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  • Frontiers Media SA  (9)
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  • Frontiers Media SA  (9)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-8-12)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-8-12)
    Abstract: Endoplasmic reticulum (ER) is the principal organelle for protein synthesis, such as hepatokines and transmembrane proteins, and is critical for maintaining physiological function. Dysfunction of ER is associated with metabolic disorders. However, the role of ER homeostasis as well as hepatokines in the progression of non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Here we comprehensively analyzed the RNA-seq profiles of liver biopsies from 206 NAFLD patients and 10 controls from dataset GSE135251. The co-expression modules were constructed based on weighted gene co-expression network analysis and six co-expression modules were identified, of which brown module stood out to be significantly associated with fibrosis stage and NAFLD activity score (NAS). Subsequently, cytoscape with cytoHubba plugin was applied to identify hub genes in the brown module. GO and KEGG enrichment analysis of the top 20 hub genes were performed and showed the involvement of extracellular matrix formation, collagen synthesis and decomposition, etc. Further, the expression of the top 20 hub genes were found to be a consistent increasing trend as the fibrosis stages and NAS increased, which have been validated both in HFD fed and HFHC fed mice. Among these genes, THY1 , PTGDS , TMPRSS3 , SPON1 , COL1A2 , RHBDF1 , COL3A1 , COL5A1 , COL1A1 and IGFBP7 performed well in distinguishing fibrosis stage, while COL1A2 , COL3A1 , THY1 , RHBDF1 and COL1A2 exhibited good capacity to discriminate NAS. Besides, RHBDF1 , COL3A1 , QSOX1 , STING1 , COL5A1 , IGFBP7 , COL4A2 , COL1A1 , FKBP10 and COL1A2 also showed a strong power in the diagnosis of NAFLD. In addition, COL1A1 , COL1A2 , COL3A1 , COL8A2 , IGFBP7 , PGF , PTGDS , SPON1 , THY1 and TIMP1 were identified as secretome genes from the top 20 hub genes. Of them, circulated THY1 and collagen III level were validated to be significantly elevated in the MCD diet-induced mice. Thus, we provided a systemic view on understanding the pathological roles and mechanisms of ER as well as secretome in NAFLD progression. THY1 , COL1A1 , COL1A2 , COL3A1 and RHBDF1 could be served as candidate biomarkers to evaluate the progression of NAFLD.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 2
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-5-24)
    Abstract: Contrast-enhanced high-resolution magnetic resonance imaging (CE-HR-MRI) is a useful imaging modality to assess vulnerable plaques in intracranial atherosclerotic stenosis (ICAS) patients. We studied the relationship between the fibrinogen-to-albumin ratio (FAR) and plaque enhancement in patients with ICAS. Methods We retrospectively enrolled consecutive ICAS patients who had undergone CE-HR-MRI. The degree of plaque enhancement on CE-HR-MRI was evaluated both qualitatively and quantitatively. Enrolled patients were classified into no enhancement, mild enhancement, and obvious enhancement groups. An independent association of the FAR with plaque enhancement was identified by multivariate logistic regression and receiver operating characteristic (ROC) curve analyses. Results Of the 69 enrolled patients, 40 (58%) were classified into the no/mild enhancement group, and 29 (42%) into the obvious enhancement group. The obvious enhancement group had a significantly higher FAR than the no/mild enhancement group (7.36 vs. 6.05, p  = 0.001). After adjusting for potential confounders, the FAR was still significantly independently associated with obvious plaque enhancement in multiple regression analysis (odds ratio: 1.399, 95% confidence interval [CI]: 1.080–1.813; p  = 0.011). ROC curve analysis revealed that FAR & gt;6.37 predicted obvious plaque enhancement with 75.86% sensitivity and 67.50% specificity (area under the ROC curve = 0.726, 95% CI: 0.606–0.827, p   & lt; 0.001). Conclusion The FAR can serve as an independent predictor of the degree of plaque enhancement on CE-HR-MRI in patients with ICAS. Also, as an inflammatory marker, the FAR has potential as a serological biomarker of intracranial atherosclerotic plaque vulnerability.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-12-5)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-12-5)
