Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
1.
Blood Purif ; 53(10): 813-823, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39089231

RESUMEN

INTRODUCTION: Autogenous arteriovenous fistula (AVF) is the preferred vascular access in patients undergoing maintenance hemodialysis (MHD). However, complications such as thrombosis may occur. This study aimed to construct and validate a machine learning-based risk-prediction model for AVF thrombosis, hypothesizing that such a model can effectively predict occurrences, providing a foundation for early clinical intervention. METHODS: The retrospective longitudinal study included a total of 270 patients who underwent MHD at the Hemodialysis Center of the Second Affiliated Hospital of Harbin Medical University between March 2021 and December 2022. During this study, baseline data and scale information of patients between March 2020 and December 2021 were collected. We recorded outcome indicators between March 2021 and December 2022 for subsequent analyses. Five machine learning models were developed (artificial neural network, logistic regression, ridge classification, random forest, and adaptive boosting). The sensitivity (recall), specificity, accuracy, and precision of each model were evaluated. The effect size of each variable was analyzed and ranked. Models were assessed using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: Among the 270 included patients, 105 had AVF thrombosis (55 male and 50 female patients; age range, 29-79 years; mean age, 56.72 years; standard deviation [SDs], ±13.10 years). Conversely, 165 patients did not have AVF thrombosis (99 male and 66 female patients; age range, 23-79 years; mean age, 53.58 years; SD, ± 13.33 years). During the observation period, approximately 52.6% of patients with AVF experienced long-term complications. The most common complications associated with AVF were thrombosis (105; 38.9%), aneurysm formation (27; 10%), and excessively high output flow (10; 3.7%). Fifty-four (20%) patients with AVF required intervention because of complications associated with vascular access. The AUROC curve of the testing set was between 0.858 and 0.903. CONCLUSION: In this study, we developed five machine learning models to predict the risk of AVF thrombosis, providing a reference for early clinical intervention.


Asunto(s)
Aprendizaje Automático , Diálisis Renal , Trombosis , Humanos , Diálisis Renal/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Trombosis/etiología , Anciano , Adulto , Estudios Retrospectivos , Derivación Arteriovenosa Quirúrgica/efectos adversos , Estudios Longitudinales , Factores de Riesgo , Medición de Riesgo , Curva ROC
2.
Microbiol Immunol ; 68(9): 305-330, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38961765

RESUMEN

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.


Asunto(s)
COVID-19 , Filogenia , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2/genética , Humanos , COVID-19/virología , Animales , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , Antivirales/farmacología , Chlorocebus aethiops , Células Vero , Microscopía por Crioelectrón , Ratones
3.
IEEE J Biomed Health Inform ; 28(5): 2916-2929, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38437146

RESUMEN

In recent years, 4D medical image involving structural and motion information of tissue has attracted increasing attention. The key to the 4D image reconstruction is to stack the 2D slices based on matching the aligned motion states. In this study, the distribution of the 2D slices with the different motion states is modeled as a manifold graph, and the reconstruction is turned to be the graph alignment. An embedding-alignment fusion-based graph convolution network (GCN) with a mixed-learning strategy is proposed to align the graphs. Herein, the embedding and alignment processes of graphs interact with each other to realize a precise alignment with retaining the manifold distribution. The mixed strategy of self- and semi-supervised learning makes the alignment sparse to avoid the mismatching caused by outliers in the graph. In the experiment, the proposed 4D reconstruction approach is validated on the different modalities including Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasound (US). We evaluate the reconstruction accuracy and compare it with those of state-of-the-art methods. The experiment results demonstrate that our approach can reconstruct a more accurate 4D image.


