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  • Frontiers Media SA  (34)
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  • Frontiers Media SA  (34)
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  • 1
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-2-2)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-2-2)
    Kurzfassung: The role of the tumor microenvironment (TME) in the progression of colorectal cancer (CRC) and its acquisition of resistance to treatment become the research hotspots. As an important component of TME, the tumor-associated macrophages (TAMs) regulate multiple critical oncogenic processes, namely, occurrence, proliferation, metastasis, and drug resistance in CRC. In this review, we have discussed the functional and therapeutic significance of TAMs in CRC. M1 macrophages act as the tumor suppressor while M2 macrophages promote CRC. The polarization of TAMs is mainly regulated by the pathways such as NFKB1 pathways, STAT3 pathways, WNT5A pathways, and PI3K pathways in CRC. Furthermore, the M2 polarization of TAMs is not only controllable but also reversible. Finally, we provide insights into the TAMs-targeted therapeutic strategies.
    Materialart: Online-Ressource
    ISSN: 2234-943X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2649216-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2023
    In:  Frontiers in Public Health Vol. 11 ( 2023-8-23)
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 11 ( 2023-8-23)
    Kurzfassung: Co-existence of colistin, β-lactam and carbapenem in multidrug-resistant Enterobacteriaceae isolates poses a serious threat to public health. In this study, we investigated and characterized the co-occurrence of bla CTX-M-65 , bla OXA-1 , and mcr-1.1 strain isolated from a clinical extensively-drug-resistant Escherichia coli ST744 in Shanghai. Methods Antimicrobial susceptibility test was carried out by agar dilution methods. Whole genome sequencing was conducted, and resistance genes, and sequence types of colistin in E. coli isolates were analyzed. Plasmid stability and amino acid mutations were assessed in E. coli isolates. Results A colistin resistant E. coli ST744, named ECPX221, was identified out of 145 fecal samples collected. The strain carries a 60,168 IncI2 plasmid with the mcr-1.1 gene. The strain also has bla CTX-M-65 , bla OXA-1 , dfrA 14, qnrS1 , cmlA5 , arr2 , ampC , aph(4)-Ia , sul1 , and aadA5 resistance genes. The plasmid pECPX221 was capable of conjugation with an efficiency of 2.6 × 10 −2 . Notably, 45% of the transconjugants were determined as mcr-1.1 -harboring in the colistin-free environment after 60 generation of passage. No mutations occurred in pmrB , mgrB , and phoPQ gene in the mcr-1.1 -harboring transconjugants. Bioinformatic analysis indicated pECPX221 shared highly similar backbone with the previously reported mcr-1.1 -harboring pAH62-1, pMFDS1339.1, pSCZE4, and p2018-10-2CC. Furthermore, sequencing and phylogenetic analyses revealed a similarity between other MCR-1-homolog proteins, indicating that ECPX221 was colistin resistant. Conclusion The stable transferable mcr-1.1 -harboring plasmid found in the E. coli ST744 strain indicated the high risk to disseminate the extensively-drug-resistance phenotype among Enterobacteriaceae .
    Materialart: Online-Ressource
    ISSN: 2296-2565
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2711781-9
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-11-3)
    Kurzfassung: The nucleus accumbens (NAc) is involved in the expression of cocaine addictive phenotypes, including acquisition, extinction, and reinstatement. In the NAc, D1-medium spiny neurons (MSNs) encode cocaine reward, whereas D2-MSNs encode aversive responses in drug addiction. Glutamate receptor-interacting protein 1 (GRIP1) is known to be associated with cocaine addiction, but the role of GRIP1 in D1-MSNs and D2-MSNs of the NAc in cocaine acquisition and reinstatement remains unknown. Methods A conditioned place preference apparatus was used to establish cocaine acquisition, extinction, and reinstatement in mouse models. GRIP1 expression was evaluated using Western blotting. Furthermore, GRIP1-siRNA and GRIP1 overexpression lentivirus were used to interfere with GRIP1 in the NAc. After the behavioral test, green fluorescent protein immunostaining of brain slices was used to detect spine density. Results GRIP1 expression decreased during cocaine acquisition and reinstatement. GRIP1-siRNA enhanced cocaine-induced CPP behavior in acquisition and reinstatement and regulated associated spine plasticity. Importantly, the decreased GRIP1 expression that mediated cocaine acquisition and reinstatement was mainly driven by the interference of the GRIP1-GluA2 interaction in D1-MSNs and could be blocked by the interference of the GRIP1-GluA2 interaction in D2-MSNs. Interference with the GRIP1-GluA2 interaction in D1- and D2-MSNs decreased spine density in D1- and D2-MSNs, respectively. Conclusion GRIP1 in D1- and D2-MSNs of the NAc differentially modulates cocaine acquisition and reinstatement. GRIP1 downregulation in D1-MSNs has a positive effect on cocaine acquisition and reinstatement, while GRIP1 downregulation in D2-MSNs has a negative effect. Additionally, GRIP1 downregulation in D1-MSNs plays a leading role in cocaine acquisition and reinstatement.
