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Background: The objective of this study was to investigate the correlation between the 7-joint ultrasound score (US7) and disease activity in patients with rheumatoid arthritis (RA). Methods: Forty-four patients with active RA were assessed, and the correlation between US7 and disease activity indicators such as the disease activity score (DAS28), rheumatoid factor (RF), the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was analyzed. In addition, the proportions of US7 points accounted for by different joint regions and joint surfaces were analyzed. Results: RF, CRP, and ESR were significantly increased in the RA group compared with the control group (P < 0.05). In the RA group, DAS28 (r = 0.0.561, P < 0.01), RF (r = 0.635, P < 0.01), ESR (r = 0.585, P < 0.01), and CRP (r = 0.492, P < 0.01) were positively correlated with US7. In terms of contributions to US7, the most susceptible joint surface is the dorsal surface, and the most susceptible joint area is the dorsal wrist. Conclusion: US7 is positively correlated with disease activity indicators of RA, which can objectively reflect disease activity in RA patients and provide a reference for clinical diagnosis and efficacy evaluation.
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Human activities have caused an imbalance in the input nitrogen and phosphorus (N/P) in the biosphere. The imbalance of N/P is one of the characteristics of water eutrophication, which is the fundamental factor responsible for the blooms. The effects of the N/P imbalance on diatom and phycospheric bacteria in blooms are poorly understood. In this study, the N/P molar ratio in real water (14:1) and the predicted N/P molar ratio in future water (65:1) were simulated to analyze the response of Cyclotella sp. and phycospheric bacteria to the N/P imbalance. The results showed that the N/P imbalance inhibited the growth of Cyclotella sp., but prolonged diatom bloom duration. The resistance of Cyclotella sp. to the N/P imbalance is related to phycospheric bacteria, and there are dynamic regulatory mechanisms within the phycospheric bacteria community to resist the N/P imbalance: (1) the increase of HNA bacterial density, the decrease of LNA bacterial density, (2) the increase of phycospheric bacterial diversity and eutrophic bacteria abundance, and the change of denitrifying bacteria abundance, (3) the activity of nitrogen and phosphorus metabolism of HNA bacteria enhanced, while that of LNA bacteria decreased. And the gene hosts of nitrogen and phosphorus metabolism were most enriched in Proteobacteria, indicating that Proteobacteria played an important role in maintaining the stability of phycospheric bacteria and was the dominant phylum resistant to the N/P imbalance. This study clarified that the algal-bacteria system was resistant to the N/P imbalance and implied that the N/P imbalance had little effect on the occurrence of diatom bloom events due to the presence of phycospheric bacteria.
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Bacterias , Diatomeas , Eutrofización , Nitrógeno , Fósforo , Nitrógeno/metabolismoRESUMEN
In recent years, micro/nanoplastics have garnered widespread attention due to their ecological risks. In this study, we investigated the effects of polystyrene nanoparticles (PS-NPs) of different sizes on the growth and biofilm formation of Pseudomonas aeruginosa PAO1. The results demonstrated that exposure to certain concentrations of PS-NPs significantly promoted bacterial biofilm formation. Meanwhile, we comprehensively revealed its mechanism whereby PS-NPs induced oxidative stress and altered bacterial membrane permeability by contacting or penetrating bacterial membranes. To counteract the stimulation by PS-NPs and reduce their toxicity, bacteria enhanced biofilm formation by upregulating the expression of biofilm-related genes, increasing EPS and virulence factors secretion, and enhancing bacterial motility through the participation of the quorum sensing (QS) system. Additionally, we also found that exposure to PS-NPs enhanced bacterial antibiotic resistance, posing a challenge to antimicrobial therapy. Our study reveals the toxic effects of nanoplastics and the defense mechanisms of bacteria, which has important implications for the risk assessment and management of environmental nanoplastics.