Asunto(s)
Algoritmos , Imagenología Tridimensional , Humanos , Imagenología Tridimensional/métodos , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Ultrasonografía/métodos , Aprendizaje Automático
4.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474317

RESUMEN

The BRI1 EMS suppressor 1(BES1) transcription factor is a crucial regulator in the signaling pathway of Brassinosteroid (BR) and plays an important role in plant growth and response to abiotic stress. Although the identification and functional validation of BES1 genes have been extensively explored in various plant species, the understanding of their role in woody plants-particularly the endangered species Phoebe bournei (Hemsl.) Yang-remains limited. In this study, we identified nine members of the BES1 gene family in the genome of P. bournei; these nine members were unevenly distributed across four chromosomes. In our further evolutionary analysis of PbBES1, we discovered that PbBES1 can be divided into three subfamilies (Class I, Class II, and Class IV) based on the evolutionary tree constructed with Arabidopsis thaliana, Oryza sativa, and Solanum lycopersicum. Each subfamily contains 2-5 PbBES1 genes. There were nine pairs of homologous BES1 genes in the synteny analysis of PbBES1 and AtBES1. Three segmental replication events and one pair of tandem duplication events were present among the PbBES1 family members. Additionally, we conducted promoter cis-acting element analysis and discovered that PbBES1 contains binding sites for plant growth and development, cell cycle regulation, and response to abiotic stress. PbBES1.2 is highly expressed in root bark, stem bark, root xylem, and stem xylem. PbBES1.3 was expressed in five tissues. Moreover, we examined the expression profiles of five representative PbBES1 genes under heat and drought stress. These experiments preliminarily verified their responsiveness and functional roles in mediating responses to abiotic stress. This study provides important clues to elucidate the functional characteristics of the BES1 gene family, and at the same time provides new insights and valuable information for the regulation of resistance in P. bournei.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Brasinoesteroides/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas/genética , Familia de Multigenes , Proteínas de Unión al ADN/metabolismo
5.
Plants (Basel) ; 13(5)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38475568

RESUMEN

Uridine diphosphate glycosyltransferases (UDP-GTs, UGTs), which are regulated by UGT genes, play a crucial role in glycosylation. In vivo, the activity of UGT genes can affect the availability of metabolites and the rate at which they can be eliminated from the body. UGT genes can exert their regulatory effects through mechanisms such as post-transcriptional modification, substrate subtype specificity, and drug interactions. Phoebe bournei is an economically significant tree species that is endemic to southern China. Despite extensive studies on the UGT gene family in various species, a comprehensive investigation of the UGT family in P. bournei has not been reported. Therefore, we conducted a systematic analysis to identify 156 UGT genes within the entire P. bournei genome, all of which contained the PSPG box. The PbUGT family consists of 14 subfamilies, consistent with Arabidopsis thaliana. We observed varying expression levels of PbUGT genes across different tissues in P. bournei, with the following average expression hierarchy: leaf > stem xylem > stem bark > root xylem > root bark. Covariance analysis revealed stronger covariance between P. bournei and closely related species. In addition, we stressed the seedlings with 10% NaCl and 10% PEG-6000. The PbUGT genes exhibited differential expression under drought and salt stresses, with specific expression patterns observed under each stress condition. Our findings shed light on the transcriptional response of PbUGT factors to drought and salt stresses, thereby establishing a foundation for future investigations into the role of PbUGT transcription factors.

