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  • Springer Science and Business Media LLC  (43)
  • 1
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-07-20)
    Abstract: The unique dumbbell-shape of grass guard cells (GCs) is controlled by their cell walls which enable their rapid responses to the environment. The molecular mechanisms regulating the synthesis and assembly of GC walls are as yet unknown. Here we have identified BZU3 , a maize gene encoding UDP-glucose 4-epimerase that regulates the supply of UDP-glucose during GC wall synthesis. The BZU3 mutation leads to significant decreases in cellular UDP-glucose levels. Immunofluorescence intensities reporting levels of cellulose and mixed-linkage glucans are reduced in the GCs, resulting in impaired local wall thickening. BZU3 also catalyzes the epimerization of UDP-N-acetylgalactosamine to UDP-N-acetylglucosamine, and the BZU3 mutation affects N-glycosylation of proteins that may be involved in cell wall synthesis and signaling. Our results suggest that the spatiotemporal modulation of BZU3 plays a dual role in controlling cell wall synthesis and glycosylation via controlling UDP-glucose/N-acetylglucosamine homeostasis during stomatal morphogenesis. These findings provide insights into the mechanisms controlling formation of the unique morphology of grass stomata.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 2
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-06-29)
    Abstract: Hashimoto’s thyroiditis (HT) is the main cause of hypothyroidism. We develop a deep learning model called HTNet for diagnosis of HT by training on 106,513 thyroid ultrasound images from 17,934 patients and test its performance on 5051 patients from 2 datasets of static images and 1 dataset of video data. HTNet achieves an area under the receiver operating curve (AUC) of 0.905 (95% CI: 0.894 to 0.915), 0.888 (0.836–0.939) and 0.895 (0.862–0.927). HTNet exceeds radiologists’ performance on accuracy (83.2% versus 79.8%; binomial test, p   〈  0.001) and sensitivity (82.6% versus 68.1%; p   〈  0.001). By integrating serologic markers with imaging data, the performance of HTNet was significantly and marginally improved on the video (AUC, 0.949 versus 0.888; DeLong’s test, p  = 0.004) and static-image (AUC, 0.914 versus 0.901; p  = 0.08) testing sets, respectively. HTNet may be helpful as a tool for the management of HT.
    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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  • 3
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-06-25)
    Abstract: Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi -associated taurine depletion as a key factor in the pathogenesis of UIAs.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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  • 4
    In: Journal of Intensive Care, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2021-12)
    Abstract: Immune and inflammatory dysfunction was reported to underpin critical COVID-19(coronavirus disease 2019). We aim to develop a machine learning model that enables accurate prediction of critical COVID-19 using immune-inflammatory features at admission. Methods We retrospectively collected 2076 consecutive COVID-19 patients with definite outcomes (discharge or death) between January 27, 2020 and March 30, 2020 from two hospitals in China. Critical illness was defined as admission to intensive care unit, receiving invasive ventilation, or death. Least Absolute Shrinkage and Selection Operator (LASSO) was applied for feature selection. Five machine learning algorithms, including Logistic Regression (LR), Support Vector Machine (SVM), Gradient Boosted Decision Tree (GBDT), K-Nearest Neighbor (KNN), and Neural Network (NN) were built in a training dataset, and assessed in an internal validation dataset and an external validation dataset. Results Six features (procalcitonin, [T + B + NK cell] count, interleukin 6, C reactive protein, interleukin 2 receptor, T-helper lymphocyte/T-suppressor lymphocyte) were finally used for model development. Five models displayed varying but all promising predictive performance. Notably, the ensemble model, SPMCIIP (severity prediction model for COVID-19 by immune-inflammatory parameters), derived from three contributive algorithms (SVM, GBDT, and NN) achieved the best performance with an area under the curve (AUC) of 0.991 (95% confidence interval [CI] 0.979–1.000) in internal validation cohort and 0.999 (95% CI 0.998–1.000) in external validation cohort to identify patients with critical COVID-19. SPMCIIP could accurately and expeditiously predict the occurrence of critical COVID-19 approximately 20 days in advance. Conclusions The developed online prediction model SPMCIIP is hopeful to facilitate intensive monitoring and early intervention of high risk of critical illness in COVID-19 patients. Trial registration This study was retrospectively registered in the Chinese Clinical Trial Registry ( ChiCTR2000032161 ). Graphical abstracthelper lymphocytve vv
    Type of Medium: Online Resource
    ISSN: 2052-0492
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2739853-5
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  • 5
    In: Signal Transduction and Targeted Therapy, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2020-03-13)
    Abstract: Internal tandem duplication (ITD) mutations of FMS-like tyrosine kinase-3 (FLT3) are the most frequent genetic alterations in acute myeloid leukemia (AML) and predict a poor prognosis. FLT3 tyrosine kinase inhibitors (TKIs) provide short-term clinical responses, but the long-term prognosis of FLT3/ITD + AML patients remains poor. Notch signaling is important in numerous types of tumors. However, the role of Notch signaling in FLT3/ITD + AML remains to be elucidated. In the current study, we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD + cell lines and primary cells. As Notch signaling can be blocked by γ-secretase inhibitors (GSIs), we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD + AML and explored the underlying molecular mechanisms. As a result, we observed synergistic cytotoxic effects, and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD + AML cell lines and in primary AML cells. Furthermore, the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD + patient-derived xenograft AML model. Mechanistically, differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy, possibly through ERK signaling. Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD + AML.