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Nanopartículas , Pseudomonas aeruginosa , Poliestirenos/toxicidad , Microplásticos/farmacología , Biopelículas , Percepción de Quorum , Nanopartículas/toxicidad , Bacterias , Antibacterianos/toxicidadRESUMEN
We investigated the geographical and environmental distance-decay relationships for both of the two bacteria in the Haihe River, Tianjin, China. HNA bacteria exhibited a stronger geographical variation-dependent pattern while LNA bacteria exhibited a stronger environmental variation-dependent pattern. Variance partition analysis (VPA), Mantel test, and partial mantel test validated the discrepant impacts of geographical distance and environmental factors on their two communities. The heterogeneous selection dominated community assembly of LNA bacteria demonstrates their greater sensitivity to environmental conditions. As the deterministic environmental factor, anthropogenic original dissolved organic matter (DOM) functions exclusively on LNA bacteria, and it is the critical factor leading to the discrepant biogeographical patterns of LNA and HNA bacteria. LNA bacteria interact with HNA bacteria and mediate the DOM driving total bacteria assembly. The LNA keystone taxa, Pseudomonas, Rheinheimera, Candidatus Aquiluna, and hgcl clade are capable to compete with HNA bacteria for anthropogenic original DOM, and are potential indicators of anthropogenic pollution. Our research reveals the non-negligible effect of the LNA bacteria in regulating the ecological response of total bacteria.
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Materia Orgánica Disuelta , Ríos , Ríos/microbiología , Bacterias , Geografía , ChinaRESUMEN
Background: Testicular torsion is an acute scrotal disorder requiring immediate emergency treatment. Ischemic injury and reperfusion injury are important causes of oxidative stress and irreversible oxidative damage after testicular torsion. Although a large number of literatures have discussed the causes and treatment of testicular torsion, there is currently a lack of systematic exploration of the historical evolution of testicular torsion and the construction of a knowledge framework. Method: The Web of Science Core Collection was searched for studies on testicular torsion published between 2000 and 2022. The basic data of the literature were analyzed by using Excel and CiteSpace software. Result: A total of 1,007 publications on testicular torsion published were found in 64 countries between 2000 and 2022, with an increasing annual publication level. Early detection, early diagnosis and early treatment of testicular torsion had always been at the core of clinical practice, and the pathological cascade reaction of ischemic injury and ischemia-reperfusion injury after testicular torsion were also at the core of basic research. Emphasis had been placed on the development of protective drugs for ischemia and reperfusion after testicular torsion in various countries, regions and institutions. Conclusion: Over the past 20 years, the research on testicular torsion had been widely concerned. Hot topics in testicular torsion in recent years were ischemia-reperfusion injury, oxidative stress, rat, doppler ultrasonography, diagnosis and orchiectomy. This article may provide a useful resource for clinicians and basic researchers regarding testicular torsion.
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Dynamic regulation of intestinal epithelial cell (IEC) proliferation and differentiation is crucial for maintaining mucosa homeostasis and the response to helminth infection. O-GlcNAc transferase (OGT), an enzyme catalyzing the transfer of GlcNAc from the donor substrate UDP-GlcNAc onto acceptor proteins, has been proposed to promote intestinal epithelial remodeling for helminth expulsion by modifying and activating epithelial STAT6, but whether the IEC intrinsic OGT-STAT6 axis is involved in anti-helminth responses has not been tested in vivo. Here, we show that the inducible deletion of Ogt in IECs of adult mice leads to reduced tuft and goblet cell differentiation, increased crypt cell proliferation, and aberrant Paneth cell localization. By using a mouse model with concurrent Ogt deletion and STAT6 overexpression in IECs, we provide direct in vivo evidence that STAT6 acts downstream of OGT to control tuft and goblet cell differentiation in IECs. However, epithelial OGT regulates crypt cell proliferation and Paneth cell differentiation in a STAT6-independent pathway. Our results verify that protein O-GlcNAcylation in IECs is crucial for maintaining epithelial homeostasis and anti-helminthic type 2 immune responses.