6.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338732

RESUMEN

PIN-formed (PIN) proteins-specific transcription factors that are widely distributed in plants-play a pivotal role in regulating polar auxin transport, thus influencing plant growth, development, and abiotic stress responses. Although the identification and functional validation of PIN genes have been extensively explored in various plant species, their understanding in woody plants-particularly the endangered species Phoebe bournei (Hemsl.) Yang-remains limited. P. bournei is an economically significant tree species that is endemic to southern China. For this study, we employed bioinformatics approaches to screen and identify 13 members of the PIN gene family in P. bournei. Through a phylogenetic analysis, we classified these genes into five sub-families: A, B, C, D, and E. Furthermore, we conducted a comprehensive analysis of the physicochemical properties, three-dimensional structures, conserved motifs, and gene structures of the PbPIN proteins. Our results demonstrate that all PbPIN genes consist of exons and introns, albeit with variations in their number and length, highlighting the conservation and evolutionary changes in PbPIN genes. The results of our collinearity analysis indicate that the expansion of the PbPIN gene family primarily occurred through segmental duplication. Additionally, by predicting cis-acting elements in their promoters, we inferred the potential involvement of PbPIN genes in plant hormone and abiotic stress responses. To investigate their expression patterns, we conducted a comprehensive expression profiling of PbPIN genes in different tissues. Notably, we observed differential expression levels of PbPINs across the various tissues. Moreover, we examined the expression profiles of five representative PbPIN genes under abiotic stress conditions, including heat, cold, salt, and drought stress. These experiments preliminarily verified their responsiveness and functional roles in mediating responses to abiotic stress. In summary, this study systematically analyzes the expression patterns of PIN genes and their response to abiotic stresses in P. bournei using whole-genome data. Our findings provide novel insights and valuable information for stress tolerance regulation in P. bournei. Moreover, the study offers significant contributions towards unraveling the functional characteristics of the PIN gene family.


Asunto(s)
Proteínas de Plantas , Estrés Fisiológico , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Reguladores del Crecimiento de las Plantas , Intrones/genética , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Perfilación de la Expresión Génica/métodos , Genoma de Planta
7.
Nurs Crit Care ; 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37699863

RESUMEN

BACKGROUND: Postintensive care syndrome (PICS) has adverse multidimensional effects on nearly half of the patients discharged from ICU. Mental disorders such as anxiety, depression and post-traumatic stress disorder (PTSD) are the most common psychological problems for patients with PICS with harmful complications. However, developing prediction models for mental disorders in post-ICU patients is an understudied problem. AIMS: To explore the risk factors of PICS mental disorders, establish the prediction model and verify its prediction efficiency. STUDY DESIGN: In this cohort study, data were collected from 393 patients hospitalized in the ICU of a tertiary hospital from April to September 2022. Participants were randomly assigned to modelling and validation groups using a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to select the predictors, multiple logistic regression analysis was used to establish the risk prediction model, and a dynamic nomogram was developed. The Hosmer-Lemeshow (HL) test was performed to determine the model's goodness of fit. The area under the receiver operating characteristic (ROC) curve was used to evaluate the model's prediction efficiency. RESULTS: The risk factors of mental disorders were Sepsis-related organ failure assessment (SOFA) score, Charlson comorbidity index (CCI), delirium duration, ICU depression score and ICU sleep score. The HL test revealed that p = .249, the area under the ROC curve = 0.860, and the corresponding sensitivity and specificity were 84.8% and 71.0%, respectively. The area under the ROC curve of the verification group was 0.848. A mental disorders dynamic nomogram for post-ICU patients was developed based on the regression model. CONCLUSIONS: The prediction model provides a reference for clinically screening patients at high risk of developing post-ICU mental disorders, to enable the implementation of timely preventive management measures. RELEVANCE TO CLINICAL PRACTICE: The dynamic nomogram can be used to systematically monitor various factors associated with mental disorders. Furthermore, nurses need to develop and apply accurate nursing interventions that consider all relevant variables.

8.
Int J Mol Sci ; 24(16)2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37628762

RESUMEN

Phoebe bournei is nationally conserved in China due to its high economic value and positive effect on the ecological environment. P. bournei has an excellent wood structure, making it useful for industrial and domestic applications. Despite its importance, there are only a few studies on the lateral organ boundary domain (LBD) genes in P. bournei. The LBD gene family contributes to prompting rooting in multiple plant species and therefore supports their survival directly. To understand the LBD family in P. bournei, we verified its characteristics in this article. By comparing the sequences of Arabidopsis and identifying conserved domains and motifs, we found that there were 38 members of the LBD family in P. bournei, which were named PbLBD1 to PbLBD38. Through evolutionary analysis, we found that they were divided into two different populations and five subfamilies in total. The LBD gene family in P. bournei (Hemsl.) Yang species had two subfamilies, including 32 genes in Class I and 6 genes in Class II. It mainly consists of a Lateral Organ Boundary (LOB) conservative domain, and the protein structure is mostly "Y"-shaped. The gene expression pattern of the LBD gene family showed that the LBD genes were mainly expressed in lateral organs of plants, such as flowers and fruits. The response of LBD transcription factors to red and blue light was summarized, and several models of optogenetic expression regulation were proposed. The effect of regulatory mechanisms on plant rooting was also predicted. Moreover, quantitative real-time PCR (qRT-PCR) revealed that most PbLBDs were differentially expressed under cold, heat, drought, and salt stresses, indicating that PbLBDs might play different functions depending on the type of abiotic stress. This study provides the foundation for further research on the function of LBD in this tree species in the future.