    Abstract: Many studies have shown that ingestion of the T-2 toxin is harmful to articular cartilage. However, the mechanisms underlying damaged articular cartilage induced by T-2 toxin have not been elucidated. Twenty-four SD rats were randomly divided into T-2 toxin and control groups. In the control group, the 12 rats were administered 4% absolute ethanol by gavage, and in the T-2 toxin group, the 12 rats were administered T-2 toxin (100 ng/g, BW/day) by gavage. After the rats were sacrificed, the knee joints were collected, and RNA was extracted using TRIzol reagent for RNA sequencing (RNA-seq). Differentially expressed mRNA was identified based on p & lt; 0.05 and | log 2 (fold change) | & gt; 1. The T-2 toxin-related genes were obtained from the GeneCards database. An online tool ( https://www.bioinformatics.com.cn ) was used for enrichment analysis. Hematoxylin and eosin (H & amp;E) staining was used to observe damaged articular cartilage, and immunohistochemical (IHC) staining was used to validate differentially expressed proteins. The H & amp;E staining shows the number of cells decreased significantly, and the arrangement of chondrocytes became disordered in the T-2 toxin group. RNA-seq analysis identified 195 upregulated and 89 downregulated mRNAs in the T-2 toxin group. The top immune-related biological processes (Gene Ontology) were regulation of hormone secretion, regulation of peptide hormone secretion, and regulation of transcription involved in cell fate commitment. KEGG pathway enrichment analysis revealed that the IL-17 and tumor necrosis factor signaling pathways were significantly expressed, and the IL-17 signaling pathway was also identified in the enrichment analysis of T-2 toxin-related genes. Also, Mmp3, Tnf, Mapk10, Ccl11, Creb5, Cxcl2, and Cebpb were significantly enriched in the two pathways. The immunohistochemical staining showed that the levels of Mmp3 and Tnf proteins were significantly increased in the T-2 toxin group, which was consistent with the RNA-seq results. This study revealed the critical roles of IL-17 and TNF signaling pathways in damaged cartilage induced by T-2 toxin.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Genetics Vol. 13 ( 2023-1-4)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2023-1-4)
    Abstract: Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C & gt;T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677 C & gt;T), is linked to an increased risk of IS in different age groups and ancestry groups. Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations. Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C & gt;T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33–1.61; p & lt; 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36–1.71; p & lt; 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24–1.48; p & lt; 0.001), homozygous model (OR = 1.82; 95%CI = 1.58–2.11; p & lt; 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27–1.48; p & lt; 0.001)]. Further subgroup analyses indicated that the MTHFR r s1801133 (677C & gt;T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations ( p & lt; 0.001). Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C & gt;T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606823-0
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  • 5
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-2-10)
    Abstract: The use of differentiating human induced pluripotent stem cells (hiPSCs) in mini-tissue organoids provides an invaluable resource for regenerative medicine applications, particularly in the field of disease modeling. However, most studies using a kidney organoid model, focused solely on the transcriptomics and did not explore mechanisms of regulating kidney organoids related to metabolic effects and maturational phenotype. Here, we applied metabolomics coupled with transcriptomics to investigate the metabolic dynamics and function during kidney organoid differentiation. Not only did we validate the dominant metabolic alteration from glycolysis to oxidative phosphorylation in the iPSC differentiation process but we also showed that glycine, serine, and threonine metabolism had a regulatory role during kidney organoid formation and lineage maturation. Notably, serine had a role in regulating S-adenosylmethionine (SAM) to facilitate kidney organoid formation by altering DNA methylation. Our data revealed that analysis of metabolic characterization broadens our ability to understand phenotype regulation. The utilization of this comparative omics approach, in studying kidney organoid formation, can aid in deciphering unique knowledge about the biological and physiological processes involved in organoid-based disease modeling or drug screening.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606823-0
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Materials Vol. 9 ( 2022-10-13)
    In: Frontiers in Materials, Frontiers Media SA, Vol. 9 ( 2022-10-13)
