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  • 1
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-03-18)
    Abstract: Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called “calcification paradox”. Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 2
    In: Signal Transduction and Targeted Therapy, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2020-09-18)
    Abstract: Although stress has been known to increase the susceptibility of pathogen infection, the underlying mechanism remains elusive. In this study, we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus (H1N1) and obviously aggravated lung inflammation. Corticosterone (CORT), a main type of glucocorticoids in rodents, was secreted in the plasma of stressed mice. We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling (MAVS) protein-transduced IFN-β production without affecting its mRNA level, while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice. Mechanistically, the effect of CORT was mediated by proteasome-dependent degradation of MAVS, thereby resulting in the impediment of MAVS-transduced IFN-β generation in vivo and in vitro. Furthermore, RNA-seq assay results indicated the involvement of Mitofusin 2 (Mfn2) in this process. Gain- and loss-of-function experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS. Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2 (HR1), MAVS (C-terminal/TM) and SYVN1 (TM). Collectively, our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a ‘fine tuning’ of antiviral innate immunity in response to influenza infection under stress.
    Type of Medium: Online Resource
    ISSN: 2059-3635
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2886872-9
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  • 3
    In: Bone Research, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2023-08-16)
    Abstract: Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells (HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using siRNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition. Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.
    Type of Medium: Online Resource
    ISSN: 2095-6231
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2803313-9
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  • 4
    In: Toxicology and Applied Pharmacology, Elsevier BV, Vol. 408 ( 2020-12), p. 115261-
    Type of Medium: Online Resource
    ISSN: 0041-008X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1471923-X
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  • 5
    In: Life Sciences, Elsevier BV, Vol. 256 ( 2020-09), p. 117884-
    Type of Medium: Online Resource
    ISSN: 0024-3205
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2013911-1
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-8-29)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-29)
    Abstract: Kinesin is a molecular motor for transporting “goods” within cells and plays a key role in many types of tumors. The multi-angle study of kinesin at the pan-cancer level is conducive to understanding its role in tumorigenesis and development and clinical treatment potential. Methods We evaluated the expression of KIF genes, performed differential analysis by using the R package limma, and explored the pan-cancer prognosis of KIF genes by univariate Cox regression analysis. To evaluate the pan-cancer role of KIF genes as a whole, we defined the KIFscore with the help of gene set variation analysis (GSVA) and explored the KIFscores across normal tissues, tumor cell lines, and 33 tumor types in TCGA. Next, we used spearman correlation analysis to extensively study the correlation between the KIFscore and tumor prognosis and be-tween the KIFscore and clinical indicators. We also identified the relationship between the KIFscore and genomic variation and immune molecular signatures by multiplatform analysis. Finally, we identified the key genes in clear cell renal cell carcinoma (ccRCC) through machine learning algorithms and verified the candidate genes by CCK8, wound healing assay, Transwell assay, and flow cytometry. Results In most cancers, KIFscores are high and they act as a risk factor for cancer. The KIFscore was significantly associated with copy number variation (CNV), tumor mutation burden (TMB), immune subtypes, DNA repair deficiency, and tumor stemness indexes. Moreover, in almost all cancer species, the KIFscore was positively correlated with T cell CD4+ TH2, the common lymphoid pro-genitor, and the T cell follicular helper. In addition, it was negatively correlated with CXCL16, CCL14, TNFSF13, and TNFRSF14 and positively correlated with ULBP1, MICB, and CD276. Machine learning helped us to identify four hub-genes in ccRCC. The suitable gene, KIF14, is highly expressed in ccRCC and promotes tumor cell proliferation, migration, and invasion. Conclusion Our study shows that the KIF genes play an important pan-cancer role and may become a potential new target for a variety of tumor treatments in the future. Furthermore, KIF14, a key molecule in the KIF genes, can provide a new idea for the ccRCC treatment.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-3-7)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-3-7)