Asunto(s)
Arabidopsis , Lauraceae , Evolución Biológica , China , Sequías
9.
J Proteome Res ; 22(9): 2909-2924, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37545086

RESUMEN

Protein lysine acetylation is a dynamic post-translational modification (PTM) that regulates a wide spectrum of cellular events including aging. General control nonderepressible 5 (GCN5) is a highly conserved lysine acetyltransferase (KAT). However, the acetylation substrates of GCN5 in vivo remain poorly studied, and moreover, how lysine acetylation changes with age and the contribution of KATs to aging remain to be addressed. Here, using Drosophila, we perform label-free quantitative acetylomic analysis, identifying new substrates of GCN5 in the adult and aging process. We further characterize the dynamics of protein acetylation with age, which exhibits a trend of increase. Since the expression of endogenous fly Gcn5 progressively increases during aging, we reason that, by combining the substrate analysis, the increase in acetylation with age is triggered, at least in part, by GCN5. Collectively, our study substantially expands the atlas of GCN5 substrates in vivo, provides a resource of protein acetylation that naturally occurs with age, and demonstrates how individual KAT contributes to the aging acetylome.


Asunto(s)
Proteínas de Drosophila , Histona Acetiltransferasas , Lisina Acetiltransferasas , Animales , Acetilación , Drosophila , Histona Acetiltransferasas/metabolismo , Lisina/metabolismo , Lisina Acetiltransferasas/metabolismo , Proteínas de Drosophila/metabolismo
10.
Int J Mol Sci ; 24(12)2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37373489

RESUMEN

GATA transcription factors are crucial proteins in regulating transcription and are characterized by a type-IV zinc finger DNA-binding domain. They play a significant role in the growth and development of plants. While the GATA family gene has been identified in several plant species, it has not yet been reported in Phoebe bournei. In this study, 22 GATA family genes were identified from the P. bournei genome, and their physicochemical properties, chromosomal distribution, subcellular localization, phylogenetic tree, conserved motif, gene structure, cis-regulatory elements in promoters, and expression in plant tissues were analyzed. Phylogenetic analysis showed that the PbGATAs were clearly divided into four subfamilies. They are unequally distributed across 11 out of 12 chromosomes, except chromosome 9. Promoter cis-elements are mostly involved in environmental stress and hormonal regulation. Further studies showed that PbGATA11 was localized to chloroplasts and expressed in five tissues, including the root bark, root xylem, stem bark, stem xylem, and leaf, which means that PbGATA11 may have a potential role in the regulation of chlorophyll synthesis. Finally, the expression profiles of four representative genes, PbGATA5, PbGATA12, PbGATA16, and PbGATA22, under drought, salinity, and temperature stress, were detected by qRT-PCR. The results showed that PbGATA5, PbGATA22, and PbGATA16 were significantly expressed under drought stress. PbGATA12 and PbGATA22 were significantly expressed after 8 h of low-temperature stress at 10 °C. This study concludes that the growth and development of the PbGATA family gene in P. bournei in coping with adversity stress are crucial. This study provides new ideas for studying the evolution of GATAs, provides useful information for future functional analysis of PbGATA genes, and helps better understand the abiotic stress response of P. bournei.