    Abstract: Using ultra-high performance concrete (UHPC) as the pavement layer on the orthotropic steel deck (OSD) can greatly enhance the rigidity to solve the fatigue cracking of the steel deck and the resulting damage to the pavement layer. However, the thin UHPC layer limits the extensive use of the short stud connector. In this study, three types of interfaces were designed by introducing different additives into the epoxy matrix, and the shear properties of each interface and short stud connector were compared. Then, the influence of short stud connectors and optimized interface on the composite bridge deck’s bending property was analyzed through the composite bridge deck’s bending test. Moreover, the mechanical behavior of the interface in the composite bridge deck is discussed based on the finite element model. The results show that the ultimate load of the composite bridge deck with the optimized interface is reduced by 21.5% compared with that of the composite bridge deck with the short stud connector. However, the composite bridge deck with the optimized interface has higher bending stiffness before failure and is less affected by cyclic loading. Moreover, the composite bridge deck with the optimized interface is unsuitable for cyclic loading conditions when the defect area reaches 30%. Finally, the numerical simulation of the composite bridge deck with the optimized interface is successfully realized based on the cohesive zone model, and the applicability of the interface in the composite bridge deck is verified.
    Type of Medium: Online Resource
    ISSN: 2296-8016
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2759394-0
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  • 7
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 12 ( 2021-8-4)
    Abstract: microRNA (miRNA) plays important roles in regulating various biological processes, including host-pathogen interaction. Recent studies have demonstrated that virus-encoded miRNAs can manipulate host gene expression to ensure viral effective multiplication. Bombyx mori cypovirus (BmCPV), a double-stranded RNA virus with a segmented genome, is one of the important pathogens for the economically important insect silkworm. Our present study indicated that two putative miRNAs encoded by BmCPV could promote viral replication by inhibiting the gene expression of B. mori GTP-binding nuclear protein Ran ( BmRan ), an essential component of the exportin-5-mediated nucleocytoplasmic transport of small RNAs. BmCPV-miR-1 and BmCPV-miR-3 are two of the BmCPV-encoded miRNAs identified in our previous studies. BmRan is a common target gene of them with binding sites all located in the 3′-untranslated region (3′-UTR) of its mRNA. The expression levels of the two miRNAs in the midgut of larvae infected with BmCPV gradually increased with the advance of infection, while the expression of the target gene BmRan decreased gradually. The miRNAs and the recombinant target gene consisting of reporter gene mCherry and 3′-UTR of BmRan mRNA were expressed in HEK293T cells for validating the interaction between the miRNAs and the target gene. qRT-PCR results revealed that BmCPV-miR-1 and BmCPV-miR-3 negatively regulate target gene expression not only separately but also cooperatively by binding to the 3′-UTR of BmRan mRNA. By transfecting miRNA mimics into BmN cells and injecting the mimics into the body of silkworm larvae, it was indicated that both BmCPV-miR-1 and BmCPV-miR-3 could repress the expression of BmRan in BmN cells and in the silkworm, and the cooperative action of the two miRNAs could enhance the repression of BmRan expression. Furthermore, the repression of BmRan could facilitate the replication of BmCPV genomic RNAs. It is speculated that BmCPV-miR-1 and BmCPV-miR-3 might reduce the generation of host miRNAs by inhibiting expression of BmRan , thus creating a favorable intracellular environment for virus replication. Our results are helpful to better understand the pathogenic mechanism of BmCPV to the silkworm, and provide insights into one of the evasion strategies used by viruses to counter the host defense for their effective multiplication.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564217-0
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  • 8
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 9 ( 2021-8-26)