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Mebendazol , N-Acetilglucosaminiltransferasas , Células Caliciformes/metabolismo , Intestinos , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/metabolismo , Células de Paneth/metabolismo , Uridina DifosfatoRESUMEN
Dynamic regulation of intestinal epithelial cell (IEC) differentiation is crucial for both homeostasis and the response to helminth infection. SIRT6 belongs to the NAD+-dependent deacetylases and has established diverse roles in aging, metabolism and disease. Here, we report that IEC Sirt6 deletion leads to impaired tuft cell development and type 2 immunity in response to helminth infection, thereby resulting in compromised worm expulsion. Conversely, after helminth infection, IEC SIRT6 transgenic mice exhibit enhanced epithelial remodeling process and more efficient worm clearance. Mechanistically, Sirt6 ablation causes elevated Socs3 expression, and subsequently attenuated tyrosine 641 phosphorylation of STAT6 in IECs. Notably, intestinal epithelial overexpression of constitutively activated STAT6 (STAT6vt) in mice is sufficient to induce the expansion of tuft and goblet cell linage. Furthermore, epithelial STAT6vt overexpression remarkedly reverses the defects in intestinal epithelial remodeling caused by Sirt6 ablation. Our results reveal a novel function of SIRT6 in regulating intestinal epithelial remodeling and mucosal type 2 immunity in response to helminth infection.
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Helmintiasis/inmunología , Mucosa Intestinal , Factor de Transcripción STAT6/metabolismo , Sirtuinas/metabolismo , Animales , Células Epiteliales/metabolismo , Células Caliciformes/metabolismo , Helmintiasis/metabolismo , Inmunidad Mucosa , Mucosa Intestinal/metabolismo , Intestinos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Factor de Transcripción STAT6/genética , Sirtuinas/genéticaRESUMEN
Objective: The aim of the study is to explore the relationship between the degree of illness in elderly patients with rheumatoid arthritis (RA) and parameters of musculoskeletal ultrasound (MSUS) and Oswestry Dysfunction Index (ODI) and its clinical value. Methods: The clinical data of 100 elderly patients with RA admitted to our hospital from May 2016 to May 2022 were retrospectively analyzed. The patients were divided into four groups, including the remission group (DAS28 ≤ 2.6, n = 25), low activity group (2.6 ≤ DAS28 ≤ 3.2, n = 25), middle activity group (3.2 ≤ DAS28 ≤ 5.1, n = 25), and high activity group (DAS > 5.1, n = 25) according to the disease activity score-28 (DAS28). All patients underwent ultrasonic detection to compare the relationship between the degree of illness in elderly patients with RA and parameters of MSUS and ODI. Results: The total semiquantitative score of MSUS and ODI score in the remission group were obviously lower than those in the other three groups (P < 0.001). The degree of illness in elderly patients with RA was positively correlated with parameters of MSUS (r = 0.886, P < 0.001). The degree of illness in elderly patients with RA was positively correlated with ODI (r = 0.907, P < 0.001). Conclusion: The degree of illness in elderly patients with RA is closely related to parameters of MSUS and ODI, and the parameters of MSUS have a higher evaluation value for the degree of illness in elderly patients with RA, which are correlated with ODI.
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Extracting features of retinal vessels from fundus images plays an essential role in computer-aided diagnosis of diseases, such as diabetes, hypertension, and cerebrovascular diseases. Although a number of deep learning-based methods have been used in this field, the accuracy of retinal vessel segmentation remains challenging due to limited densely annotated data, inter-vessel differences, and structured prediction problems, especially in areas of small blood vessels and the optic disk. In this paper, we propose an ARN model with a atrous block to address these issues, which can avoid the loss of data structure, and enlarge the receptive field, so that each convolution output contains a larger range of information. In addition, we also introduce residual convolution network to increase the network depth and improve the network performance.Some key parameters are used to measure the feasibility of the model, such as sensitivity (Se), specificity (Sp), F1-score (F1), accuracy (Acc), and area under each curve (AUC). Experimental results on two benchmark datasets demonstrate the effectiveness of the proposed methods, which accuracy are 0.9686 on the DRIVE and 0.9746 on the CHASE DB1. The segmentation structure can assist the doctor in diagnosis more effectively.
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Algoritmos , Redes Neurales de la Computación , Diagnóstico por Computador/métodos , Progresión de la Enfermedad , Fondo de Ojo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Vasos Retinianos/diagnóstico por imagenRESUMEN
OBJECTIVE: Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model. METHODS: A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay. RESULTS: It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1ß, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance. CONCLUSION: Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.