    Materialart: Online-Ressource
    ISSN: 1662-5102
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2452963-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-2-8)
    Kurzfassung: Globally, methamphetamine (MA) is the second most abused drug, with psychotic symptoms being one of the most common adverse effects. Emotional disorders induced by MA abuse have been widely reported both in human and animal models; however, the mechanisms underlying such disorders have not yet been fully elucidated. In this study, a chronic MA administration mouse model was utilized to elucidate the serotonergic pathway involved in MA-induced emotional disorders. After 4 weeks of MA administration, the animals exhibited significantly increased depressive and anxious symptoms. Molecular and morphological evidence showed that chronic MA administration reduced the expression of the 5-hydroxytryptamine (5-HT) rate-limiting enzyme, tryptophan hydroxylase 2, in the dorsal raphe and the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid in the basolateral amygdala (BLA) nuclei. Alterations in both 5-HT and 5-HT receptor levels occurred simultaneously in BLA; quantitative polymerase chain reaction, western blotting, and fluorescence analysis revealed that the expression of the 5-HT2C receptor (5-HT 2C R) increased. Neuropharmacology and virus-mediated silencing strategies confirmed that targeting 5-HT 2C R reversed the depressive and anxious behaviors induced by chronic MA administration. In the BLA, 5-HT 2C R-positive cells co-localized with GABAergic interneurons. The inactivation of 5-HT 2C R ameliorated impaired GABAergic inhibition and decreased BLA activation. Thus, herein, for the first time, we report that the abnormal regulation of 5-HT 2C R is involved in the manifestation of emotional disorder-like symptoms induced by chronic MA use. Our study suggests that 5-HT 2C R in the BLA is a promising clinical target for the treatment of MA-induced emotional disorders.
    Materialart: Online-Ressource
    ISSN: 1663-9812
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2587355-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2021
    In:  Frontiers in Microbiology Vol. 12 ( 2021-12-15)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 12 ( 2021-12-15)
    Kurzfassung: Trichoderma longibrachiatum MD33, a sesquiterpene alkaloid-producing endophyte isolated from Dendrobium nobile , shows potential medical and industrial applications. To understand the molecular mechanisms of sesquiterpene alkaloids production, a comparative transcriptome analysis was performed on strain MD33 and its positive mutant UN32, which was created using Ultraviolet (UV) mutagenesis and nitrogen ion (N + ) implantation. The alkaloid production of UN32 was 2.62 times more than that of MD33. One thousand twenty-four differentially expressed genes (DEGs), including 519 up-regulated and 505 down-regulated genes, were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 139 GO terms and 87 biosynthesis pathways. Dendrobine, arguably the main sesquiterpene alkaloid the strain MD33 produced, might start synthesis through the mevalonate (MVA) pathway. Several MVA pathway enzyme-coding genes (hydroxy-methylglutaryl-CoA synthase, mevalonate kinase, and farnesyl diphosphate synthase) were found to be differentially expressed, suggesting that physical mutagenesis can disrupt genome integrity and gene expression. Some backbone post-modification enzymes and transcript factors were either discovered, suggesting the sesquiterpene alkaloid metabolism in T. longibrachiatum is a complex genetic network. Our findings help to shed light on the underlying molecular regulatory mechanism of sesquiterpene alkaloids production in T. longibrachiatum .