    Abstract: Introduction: Hirschsprung's disease is a common digestive tract malformation in children, and the Soave procedure is one of the classic surgical methods for Hirschsprung's disease (HD). Fecal incontinence is one of the most common postoperative complications that can cause significant distress to the patients and their family, the incidence of which is 20% in a recent series. Biofeedback therapy (BFT) can be an effective treatment for managing anorectal disorders, but there has been little report of the efficacy of BFT for the treatment of fecal incontinence after the Soave procedure, and the main objective of this study is to evaluate it. Methods: We retrospectively analyzed postoperative fecal incontinence in 46 children who received the Soave procedure for HD and who received BFT at our institution from March 2016 to February 2020, which included 38 males and 8 females (mean age 8.1 years, from 3.7 to 14 years). Anal sphincter contraction training was performed using BFT for 10 days per session in the hospital, one time each day, and 20 min each time. BFT was performed by employing visual and verbal feedback techniques using the biofeedback instrument. Long-term functional outcomes were objectively assessed using the Rintala Bowel Function Score (RBFS), and the patients were scored according to the sum total as excellent (18–20 points, 0 case), good (11–16 points, 0 case), fair (9–11 points, 9 cases), or poor (6–9 points, 37 cases). Defecation questionnaires and anorectal manometry were completed pretreatment and after three, six, or nine sessions, and primary outcome measures of anorectal manometry were anal maximal contraction pressure (AMCP), anal longest contraction time (ALCT), rectal rest pressure (RRP), and anal rest pressure (ARP). Results: Followed up from 6 months to 4 years, the symptoms of fecal incontinence disappeared completely in 39 (84.78%) patients. Among them, 14 (30.43%) had complete disappearance of symptoms after 3 sessions of treatment, 25 (54.34%) patients had improved symptoms after 6 sessions of treatment, symptoms completely disappeared after 6 sessions of treatment, and 7 (15.22%) cases still suffered fecal incontinence mildly. The AMCP after three and six sessions in the poor group was significantly increased compared with that before treatment [(85.87 ± 31.75) mmHg vs. (135.33 ± 37.69) mmHg vs. (128.41 ± 33.45) mmHg, P & lt; 0.05]. The ALCT and ARP showed the same trend, while the RRP after three and six sessions were not significant ( P & gt; 0.05). The mean (±SD) score of the RBFS increased from 9 to 17.40 ± 0.84 in the fair group, while it increased from 7.22 ± 0.76 to 16.58 ± 1.66 in the poor group after six sessions ( P & lt; 0.05). Conclusion: Biofeedback therapy is a safe and effective treatment of fecal incontinence after the Soave procedure of children for Hirschsprung's disease. It is beneficial to design the individualized treatment programs for the children with varying degrees of fecal incontinence.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2711999-3
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2024
    In:  Frontiers in Materials Vol. 11 ( 2024-3-19)
    In: Frontiers in Materials, Frontiers Media SA, Vol. 11 ( 2024-3-19)
    Abstract: Conventional stud connectors were proved to be inconvenient for the later disassembly and replacement in ultra-high performance concrete (UHPC) bridge decks. In this study, the headless studs which is a type of studs with their heads removed were employed as a substitute for conventional stud connectors, aiming to enhance the detachability of the bridge decks on the premise of ensuring the anti-lift bearing capacity of the decks. Three push-out specimens containing the headless studs with a diameter of 13 mm were carried out to study the mechanical properties of headless studs. In addition, the finite element model was developed to reveal the failure mechanism of headless studs in UHPC. Results indicated that the load-slip curve of headless stud connector can be divided into elastic stage, plastic stage and failure stage. The failure mode of headless studs was the shear fracture at the root of stud shank. Headless stud connections under cyclic loading can produce greater plastic deformation. The ultimate shear capacity and shear stiffness of headless studs were lower than those of conventional studs. Additionally, the UHPC slabs configured with headless studs have a small quantity of separation at the steel-UHPC interface, so it is suggested to use headless studs and conventional studs together in UHPC slabs to ensure the necessary anti-lift bearing capacity. Finite element analysis indicated that in the elastic stage, the bearing capacity of the push-specimen was dominated by the material properties of the headless stud. After entering the plastic stage, the bearing capacity of the push-specimen was mainly controlled by the UHPC below the headless stud.
    Type of Medium: Online Resource
    ISSN: 2296-8016
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2759394-0
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