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Artritis Experimental , Artritis Reumatoide , MicroARNs , Moxibustión , Animales , Artritis Experimental/genética , Artritis Experimental/patología , Artritis Experimental/terapia , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Artritis Reumatoide/terapia , Citocinas , Modelos Animales de Enfermedad , Interleucina-10 , Interleucina-17 , Interleucina-6 , Masculino , Ratones , Ratones Endogámicos DBA , MicroARNs/genética , Linfocitos T Reguladores , Células Th17/metabolismo , Células Th17/patología , Factor de Necrosis Tumoral alfaRESUMEN
Objective: To evaluate the clinical efficacy of acupoint catgut embedding in the treatment of simple obesity through network meta-analysis. Methods: PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP database (VIP) were searched by using computer from 2011 to August 2021, and 35 RCT studies were retrieved. The quality of the literature was evaluated using the modified Jadad scoring table, and Stata 15.0 software was used for traditional meta-analysis and network meta-analysis. Results: Thirty-five RCTs (3040 cases in total) were included. Acupoint embedding, acupuncture, electroacupuncture, TCM, acupoint embedding + acupuncture, acupoint embedding + exercise diet therapy, acupoint embedding + TCM, exercise diet therapy, acupoint embedding + moxibustion, and acupoint embedding + cupping were investigated in the studies. The results of network meta-analysis were as follows: in terms of total effective rate, acupoint catgut embedding was superior to acupuncture, electroacupuncture, and exercise diet therapy (P < 0.05); electroacupuncture, acupoint catgut embedding + acupuncture, acupoint catgut embedding + exercise diet therapy, acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to acupuncture (P < 0.05); acupoint catgut + moxibustion was superior to electroacupuncture (P < 0.05); acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to TCM treatment (P < 0.05); and electroacupuncture, acupoint catgut, acupoint catgut + acupuncture, acupoint catgut + exercise diet therapy, acupoint catgut + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to sports diet therapy (P < 0.05). Regarding weight loss, acupuncture treatment was superior to acupoint catgut embedding therapy (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to acupuncture and electroacupuncture treatment (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, and acupoint catgut embedding + moxibustion were superior to TCM treatment (P < 0.05); and acupoint catgut embedding, acupoint catgut embedding + acupuncture, catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to exercise diet therapy (P < 0.05). In terms of BMI reduction, acupoint catgut embedding + moxibustion and acupoint catgut embedding + cupping were more evident than acupuncture treatment (P < 0.05); and acupoint catgut embedding + moxibustion was more evident than electroacupuncture treatment (P < 0.05). Conclusion: Acupoint catgut embedding and its combination with other therapies are the first choice for the treatment of simple obesity.
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The mechanistic target of rapamycin complex 1 (mTORC1) acts as a central regulator of metabolic pathways that drive cellular growth. Abnormal activation of mTORC1 occurs at high frequency in human and mouse hepatocellular carcinoma (HCC). DEP domain-containing protein 5 (DEPDC5), a component of GATOR1 complex, is a repressor of amino acid-sensing branch of the mTORC1 pathway. In the current study, we found that persistent activation of hepatic mTORC1 signaling caused by Depdc5 ablation was sufficient to induce a pathological program of liver damage, inflammation and fibrosis that triggers spontaneous HCC development. Take advantage of the combinatory treatment with a single dose of diethylnitrosamine (DEN) and chronic feeding with high-fat diet (HFD), we demonstrated that hepatic depdc5 deletion did not aggravate DEN&HFD induced liver tumorigenesis, probably due to its protective effects on diet-induced liver steatosis. In addition, we further showed that chronic rapamycin treatment did not have any apparent tumor-suppressing effects on DEN&HFD treated control mice, whereas it dramatically reduced the tumor burden in mice with hepatic Depdc5 ablation. This study provides the novel in vivo evidence for Depdc5 deletion mediated mTORC1 hyperactivation in liver tumorigenesis caused by aging or DEN&HFD treatment. Moreover, our findings also propose that pharmacological inhibition of mTORC1 signaling maybe a promising strategy to treat HCC patients with mutations in DEPDC5 gene.