    Materialart: Online-Ressource
    ISSN: 1664-302X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2587354-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2023
    In:  Frontiers in Neurology Vol. 14 ( 2023-9-13)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-9-13)
    Kurzfassung: Stress-related gastrointestinal bleeding (SRGB) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH), and it can present challenges in patient care and treatment. The aim of this study was to explore the clinical significance of the caudate Hounsfield unit (HU) value in the Alberta Stroke Program Early CT (ASPECT) score for predicting SRGB in patients with aSAH. Methods We retrospectively analyzed the data of 531 aSAH patients admitted to our institution between 2019 and 2022. Potential predictors of SRGB were identified using multivariate Cox regression analysis. We used a restricted cubic spline (RCS) to evaluate whether there is a nonlinear relationship between the right caudate HU value and SRGB. MaxStat analysis (titled as maximally selected rank statistics) was performed to identify the optimal cutoff point for the right caudate HU value. Another Kaplan–Meier method with the log-rank test was used to analyze the right caudate HU value in predicting the occurrence of SRGB. Results The incidence rate of SRGB was 17.9%. In the multivariate Cox regression analysis, the right caudate HU value was an independent predictor of SRGB [Hazard ratio (HR) = 0.913; 95% confidence interval (CI): 0.847–0.983, and p  = 0.016]. The RCS indicated that the incidence of developing SRGB reduces with increasing right caudate HU values (nonlinear p  = 0.78). The optimal cut-off value of the right caudate HU was 25.1. Conclusion Among aSAH patients, lower right caudate HU values indicated a higher risk of developing SRGB. Our findings provide further evidence for the relationship between the gastrointestinal system and the brain.
    Materialart: Online-Ressource
    ISSN: 1664-2295
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2564214-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-6-9)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-6-9)
    Kurzfassung: Objective: m 7 G is a post-transcriptional modification modality, however, limited research has been conducted on its role in colon cancer. DNA damage repair (DDR) is an important factor that contributes to colon cancer development, growth and chemoresistance. This study aimed to explore whether m 7 G-related DNA damage repair genes may be used as biomarkers to predict the prognosis of colon cancer patients. Methods: We use non-negative matrix factorization (NMF) to type CRC patients into. Risk models were constructed using different expression genes in two clusters. We assessed the reliability of risk models with DCA curves, and a Nomogram. Meanwhile, The receiver operating characteristic and C-index curves were used to compare the predictive significance of the constructed risk models with other studies. In additional, we examined the significance of risk models on patients’ immunity microenvironment and response to immune therapy. Finally, we used a series of cellular experiments to validate the effect of model genes on the malignant progression of CRC cells. Results: Twenty-eight m 7 G genes were obtained from the GSEA database. Multivariate Cox and LASSO Cox regression analysis was performed and eleven m 7 G-related DDR genes were identified for constructing the risk model. Survival and stage of CRC patients were worser in the high-risk group than in the low-risk group for both the training and test sets. Additionally, the different immune microenvironment status of patients in the high- and low-risk groups, suggesting that patients in the low-risk group may be more sensitive to immunotherapy, particularly immune checkpoint inhibitors. Finally, we found that depletion of ATP2A1, one of the risk genes in our model, influence the biologic behaviour of CRC cells significantly. Conclusion: The m 7 G-related DDR genes can be used as important markers for predicting patient prognosis and immunotherapy response. Our data suggest that ATP2A1 may promote the proliferation of colon cancer cells. These findings may provide new therapeutic targets for the treatment of colon cancer.