Asunto(s)
Factores de Transcripción GATA , Dedos de Zinc , Filogenia , Factores de Transcripción GATA/genética , Factores de Transcripción GATA/metabolismo , Regiones Promotoras Genéticas , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Familia de Multigenes , Genoma de Planta
11.
Phys Med Biol ; 68(14)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37343570

RESUMEN

Objective.3D ultrasound non-rigid registration is significant for intraoperative motion compensation. Nevertheless, distorted textures in the registered image due to the poor image quality and low signal-to-noise ratio of ultrasound images reduce the accuracy and efficiency of the existing methods.Approach.A novel 3D ultrasound non-rigid registration objective function with texture and content constraints in both image space and multiscale feature space based on an unsupervised generative adversarial network based registration framework is proposed to eliminate distorted textures. A similarity metric in the image space is formulated based on combining self-structural constraint with intensity to strengthen the robustness to abnormal intensity change compared with common intensity-based metrics. The proposed framework takes two discriminators as feature extractors to formulate the texture and content similarity between the registered image and the fixed image in the multiscale feature space respectively. A distinctive alternating training strategy is established to jointly optimize the combination of various similarity loss functions to overcome the difficulty and instability of training convergence and balance the training of generator and discriminators.Main results.Compared with five registration methods, the proposed method is evaluated both with small and large deformations, and achieves the best registration accuracy with average target registration error of 1.089 mm and 2.139 mm in cases of small and large deformations, respectively. The performance on peak signal to noise ratio (PSNR) and structural similarity (SSIM) also proves the effective constraints on distorted textures of the proposed method (PSNR is 31.693 dB and SSIM is 0.9 in the case of small deformation; PSNR is 28.177 dB and SSIM is 0.853 in the case of large deformation).Significance.The proposed 3D ultrasound non-rigid registration method based on texture and content constraints with the distinctive alternating training strategy can eliminate the distorted textures with improving the registration accuracy.


Asunto(s)
Imagenología Tridimensional , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Imagenología Tridimensional/métodos , Ultrasonografía , Relación Señal-Ruido , Movimiento (Física) , Procesamiento de Imagen Asistido por Computador/métodos
12.
J Biosaf Biosecur ; 5(1): 32-38, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36936134

RESUMEN

Aerosol transmission is an important disease transmission route and has been especially pertinent to hospital and biosafety laboratories during the SARS-CoV-2 pandemic. The thermal resistance of airborne SARS-CoV-2 is lower than that of Bacillus subtilis spores, which are often used to test the effectiveness of SARS-CoV-2 and other pathogen disinfection methods. Herein, we propose a new method to test the disinfection ability of a flowing air disinfector (a digital electromagnetic induction air heater) using B. subtilis spores. The study provides an alternative air disinfection test method. The new test system combined an aerosol generator and a respiratory filter designed in-house and could effectively recover spores on the filter membrane at the air outlet after passing through the flowing air disinfector. The total number of bacterial spores used in the test was within the range of 5 × 105-5 × 106 colony-forming units (CFUs) specified in the technical standard for disinfection. The calculation was based on the calculation method in Air Disinfection Effect Appraisal Test in Technical Standard for Disinfection (2002 Edition). At an air speed of 3.5 m/s, we used a digital electromagnetic induction air heater to disinfect flowing air containing 4.100 × 106 CFUs of B. subtilis spores and determined that the minimum disinfection temperature was 350 °C for a killing rate of 99.99%. At 400 °C, additional experiments using higher spore concentrations (4.700 × 106 ± 1.871 × 105 CFU) and a higher airspeed (4 m/s) showed that the killing rate remained>99.99%. B. subtilis spores, as a biological indicator for testing the efficiency of dry-heat sterilization, were killed by the high temperatures used in this system. The proposed method used to test the flowing air disinfector is simple, stable, and effective. This study provides a reference for the development of test systems that can assess the disinfection ability of flowing air disinfectors.