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Carcinoma Hepatocelular/patología , Dieta Alta en Grasa , Dietilnitrosamina/toxicidad , Hígado Graso/patología , Proteínas Activadoras de GTPasa/fisiología , Hígado/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Alquilantes/toxicidad , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Modelos Animales de Enfermedad , Hígado Graso/inducido químicamente , Hígado Graso/genética , Hígado Graso/metabolismo , Femenino , Inflamación/inmunología , Inflamación/metabolismo , Hígado/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal , Carga TumoralRESUMEN
The mammalian target of rapamycin complex 1 (mTORC1) is a crucial regulator of adipogenesis and systemic energy metabolism. Its dysregulation leads to a diversity of metabolic diseases, including obesity and type 2 diabetes. DEP-domain containing 5 (DEPDC5) is a critical component of GATOR1 complex that functions as a key inhibitor of mTORC1. So far, its function in adipose tissue remains largely unknown. Herein we evaluated how persistent mTORC1 activation in adipocyte via Depdc5 knockout modulates adiposity in vivo. Our data indicated that adipocyte-specific knockout of Depdc5 in aged mice led to reduced visceral fat, aggravated insulin resistance and enhanced adipose tissue inflammation. Moreover, we found that Depdc5 ablation resulted in upregulation of adipose triglyceride lipase (ATGL) in adipocytes and elevated levels of serum free fatty acids (FFAs). Intriguingly, rapamycin treatment did not reverse insulin resistance but alleviated adipose tissue inflammation caused by Depdc5 deletion. Taken together, our findings revealed that mTORC1 activation caused by Depdc5 deletion promotes lipolysis process and further exacerbates insulin resistance and adipose tissue inflammation in mice.
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Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Proteínas Activadoras de GTPasa/genética , Inflamación/genética , Resistencia a la Insulina/genética , Adipogénesis/genética , Tejido Adiposo/patología , Factores de Edad , Animales , Western Blotting , Dieta Alta en Grasa/efectos adversos , Proteínas Activadoras de GTPasa/deficiencia , Inflamación/metabolismo , Grasa Intraabdominal/metabolismo , Lipasa/genética , Lipasa/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones Noqueados , Ratones Transgénicos , Obesidad/etiología , Obesidad/genética , Obesidad/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genéticaRESUMEN
Feature pyramid network (FPN) based models, which fuse the semantics and salient details in a progressive manner, have been proven highly effective in salient object detection. However, it is observed that these models often generate saliency maps with incomplete object structures or unclear object boundaries, due to the indirect information propagation among distant layers that makes such fusion structure less effective. In this work, we propose a novel Cross-layer Feature Pyramid Network (CFPN), in which direct cross-layer communication is enabled to improve the progressive fusion in salient object detection. Specifically, the proposed network first aggregates multi-scale features from different layers into feature maps that have access to both the high- and low- level information. Then, it distributes the aggregated features to all the involved layers to gain access to richer context. In this way, the distributed features per layer own both semantics and salient details from all other layers simultaneously, and suffer reduced loss of important information during the progressive feature fusion. At last, CFPN fuses the distributed features of each layer stage-by-stage. This way, the high-level features that contain context useful for locating complete objects are preserved until the final output layer, and the low-level features that contain spatial structure details are embedded into each layer to preserve spatial structural details. Extensive experimental results over six widely used salient object detection benchmarks and with three popular backbones clearly demonstrate that CFPN can accurately locate fairly complete salient regions and effectively segment the object boundaries.
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The mechanism underlying the relationship between autistic traits and social anxiety still remains unknown. It is therefore necessary to investigate potential psychological and biological mechanisms. A total of 2695 college students were samples for this research during 2017-2018. The assessed variables included demographic characteristics and measures of autistic traits, sense of security, coping styles, and social anxiety. Blood samples were collected from which DNA was extracted. Regression analysis indicated that autistic traits and negative coping were positively associated with social anxiety; furthermore, positive coping, interpersonal security, and sense of control were negatively associated with social anxiety. Further analyses demonstrated that the relationship between autistic traits and social anxiety was mediated by coping styles (both positive coping and negative coping) and sense of security (both interpersonal security and sense of control), and coping style predicted the sense of security. The FK506 binding protein 5 (FKBP5) gene rs3800373 moderated the association between autistic traits and social anxiety. The present study is the first to demonstrate that both coping style and sense of security play an intermediate role between autistic traits and social anxiety in a sample of Chinese college students; moreover, the FKBP5 gene moderates this association between autistic traits and social anxiety.