    Abstract: Diabetic kidney disease (DKD) is a long-term complication of diabetes and causes renal microvascular disease. It is also one of the main causes of end-stage renal disease (ESRD), which has a complex pathophysiological process. Timely prevention and treatment are of great significance for delaying DKD. This study aimed to use bioinformatics analysis to find key diagnostic markers that could be possible therapeutic targets for DKD. Methods We downloaded DKD datasets from the Gene Expression Omnibus (GEO) database. Overexpression enrichment analysis (ORA) was used to explore the underlying biological processes in DKD. Algorithms such as WGCNA, LASSO, RF, and SVM_RFE were used to screen DKD diagnostic markers. The reliability and practicability of the the diagnostic model were evaluated by the calibration curve, ROC curve, and DCA curve. GSEA analysis and correlation analysis were used to explore the biological processes and significance of candidate markers. Finally, we constructed a mouse model of DKD and diabetes mellitus (DM), and we further verified the reliability of the markers through experiments such as PCR, immunohistochemistry, renal pathological staining, and ELISA. Results Biological processes, such as immune activation, T-cell activation, and cell adhesion were found to be enriched in DKD. Based on differentially expressed oxidative stress and inflammatory response-related genes (DEOIGs), we divided DKD patients into C1 and C2 subtypes. Four potential diagnostic markers for DKD, including tenascin C, peroxidasin, tissue inhibitor metalloproteinases 1, and tropomyosin (TNC, PXDN, TIMP1, and TPM1, respectively) were identified using multiple bioinformatics analyses. Further enrichment analysis found that four diagnostic markers were closely related to various immune cells and played an important role in the immune microenvironment of DKD. In addition, the results of the mouse experiment were consistent with the bioinformatics analysis, further confirming the reliability of the four markers. Conclusion In conclusion, we identified four reliable and potential diagnostic markers through a comprehensive and systematic bioinformatics analysis and experimental validation, which could serve as potential therapeutic targets for DKD. We performed a preliminary examination of the biological processes involved in DKD pathogenesis and provide a novel idea for DKD diagnosis and treatment.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 8
    In: International Journal of Climatology, Wiley
    Abstract: The uneven changes in potential evapotranspiration (PET) in response to temperature rise are called the ‘evapotranspiration paradox’ phenomenon, which is expected to intensify further under a warming climate. In this paper, we explored the spatial–temporal changes in the future ‘evapotranspiration paradox’ phenomenon over China and its 10 major river sub‐regions under different climate change scenarios. Thus, this paper uses four global climate model outputs under seven shared socioeconomic pathway‐based scenarios (SSP1‐1.9, SSP1‐2.6, SSP2‐4.5, SSP3‐7.0, SSP4‐3.4, SSP4‐6.0 and SSP5‐8.5) from the sixth phase of the Coupled Model Intercomparison Project (CMIP6). Considering the latest IPCC's 6th Assessment Report (AR6), this research emphasizes the 2021–2040 (near‐term), 2041–2060 (mid‐term) and 2081–2100 (long‐term) periods to anticipate the ‘evapotranspiration paradox’ phenomenon. In this study, PET is estimated based on the modified Penman–Monteith (P‐M) method (considering CO 2 ). Furthermore, the paradox phenomenon in this study is defined considering two pivotal conditions: the surface temperature increases but the evaporation decreases (Type I), and the temperature decreases but the evaporation still tends to increase (Type II). The results show that there were only Type I ‘evapotranspiration paradoxes’ that existed in the historical period, which were dominant especially before the 1990s. Nearly 50% of the areas experienced the Type I ‘evapotranspiration paradox’ phenomenon that occurred during 1975–1994 and 1995–2014. Spatially, it covered 100% of the area of the Southeast River (SER) and the Liaohe River (LR) during 1975–1994 and the area of the SER, the HAR, the HHR and the LR during 1995–2014. In the future, the interdecadal growth rate of PET in China is projected to be the highest under the SSP5‐8.5 and the lowest under the SSP3‐7.0 with spatial variation. Importantly, the largest areas of approximately 36% and 45% with the Type I phenomenon are inclined to occur under the SSP1‐1.9 and SSP4‐6.0, respectively, over the long‐term period (2081–2100). The area with the Type I phenomenon will be less than 20% in the near‐term, and it is less than 12% in the mid‐term period. For the Type II evapotranspiration paradox, the uppermost 45% of the area is expected to experience the Type II phenomenon under SSP1‐1.9 during the mid‐term period, while it is 30% under SSP1‐2.6 during the long‐term period. However, this study's findings provide the scientific basis for formulating adaptation and mitigation strategies to combat ‘evapotranspiration paradox’‐related extremes at regional scales.
    Type of Medium: Online Resource
    ISSN: 0899-8418 , 1097-0088
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1491204-1
    SSG: 14
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  • 9
    Online Resource
    Online Resource
    China Science Publishing & Media Ltd. ; 2013
    In:  Journal of Fishery Sciences of China Vol. 18, No. 6 ( 2013-9-4), p. 1308-1314
    In: Journal of Fishery Sciences of China, China Science Publishing & Media Ltd., Vol. 18, No. 6 ( 2013-9-4), p. 1308-1314
    Type of Medium: Online Resource
    ISSN: 1005-8737
    Language: English
    Publisher: China Science Publishing & Media Ltd.
    Publication Date: 2013
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  • 10
    Online Resource
    Online Resource
    Royal Society of Chemistry (RSC) ; 2014
    In:  CrystEngComm Vol. 16, No. 44 ( 2014), p. 10314-10320
    In: CrystEngComm, Royal Society of Chemistry (RSC), Vol. 16, No. 44 ( 2014), p. 10314-10320
    Type of Medium: Online Resource
    ISSN: 1466-8033
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2014
    detail.hit.zdb_id: 2025075-7
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