13.
Mol Cell Proteomics ; 21(9): 100276, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35931320

RESUMEN

Lysine acetylation is a reversible and dynamic post-translational modification that plays vital roles in regulating multiple cellular processes including aging. However, acetylome-wide analysis in the aging process remains poorly studied in mammalian tissues. Nicotinamide adenine dinucleotide (NAD+), a hub metabolite, benefits health span at least in part due to the activation of Sirtuins, a family of NAD+-consuming deacetylases, indicating changes in acetylome. Here, we combine two antibodies for the enrichment of acetylated peptides and perform label-free quantitative acetylomic analysis of mouse livers during natural aging and upon the treatment of beta-nicotinamide mononucleotide (NMN), a NAD+ booster. Our study describes previously unknown acetylation sites and reveals the acetylome-wide dynamics with age as well as upon the treatment of NMN. We discover protein acetylation events as potential aging biomarkers. We demonstrate that the life-beneficial effect of NMN could be partially reflected by the changes in age-related protein acetylation. Our quantitative assessment indicates that NMN has mild effects on acetylation sites previously reported as substrates of Sirtuins. Collectively, our data analyze protein acetylation with age, laying critical foundation for the functional study of protein post-translational modification essential for healthy aging and perhaps disease conditions.


Asunto(s)
Mononucleótido de Nicotinamida , Sirtuinas , Acetilación , Animales , Hígado/metabolismo , Lisina/metabolismo , Mamíferos/metabolismo , Ratones , NAD/metabolismo , Mononucleótido de Nicotinamida/metabolismo , Mononucleótido de Nicotinamida/farmacología , Sirtuinas/metabolismo
14.
Biochim Biophys Acta Mol Basis Dis ; 1868(10): 166472, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35752384

RESUMEN

During the epidemic, the individuals with underlying diseases usually have a higher rate of mortality. Diabetes is highly prevalent worldwide, making it a frequent comorbidity in dengue fever patients. Therefore, understanding the relationship between dengue virus (DENV) infection and diabetes is important. We first demonstrated that DENV-3 infection down-regulated the expression of IRS-1. In vitro, treatment of HepG2 cells with TNF-α inhibitors and siRNA proved that after DENV-3 infection in HepG2 cells, cellular TNF-α secretion was increased, which negatively regulated IRS-1, thereby leading to an insulin-resistant state. In vivo, DENV-3 induced insulin resistance (IR) in hepatocytes by promoting the secretion of TNF-α and inhibiting the expression of IRS-1 was proved. In vivo approaches also showed that after DENV-3 infection, TNF-α levels in the serum of C57BL/6 mice with insulin resistance increased, and upon TNF-α antagonist III treatment, IRS-1 expression in the liver, reduced by infection, was upregulated. In addition, transcriptomic analysis revealed more negative regulatory events in the insulin receptor signaling pathway after DENV-3 infection. This is the first report of a link between DENV-3 infection and insulin resistance, and it lays a foundation for further research.


Asunto(s)
Virus del Dengue , Proteínas Sustrato del Receptor de Insulina/metabolismo , Resistencia a la Insulina , Animales , Virus del Dengue/metabolismo , Regulación hacia Abajo , Resistencia a la Insulina/genética , Ratones , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
15.
Nat Commun ; 13(1): 3518, 2022 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-35725845

RESUMEN

System-wide metabolic homeostasis is crucial for maintaining physiological functions of living organisms. Stable-isotope tracing metabolomics allows to unravel metabolic activity quantitatively by measuring the isotopically labeled metabolites, but has been largely restricted by coverage. Delineating system-wide metabolic homeostasis at the whole-organism level remains challenging. Here, we develop a global isotope tracing metabolomics technology to measure labeled metabolites with a metabolome-wide coverage. Using Drosophila as an aging model organism, we probe the in vivo tracing kinetics with quantitative information on labeling patterns, extents and rates on a metabolome-wide scale. We curate a system-wide metabolic network to characterize metabolic homeostasis and disclose a system-wide loss of metabolic coordinations that impacts both intra- and inter-tissue metabolic homeostasis significantly during Drosophila aging. Importantly, we reveal an unappreciated metabolic diversion from glycolysis to serine metabolism and purine metabolism as Drosophila aging. The developed technology facilitates a system-level understanding of metabolic regulation in living organisms.