    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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  • 6
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-11-18)
    Abstract: Long non-coding RNAs (lncRNAs), functioning as competing endogenous RNAs (ceRNAs), have been reported to play important roles in the pathogenesis of autoimmune diseases. However, little is known about the regulatory roles of lncRNAs underlying the mechanism of myasthenia gravis (MG). The aim of the present study was to explore the roles of lncRNAs as ceRNAs associated with the progression of MG. Methods MG risk genes and miRNAs were obtained from public databases. Protein–protein interaction (PPI) network analysis and module analysis were performed. A lncRNA-mediated module-associated ceRNA (LMMAC) network, which integrated risk genes in modules, risk miRNAs and predicted lncRNAs, was constructed to systematically explore the regulatory roles of lncRNAs in MG. Through performing random walk with restart on the network, HCG18/miR-145-5p/CD28 ceRNA axis was found to play important roles in MG, potentially. The expression of HCG18 in MG patients was detected using RT-PCR. The effects of HCG18 knockdown on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry. The interactions among HCG18, miR-145-5p and CD28 were explored by luciferase assay, RT-PCR and western blot assay. Results Based on PPI network, we identified 9 modules. Functional enrichment analyses revealed these modules were enriched in immune-related signaling pathways. We then constructed LMMAC network, containing 25 genes, 50 miRNAs, and 64 lncRNAs. Through bioinformatics algorithm, we found lncRNA HCG18 as a ceRNA, might play important roles in MG. Further experiments indicated that HCG18 was overexpressed in MG patients and was a target of miR-145-5p. Functional assays illustrated that HCG18 suppressed Jurkat cell apoptosis and promoted cell proliferation. Mechanistically, knockdown of HCG18 inhibited the CD28 mRNA and protein expression levels in Jurkat cells, while miR-145-5p inhibitor blocked the reduction of CD28 expression induced by HCG18 suppression. Conclusion We have reported a novel HCG18/miR-145-5p/CD28 ceRNA axis in MG. Our findings will contribute to a deeper understanding of the molecular mechanism of and provide a novel potential therapeutic target for MG.
    Type of Medium: Online Resource
    ISSN: 1479-5876
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2118570-0
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  • 7
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-02-22)
    Abstract: Chimeric antigen receptor T-cell therapy (CAR-T) has yielded unprecedented efficacy in B-cell malignancies. With the increasing use of CAR-T-cell therapy, infection has become one of the major concerns after CAR-T-cell infusion. Some patients even develop refractory or recurrent infections, posing challenges in treatment, prophylactic, and monitoring strategies. However, the mechanisms underlying the development of these infections were not clear. Case presentation We report two cases of infection after CAR-T-cell therapy. Patient 1, diagnosed with multiple myeloma, received anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T)-cell therapy. He developed a refractory urinary infection lasting for over 5 weeks, which was caused by Candida albicans . Whole-exome sequencing revealed that he had an IL-17RA gene mutation. Patient 2, diagnosed with acute lymphoblastic B-cell leukaemia, received anti-CD19 and anti-CD22 CAR-T-cell cocktail therapy and remained in complete remission for over 4 years. The patient had pneumonia five times during the 4 years. Whole-exon sequencing revealed that he had a CX3CR1 gene mutation. Conclusion For patients who develop persistent or recurrent infections after CAR-T-cell therapy, it is recommended to screen for immunodeficiency-related gene mutations, and the results may contribute to the management of infections post-CAR-T treatment.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041550-3
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  • 8
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2015-01-28)
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 2615211-3
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2011
    In:  The Chinese-German Journal of Clinical Oncology Vol. 10, No. 12 ( 2011-12), p. 726-729
    In: The Chinese-German Journal of Clinical Oncology, Springer Science and Business Media LLC, Vol. 10, No. 12 ( 2011-12), p. 726-729
    Type of Medium: Online Resource
    ISSN: 1610-1979 , 1613-9089
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2011
    detail.hit.zdb_id: 2157135-1
    SSG: 6,25
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  • 10
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-08-25)
    Abstract: Insecticide resistance can arise from a variety of mechanisms, including changes to the target site, but is often associated with substantial fitness costs to insects. Here we describe two resistance-associated target-site mutations that have synergistic and compensatory effects that combine to produce high and persistent levels of resistance to fipronil, an insecticide targeting on γ-aminobytyric acid (GABA) receptors. In Nilaparvata lugens , a major pest of rice crops in many parts of Asia, we have identified a single point mutation (A302S) in the GABA receptor RDL that has been identified previously in other species and which confers low levels of resistance to fipronil (23-fold) in N. lugans . In addition, we have identified a second resistance-associated RDL mutation (R300Q) that, in combination with A302S, is associated with much higher levels of resistance (237-fold). The R300Q mutation has not been detected in the absence of A302S in either laboratory-selected or field populations, presumably due to the high fitness cost associated with this mutation. Significantly, it appears that the A302S mutation is able to compensate for deleterious effects of R300Q mutation on fitness cost. These findings identify a novel resistance mechanism and may have important implications for the spread of insecticide resistance.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2615211-3
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