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Adaptación Psicológica , Ansiedad/genética , Trastorno Autístico/genética , Ajuste Emocional , Proteínas de Unión a Tacrolimus/genética , Adolescente , Ansiedad/psicología , Trastorno Autístico/psicología , Femenino , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Encuestas y CuestionariosRESUMEN
Aims: Long non-coding RNA IRAIN (lncRNA IRAIN) plays a critical role in numerous malignancies. However, the function of lncRNA IRAIN in renal carcinoma (RC) remains enigmatic. The purpose of this study is to characterize the effects of lncRNA IRAIN on RC progression. Methods: The expression pattern of lncRNA IRAIN and the vascular endothelial growth factor A (VEGFA) in RC tissues and cells was characterized by RT-qPCR and Western blot analysis. The roles of lncRNA IRAIN and VEGFA in the progression of RC were studied by gain- or loss-of-function experiments. Bioinformatics data analysis was used to predict CpG islands in the VEGFA promoter region. MSP was applied to detect the level of DNA methylation in RC cells. The interaction between lncRNA IRAIN and VEGFA was identified by RNA immunoprecipitation and RNA-protein pull down assays. Recruitment of DNA methyltransferases (Dnmt) to the VEGFA promoter region was achieved by chromatin immunoprecipitation. The subcellular localization of lncRNA IRAIN was detected by fractionation of nuclear and cytoplasmic RNA. Cell viability was investigated by CCK-8 assay, cell migration was tested by transwell migration assay, and apoptosis was analyzed by flow cytometry. The expression of epithelial-mesenchymal transition-related and apoptotic factors was evaluated by Western blot analysis. Finally, the effect of the lncRNA IRAIN/VEGFA axis was confirmed in an in vivo tumor xenograft model. Results: LncRNA IRAIN was poorly expressed in RC tissues and cells with a primary localization in the nucleus, while VEGFA was highly expressed. Overexpression of lncRNA IRAIN or knockdown of VEGFA inhibited cell proliferation and migration and induced the apoptosis of RC cells. Bioinformatics analysis indicated the presence of CpG islands in the VEGFA promoter region. Lack of methylation at specific sites in the VEGFA promoter region was detected through MSP assay. We found that lncRNA IRAIN was able to inhibit VEGFA expression through recruitment of Dnmt1, Dnmt3a, and Dnmt3b to the VEGFA promoter region. LncRNA IRAIN was also able to suppress RC tumor growth via repression of VEGFA in an in vivo mouse xenograft model. Conclusion: Our data shows that by downregulating VEGFA expression in RC, the lncRNA IRAIN has tumor-suppressive potential.
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Iron (Fe) is a major micronutrient which influences plant growth, development, quality and yield. Although basic helix-loop-helix (bHLH) transcription factors (TFs) which respond to iron deficiency have been identified, the molecular mechanisms have not been fully elucidated. In this study, a novel bHLH TF, NtbHLH1, was found to be induced by iron deficiency. Further analysis indicated that NtbHLH1 is localized to the nucleus and functions as a transcriptional activator. Moreover, overexpression of NtbHLH1 resulted in longer roots, altered rhizosphere pH and increased ferric-chelate reductase activity in iron deficient conditions. Overall these changes resulted in increased iron uptake relative to wild type plants. NtbHLH1 mutants, on the other hand, had an opposite phenotype. In addition, transcript levels of seven genes associated with iron deficiency response were higher in the NtbHLH1 overexpression transgenic plants and lower in ntbhlh1 relative to the WT under iron deficiency treatment. Taken together, these results demonstrated that NtbHLH1 plays a key role in iron deficiency response and they provide new insights into the molecular basis of iron homeostasis in tobacco.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Regulación de la Expresión Génica de las Plantas , Hierro/metabolismo , Nicotiana/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Homeostasis , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Nicotiana/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: MicroRNAs (miRNAs) are well characterized for their important roles in human cancers by influencing various aspects of malignancy. Till now, the function and mechanism of miR-204, a tumor suppressor in several cancers, remain unclear in bladder cancer (BC). Here, we intend to explore its roles in BC progression. METHODS: qRT-PCR was applied to determine miR-204 and ROBO4 expression in BC tissues and cell lines. miR-204 expression with clinicopathological features was analyzed. The impacts of miR-204 on BC cell growth and metastasis in vitro were evaluated by both loss-of-function and gain-of-function assays (CCK-8, crystal violet staining, wound healing and transwell assays). Furthermore, qRT-PCR, Western blot and luciferase reporter assays were used to validate the targeting of ROBO4 by miR-204. Finally, linear regression was performed to analyze the correlation of miR-204 and ROBO4 in BC tissues. RESULTS: Expression of miR-204 was markedly decreased in BC tissues and cell lines were compared with respective controls. Low miR-204 expression was associated with positive advanced T stage and lymph node metastasis. Cellular function studies revealed that miR-204 inhibited BC cell growth, migration and invasion. Mechanistic exploration found that miR-204 directly targeted ROBO4. Rescue assays indicated that ROBO4 restoration could reverse the antitumor effects of miR-204 in BC. Finally, ROBO4 was significantly correlated with miR-204 levels inversely. CONCLUSION: miR-204 might serve as a tumor suppressor in BC by targeting ROBO4.