Asunto(s)
Drosophila , Metabolómica , Envejecimiento , Animales , Isótopos de Carbono , Marcaje Isotópico , Metaboloma
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1275-1279, 2021 Aug.
Artículo en Chino | MEDLINE | ID: mdl-34362516

RESUMEN

OBJECTIVE: To explore the application value of next generation sequencing (NGS) in preimplantation genetic diagnosis of α/ß complex thalassemia couple. METHODS: The coding regions of α-globin genes (HBA1, HBA2) and ß-globin gene (HBB) were selected as the target regions. The high-density and closely linked single nucleotide polymorphism (SNP) sites were selected as the genetic linkage markers in the upstream and downstream 2M regions of the gene. After NGS, the effective SNP sites were selected to construct the haplotype of the couple, and the risk chromosome of the mutation carried by the couple was determined. The NGS technology was used to sequence the variations of HBA1, HBA2 and HBB directly and construct haplotype linkage analysis for preimplantation genetic diagnosis. RESULTS: Direct sequencing and haplotype linkage analysis of HBA1, HBA2 and HBB showed that two of the six blastocysts were α/ß complex thalassemia, one was ß-thalassemia heterozygote, two were α-thalassemias heterozygotes, and one was intermediate α-thalassemia. A well-developed embryo underwent preimplantation genetic diagnosis was implanted into the mother's uterus, and a healthy infant was born at term. CONCLUSION: Preimplantation genetic diagnosis can be carried out by NGS technology in α/ß complex thalassemia couples, and abortion caused by aneuploid embryo selection can be avoided.


Asunto(s)
Diagnóstico Preimplantación , Talasemia alfa , Talasemia beta , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Embarazo , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genética
17.
Sci Total Environ ; 755(Pt 1): 142456, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33017760

RESUMEN

Field measurements were conducted near Qingdao Port to characterize the particulate air pollutants, assess the spatial and seasonal characteristics of the pollutants, and identify the contribution from ship traffic emissions. By utilizing multiple statistical methods and data collected at two sites in Qingdao, we comprehensively explored the PM2.5 seasonal characteristics and source apportionments of different PM2.5 constituents, especially those originating from ship emissions, and identified potential source regions for samples collected in Qingdao. In this study, 118 concurrent daily PM2.5 samples were collected from August 2018 to May 2019 at a port site (QH) and a coastal background site (BG). Vanadium (V) and Nickel (Ni) are the dominant metal elements from crude oil and crude oil combustion emissions. The significant correlations between V and Ni at both sampling sites, indicating that shipping emissions have a significant impact on the port and background area. Additionally, Ni and other metals showed significant correlations at the BG site, implying Ni also emission from the land-based oil at this site. The positive matrix factorization (PMF) model identified six main sources for the PM2.5 samples in Qingdao, and they are coal combustion, industrial emissions/mineral dust, marine vessel emissions, secondary aerosols/biomass burning, sea salt/crustal emissions, and vehicle exhaust, respectively. Marine vessel emissions were the dominant contributor to PM2.5 in Qingdao during the sampling periods (25.05%). The potential source contribution function (PSCF) analysis suggested that the Yellow Sea and Jiaodong Peninsula were the major sources regions for PM2.5 in Qingdao. The Yellow Sea and Bohai Sea were the potential source regions for shipping emissions in Qingdao. Therefore, efforts to control shipping emissions should be strengthened not only at the Qingdao Port but also in surrounding ports.