    Materialart: Online-Ressource
    ISSN: 1664-8021
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606823-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-2-7)
    Kurzfassung: Objective: This study aims to explore the clinical characteristics and genetic basis of a patient with unilateral ptosis and unilateral hearing impairment in pedigree analysis. Methods: The clinical data of the child and his father were collected. The genomic DNA of the patient and his relatives were extracted from their peripheral blood samples and subjected to trio-whole-exome sequencing (trio-WES) and copy number variation analysis. Sanger sequencing was used to verify the potential variant. Results: The sequencing analysis identified a heterozygous nonsense variant c.6431C & gt; A (p.Ser2144*) in the ZNF462 gene (NM_021224.6) in the child and his father, whereas the locus in his asymptomatic mother, brother, and grandparents was found to be the wild type, which is an autosomal dominant inheritance. The new genetic variant has not been previously reported in the ClinVar and HGMD databases and the Genome Aggregation Database (gnomAD). Conclusion: This is the first incidence of Weiss–Kruszka syndrome relating to the nonsense variant in the ZNF462 gene in China. The finding from this study is novel in its expansion of the variant spectrum of the ZNF462 gene and clarifies the genetic etiology of the patient and his father.
    Materialart: Online-Ressource
    ISSN: 1664-8021
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606823-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurorobotics Vol. 16 ( 2022-12-2)
    In: Frontiers in Neurorobotics, Frontiers Media SA, Vol. 16 ( 2022-12-2)
    Kurzfassung: Wheel-legged robots have fast and stable motion characteristics on flat roads, but there are the problems of poor balance ability and low movement level in special terrains such as rough roads. In this paper, a new type of wheel-legged robot with parallel four-bar mechanism is proposed, and the linear quadratic regulator (LQR) controller and fuzzy proportion differentiation (PD) jumping controller are designed and developed to achieve stable motion so that the robot has the ability to jump over obstacles and adapt to rough terrain. The amount of energy released by the parallel four-bar linkage mechanism changes with the change of the link angle, and the height of the jump trajectory changes accordingly, which improves the robot’s ability to overcome obstacles facing vertical obstacles. Simulations and real scene tests are performed in different terrain environments to verify obstacle crossing capabilities. The simulation results show that, in the pothole terrain, the maximum height error of the two hip joint motors is 2 mm for the obstacle surmounting method of the adaptive retractable wheel-legs; in the process of single leg obstacle surmounting, the maximum height error of the hip joint motors is only 6.6 mm. The comparison of simulation data and real scene experimental results shows that the robot has better robustness in moving under complex terrains.
    Materialart: Online-Ressource
    ISSN: 1662-5218
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2453002-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-12-5)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-12-5)
    Kurzfassung: Obstructive sleep apnea (OSA) is a globally prevalent disease closely associated with hypertension. To date, no predictive model for OSA-related hypertension has been established. We aimed to use machine learning (ML) to construct a model to analyze risk factors and predict OSA-related hypertension. Materials and methods We retrospectively collected the clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 and randomly divided them into training and validation sets. A total of 1,493 OSA patients with 27 variables were included. Independent risk factors for the risk of OSA-related hypertension were screened by the multifactorial logistic regression models. Six ML algorithms, including the logistic regression (LR), the gradient boosting machine (GBM), the extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), bootstrapped aggregating (Bagging), and the multilayer perceptron (MLP), were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model. We compared the accuracy and discrimination of the models to identify the best machine learning algorithm for predicting OSA-related hypertension. In addition, a web-based tool was developed to promote its clinical application. We used permutation importance and Shapley additive explanations (SHAP) to determine the importance of the selected features and interpret the ML models. Results A total of 18 variables were selected for the models. The GBM model achieved the most extraordinary discriminatory ability (area under the receiver operating characteristic curve = 0.873, accuracy = 0.885, sensitivity = 0.713), and on the basis of this model, an online tool was built to help clinicians optimize OSA-related hypertension patient diagnosis. Finally, age, family history of hypertension, minimum arterial oxygen saturation, body mass index, and percentage of time of SaO 2 & lt; 90% were revealed by the SHAP method as the top five critical variables contributing to the diagnosis of OSA-related hypertension. Conclusion We established a risk prediction model for OSA-related hypertension patients using the ML method and demonstrated that among the six ML models, the gradient boosting machine model performs best. This prediction model could help to identify high-risk OSA-related hypertension patients, provide early and individualized diagnoses and treatment plans, protect patients from the serious consequences of OSA-related hypertension, and minimize the burden on society.
    Materialart: Online-Ressource
    ISSN: 2297-055X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2781496-8
    Standort Signatur Einschränkungen Verfügbarkeit
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