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Childhood maltreatment (CM) is a factor of risk for psychosis and is associated with alterations in facial emotion processing.Negative symptoms of schizophrenia-spectrum disorders are associated with deficits in facial emotion processing, but research findings on schizotypy are mixed. This study examined the early stage of facial emotion processing in young adults with high levels of negative schizotypy (NS) and explored the impact of childhood maltreatment. On the basis of the Social and Physical Anhedonia subscales of the Chapman Psychosis-Proneness Scales, a total of 74 high-NS and 52 low-NS individuals were recruited to complete the Childhood Trauma Questionnaire and the dot-probe task. The P100 and N170 components of event-related potentials were measured to assess the processing of four facial expressions of emotion. The high-NS group showed significantly reduced P100 amplitudes for all facial expressions. Angry and fearful expressions elicited larger N170 amplitudes than disgusted and happy expressions. Happy expressions elicited shorter N170 latencies than disgusted expressions. Compared to the high-NS group without CM, the high-NS group with CM had a longer latency of P100. Individuals with high NS, compared to individuals with low NS, have impaired fundamental visual processing, but intact processing of facial figurations. Childhood maltreatment may be a factor responsible for the pathological state of the visual pathway in high NS group.
Asunto(s)
Maltrato a los Niños/psicología , Emociones/fisiología , Expresión Facial , Trastorno de la Personalidad Esquizotípica/psicología , Adolescente , Adultos Sobrevivientes del Maltrato a los Niños/psicología , Anhedonia , Niño , Estudios Transversales , Electroencefalografía , Potenciales Evocados , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The utility of superb microvascular imaging (SMI) for evaluating hand joint lesions in patients with rheumatoid arthritis (RA) in clinical remission is unreported. This study aimed to compare SMI and power Doppler imaging (PDI) for the evaluation of hand joint lesions in these patients. Twenty-six patients with RA in clinical remission were enrolled. A total of 572 joints (52 wrist, 260 proximal interphalangeal, and 260 metacarpophalangeal joints) were detected by SMI and PDI. A semi-quantitative scale of 0-3 was used to compare the detection of synovial blood flow signal by SMI and PDI. Inter-observer agreement for the assessment of SMI and PDI scores was measured with kappa values. In the ten healthy volunteers, SMI and PDI signals were both scored 0. In the 26 RA patients, the remission rate via PDI was 65.4% but was only 42.3% via SMI. SMI also detected microvessel flow signal in seven patients diagnosed with clinical remission via PDI. Moreover, a total of 106 blood flow signals (18.5%) were detected by SMI, while 50 blood flow signals (8.7%) were detected by PDI. Compared with PDI, SMI increased 18.0% of power flow signals from Grade 0-1 and increased 13.7% of power flow signals from Grade 1-2. One joint classified as Grade 1 by PDI was classified as Grade 0 by SMI. Inter-observer agreement for PDI and SMI semi-quantitative scoring was moderate (kappa = 0.463). SMI seems more sensitive than PDI for detecting hand joint lesions in RA in clinical remission PDI, and could aid the achievement of true remission in RA patients.