18.
Sci Total Environ ; 720: 137521, 2020 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-32145622

RESUMEN

Daytime and nighttime PM2.5 samples were collected at a road tunnel located in Qingdao, China. The mass concentrations and chemical compositions of polycyclic aromatic hydrocarbons (PAHs), nitrated PAHs (NPAHs) and oxygenated-PAHs (OPAHs) were analysed to determine the variation characteristics and sources. The concentrations in exit were obviously higher than those of entrance in the tunnel. Fluoranthene (FLT) and Pyrene (PYR) were the most abundant PAHs, 2 + 3-nitrofluoranthene (2 + 3N-FLA), 1-nitropyrene (1N-PYR) and 2-nitropyrene (2N-PYR) were the dominant NPAHs, and 9-fluorenone (9-FO) and 9,10-anthraquinone (9,10-ANQ) were the most abundant OPAHs. The high rings (4-6 rings) PAHs accounted for over 90% of the total PM2.5-bound PAH concentrations, most of which were considered as motor vehicle emissions. Based on the diagnostics ratios and PCA results, the most important sources of PAHs and NPAHs were estimated as gasoline and diesel vehicles emissions in the tunnel. In addition, non-exhausts (such as road dust, brake line, asphalt and tires wear) also had some contributions to PAHs and NPAHs. The average emission factors were 60.98, 9.02 and 8.47 µg veh-1 km-1 for total PM2.5-bound PAHs, NPAHs and OPAHs, respectively. The emission factors of high rings (4-6 rings) PAHs were greater than those with low rings (2-3 rings). 1N-PYR had the highest emission factor in all measured NPAHs, while the emission factors for the two highest OPAHs were 9-FO and 9,10-ANQ in this tunnel.

19.
Front Pharmacol ; 11: 604404, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33384603

RESUMEN

Nicotinamide mononucleotide (NMN), a key precursory metabolite of NAD+, has been shown to elevate the cellular level of NAD+ and ameliorate various age-related diseases. Despite these progresses, systemic evaluation pertaining to the subacute toxicity of NMN remains to be determined. Here, we examine the subacute toxicity of NMN in mice and beagle dogs. Mice were gavaged with a saturated concentration of NMN solution at the maximum intragastric dose once or twice per day for 7 days. Dogs were gavaged twice per day for 14 days. In mice, NMN administrated once per day for 7 days is well tolerated with minimal deleterious effects. Upon higher dosage, we observe slightly increased level of alamine aminotransferase, while other biomarkers remain unchanged. Consistently, administration of NMN in beagle dogs only results in mild increases in creatinine and uric acid. Together, our study highlights the safety of NMN, providing a possible safe dose range for oral administration of NMN.

20.
Biomed Res Int ; 2019: 5382130, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31275975

RESUMEN

OBJECTIVE: Dyslipidemia is one of the most important modifiable risk factors for cardiovascular disease. Diet and lifestyle interventions positively contribute to the management of dyslipidemia. Adequate knowledge of the correct diet for dyslipidemia is an effective preventive strategy against cardiovascular disease. METHOD: This study developed a questionnaire to test dyslipidemia dietary knowledge. The initial, multiple-choice dyslipidemia dietary knowledge questionnaire (DDKQ) was formed based on a literature review of previous studies. Two Delphi rounds were performed to ensure content validity and face validity, items were pretested and filtered through item analysis, and the reliability and validity of the final questionnaire were checked. RESULTS: The DDKQ consisted of 5 parts, with 25 items in total. It demonstrated adequate content validity (0.94), face validity, internal consistency (KR20 = 0.67), and test-retest reliability (0.74). The mean item difficulty (P) was 0.55 and ranged from 0.15 to 0.83, and the mean item discrimination index (D) was 0.36, ranging from 0.21 to 0.58. The questionnaire was also able to distinguish between participants with/without a medical background; medical workers produced significantly higher total scores (16.70±2.84 vs. 14.57±4.26, p< 0.05). CONCLUSION: The DDKQ is a reliable and valid measure of dyslipidemia dietary knowledge. It is suitable for providing scientific assessments for targeted health education interventions.


Asunto(s)
Dieta , Dislipidemias/epidemiología , Conocimiento , Encuestas y Cuestionarios , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA