to control the correlation between X-ray and microbunched electrons. The coherence time of the FEL pulse can be extracted from the cross-correlation. Semi-analytical analysis and three-dimensional time-dependent numerical simulations are presented to elaborate the details. A coherence time of 218.2 attoseconds for 6.92 keV X-ray FEL pulses is obtained in our simulation based on the configuration of Linac Coherent Light Source. This approach provides critical temporal coherence diagnostics for X-ray FELs, and is decoupled from machine parameters, applicable for any photon energy, radiation brightness, repetition rate and FEL pulse duration.
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Methyl chloride (CH3Cl) and methyl bromide (CH3Br) are the predominant carriers of natural chlorine and bromine from the troposphere to the stratosphere, which can catalyze the destruction of stratospheric ozone. Here, penguin colony soils (PCS) and the adjacent tundra soils (i.e., penguin-lacking colony soils, PLS), seal colony soils (SCS), tundra marsh soils (TMS), and normal upland tundra soils (UTS) in coastal Antarctica were collected and incubated for the first time to confirm that these soils were CH3Cl and CH3Br sources or sinks. Overall, tundra soil acted as a net sink for CH3Cl and CH3Br with potential flux ranges from -18.1 to -2.8 pmol g-1 d-1 and -1.32 to -0.24 pmol g-1 d-1, respectively. The deposition of penguin guano or seal excrement into tundra soils facilitated the simultaneous production of CH3Cl and CH3Br and resulted in a smaller sink in PCS, SCS, and PLS. Laboratory-based thermal treatments and anaerobic incubation experiments suggested that the consumption of CH3Cl and CH3Br was predominantly mediated by microbes while the production was abiotic and O2 independent. Temperature gradient incubations revealed that increasing soil temperature promoted the consumption of CH3Cl and CH3Br in UTS, suggesting that the regional sink may increase with Antarctic warming, depending on changes in soil moisture and abiotic production rates.
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Cloreto de Metila , Animais , Regiões Antárticas , Hidrocarbonetos Bromados , Cloreto de Metila/análise , Solo , TundraRESUMO
BACKGROUND: This study aims to investigate the molecular mechanism of Adenovirus type 36 (Ad36) in adipocyte differentiation and glucolipid metabolism. METHODS: Rat obesity model was established by Ad36 infection and high-fat diet, respectively. Comparison of the body weight, clinical biochemical indicators, insulin sensitivity and lipid heterotopic deposition between these two models was performed. Ad36-induced adipocyte in vitro model was also established. The binding rate of FoxO1, PPARγ and its target gene promoter was detected using ChIP. The mRNA and protein expression levels of PPARγ and downstream target genes were detected by RT-PCR and Western blot, respectively. Oil red O staining was used to measure differentiation into adipocyte. Wortmannin (WM), inhibitor of PI3K, was used to act on Ad36-induced hADSCs. RESULTS: Ad36-induced obese rats did not exhibit disorders in blood glucose and blood TG, insulin resistance and lipid ectopic deposition. The expression of Adipoq, Lpin1 and Glut4 in the adipose tissue increased. Oil red O staining showed that Ad36 induced the differentiation of hAMSCs into human adipocytes in vitro. During this process, the binding rate of FoxO1 and PPARγ promoter regions was weakened. However, the binding rate of the transcription factor PPARγ to its target genes Acc, Adipoq, Lpin1 and Glut4 was enhanced, and thus increased the protein expression of P-FoxO1, PPARγ2, ACC, LPIN1, GLUT4 and ADIPOQ. The PI3K inhibitor Wortmannin reduced the expression of P-Akt, P-FoxO1 and PPARγ2, thereby inhibiting adipogenesis of hADSC. CONCLUSION: Ad36 may promote fatty acid and triglyceride synthesis, and improve insulin sensitivity by affecting the PI3K/Akt/FoxO1/PPARγ signaling pathway.
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Tecido Adiposo/metabolismo , Obesidade/genética , PPAR gama/genética , Células-Tronco/citologia , Adipócitos/metabolismo , Adipócitos/virologia , Adiponectina/genética , Tecido Adiposo/citologia , Tecido Adiposo/virologia , Animais , Diferenciação Celular/genética , Dieta Hiperlipídica/efeitos adversos , Proteína Forkhead Box O1/genética , Regulação da Expressão Gênica no Desenvolvimento , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Humanos , Metabolismo dos Lipídeos/genética , Obesidade/metabolismo , Obesidade/patologia , Obesidade/virologia , Fosfatidato Fosfatase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/virologia , Wortmanina/administração & dosagemRESUMO
AIMS: To determine the role of lncRNA HOXA11-AS1 on adipocyte differentiation. METHODS: Human adipose-derived stem cells (hADSCs) were isolated from adipose tissues of patients and cultured in vitro, followed by knockdown of HOXA11-AS1. Then, adipocyte differentiation and expression of adipogenic-related genes (CEBP-α, DGAT2, CIDEC, and perilipin) were measured by RT-qPCR and Western blot. RESULTS: We demonstrated that knockdown of HOXA11-AS1 inhibited adipocyte differentiation, leading to suppression of adipogenic-related gene (CEBP-α, DGAT2, CIDEC, and perilipin) transcription, as well as decreased lipid accumulation in hADSCs. In addition, lncRNA HOXA11-AS1 was highly expressed in obese patients and significantly increased during the process of adipocyte differentiation. CONCLUSION: The results provide new insight into the molecular mechanism by which lncRNA HOXA11-AS1 is involved in adipogenesis and may have implications for the treatment of obesity and associated disorders.
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Adipócitos/metabolismo , Adipogenia , Tecido Adiposo/crescimento & desenvolvimento , Proteínas de Homeodomínio/metabolismo , Obesidade/metabolismo , RNA Longo não Codificante/metabolismo , Células-Tronco/fisiologia , Adipócitos/patologia , Tecido Adiposo/patologia , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos , Células-Tronco/patologiaRESUMO
The High Energy Photon Source (HEPS), a 6â GeV green-field diffraction-limited storage ring light source, will be built in Beijing, China. The HEPS design has been evolving for about ten years, and is now mostly finished and ready for construction. The storage ring is based on a modified hybrid seven-bend achromat (7BA) design, where bending magnets with reverse bending angles and longitudinal gradients are adopted to reach an ultralow natural emittance of 34.2â pm with a circumference of 1360.4â m. The central slice of the dipole in the middle of the modified hybrid 7BA, with flexible magnetic field, is used as the source of the bending-magnet beamline. Moreover, alternating high- and low-beta sections are specially designed to generate and deliver X-ray synchrotron radiation with high brightness of 5â ×â 1022â photons s-1 mm-2 mrad-2 (0.1% bandwidth)-1. Here, the HEPS storage ring design and solutions to the challenges inherent in this ultralow-emittance design are presented.
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Kinetics of non-enzymatic browning and loss of free amino acids during different storage temperature (4, 25, 37 °C) were investigated. Changes of browning degree (A420), color parameters, Vitamin C (Vc), free amino acids and 5-hydroxymethylfurfural (5-HMF) were analyzed to evaluate the non-enzymatic browning reactions, which were significantly affected by storage temperature. The lower temperature (4 °C) decreased the loss of Vc and the generation of 5-HMF, but induce the highest loss of serine. At the end of storage, loss of serine, alanine and aspartic acid were mainly lost. Results showed that zero-order kinetic model (R2 > 0.859), the first-order model (R2 > 0.926) and the combined kinetic model (R2 > 0.916) were the most appropriate to describe the changes of a* and b* values, the degradation of Vc and the changes of A420, L* and 5-HMF during different storage temperatures. These kinetic models can be applied for predicting and minimizing the non-enzymatic browning of fresh peach juice during storage.
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This study is to investigate the role of adenovirus 36 (Ad36) in regulating expression of peroxisome proliferator-activated receptor γ (PPARγ) and cell death-inducing DFFA-like effector c (CIDEC) in Ad36-induced adipocyte differentiation. Human adipose-derived mesenchymal stem cells (hAMSCs) were isolated and cultured, and then infected with Ad36. Ad36-induced adipocytes were identified using quantitative real-time PCR and Oil red O staining. The expression levels of PPARγ and CIDEC in Ad36-induced adipocytes were determined by quantitative real-time PCR and Western blot analysis. Glucose uptake and intracellular triglyceride content were also determined in these induced cells. Our results from the Oil red O staining showed that Ad36 induced the differentiation of hAMSCs into human adipocytes in vitro. Moreover, the medium glucose concentration was significantly decreased, while the intracellular triglyceride content was significantly increased, in the Ad36-induced adipocytes, compared with the control group. Furthermore, our results showed that, the mRNA and protein expression levels of PPARγ and CIDEC were significantly upregulated in Ad36-induced adipocytes, in a time-dependent manner. On the other hand, compared with the control group, the CIDEC expression was downregulated when the Ad36-induced adipocytes were treated with the PPARγ inhibitor, GW9662. Ad36 could upregulate the expression level of CIDEC through increasing PPARγ expression during the adipocyte differentiation process.
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Adenoviridae/fisiologia , Adipócitos/citologia , Células-Tronco Mesenquimais/virologia , PPAR gama/genética , Proteínas/genética , Adipócitos/metabolismo , Adipócitos/virologia , Anilidas/farmacologia , Proteínas Reguladoras de Apoptose , Diferenciação Celular , Células Cultivadas , Glucose/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , PPAR gama/metabolismo , Proteínas/metabolismo , Fatores de Tempo , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The purpose of this study was to gain insights into the variations in quality characteristics of white-flesh peach fruits. Eighteen cultivars of north of China were investigated. The quality evaluation indicators, including color, physico-chemical and nutritional attributes were measured. Analysis of variance revealed that all the indicators showed significant differences among the cultivars, except edible rate. Principal Component Analysis (PCA) conducted to distinguish the indicators among cultivars, suggested that the most important factors affecting the peach quality could be reduced into nine principal components. Crude fiber content, glucose content, peel-b*, TA, moisture content, pulp-firmness, quinic content, shikimic content and edible rate could be regarded as the characteristic indicators for PC1, PC2, PC3,PC4, PC5, PC6, PC7, PC8 and PC9, respectively. Cluster analysis classified the different cultivars into five main groups on the basis of the measured quality evaluation indicators, and the results were in good accordance with PCA results.
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An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.
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Povo Asiático/genética , Etnicidade/genética , Fácies , Receptores da Ectodisplasina/genética , População Branca/genética , Adolescente , Adulto , Alelos , China , Feminino , Humanos , Masculino , Fenótipo , Adulto JovemRESUMO
Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.67 × 10-16), accounting for 3.66 % of the total variance. The candidate gene approach did not find further significant associations, suggesting that hair straightness may be affected by a large number of genes with subtle effects. Notably, genetic variants associated with hair straightness in Europeans are generally low in frequency in Han Chinese, and vice versa. To evaluate the relative contribution of these variants, we performed a second genome-wide scan in 709 samples from the Uyghur, an admixed population with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 × 10-12) and TCHH (rs11803731: P = 1.46 × 10-3) are associated with hair straightness, but EDAR (OR 0.415) has a greater effect than TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P = 0.645), suggesting that these two genes affect hair straightness through different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not subject to selection. While EDAR is under strong selection in East Asia, it does not appear to be subject to selection after the admixture in Uyghurs. These suggest that hair straightness is unlikely a trait under selection.
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Antígenos/genética , Receptor Edar/genética , Estudo de Associação Genômica Ampla , Cabelo , Proteínas de Filamentos Intermediários/genética , Povo Asiático/genética , China , Feminino , Frequência do Gene , Predisposição Genética para Doença , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Cabelo/ultraestrutura , Haplótipos , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , População Branca/genéticaRESUMO
Molecules containing heteroatoms, such as Se and S, play an indispensable role in the discovery and design of pharmaceuticals, whereas Se has been less studied. Here, we described a photoredox strategy to synthesize C-benzoselenazolyl (Bs) glycosides from 2-isocyanoaryl selenoethers and glycosyl bromides. This reaction was carried out under mild conditions with high efficiency. C-Benzothiazolyl (Bt) glycosides could also be synthesized from 2-isocyanoaryl thioethers using this strategy. This method can access novel seleno/thiosugars, which will benefit Se/S-containing drug discovery.
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OBJECTIVE: This study was conducted to present a completely digital workflow for the fabrication of occlusal stabilization splints using CAD/CAM systems and a digital face bow based on optical sensor technology. METHODS: Digital scans of the maxillary and mandibular arches of 20 volunteers were obtained using an intraoral scanner. Jaw relation and mandibular movements were recorded with a digital face bow via optical sensors. The virtual increase of the vertical dimension of occlusion (VDO) was then performed, after which computer-aided design (CAD) of the occlusal stabilization splints was carried out. The corresponding splints were then manufactured using digitally controlled technology. RESULTS: A completely digital workflow for the manufacturing of occlusal stabilization splints was found to be clinically feasible. The corresponding data analysis revealed high congruence between virtual and physical occlusal contacts on the occlusal splint. Moreover, the appropriate guidance of the anterior teeth area was easily obtainable, and the time for adjusting the occlusion was less. CONCLUSIONS: This study demonstrated that the fabrication of occlusal stabilization splints using a fully digital workflow is feasible. Compared to traditional impression-based manufacturing, several advantages of digital manufacturing include easy accessibility, time-efficient manufacturing, high-level accuracy in splint quality, and potential to manufacture duplicate splints. CLINICAL SIGNIFICANCE: The proposed fully digital approach may help young dentists fabricating stable occlusal splints with beneficial curative effects. Meanwhile, it could also improve the production efficiency of stable occlusal splints, saving time for both doctors and patients while reducing labor costs.