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  • 1
    Online Resource
    Online Resource
    Simulation and design for stratified iron fiber absorbing materials
    Elsevier BV ; 2002
    In:  Materials & Design Vol. 23, No. 1 ( 2002-2), p. 51-57
    Details
    In: Materials & Design, Elsevier BV, Vol. 23, No. 1 ( 2002-2), p. 51-57
    Type of Medium: Online Resource
    ISSN: 0261-3069
    URL: Article
    DOI: 10.1016/S0261-3069(01)00042-5
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2002
    detail.hit.zdb_id: 2015480-X
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  • 2
    Online Resource
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    The gut microbiome in atherosclerotic cardiovascular disease
    Springer Science and Business Media LLC ; 2017
    In:  Nature Communications Vol. 8, No. 1 ( 2017-10-10)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-10-10)
    Abstract: The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-017-00900-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2553671-0
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  • 3
    Online Resource
    Online Resource
    Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study
    Informa UK Limited ; 2022
    In:  Gut Microbes Vol. 14, No. 1 ( 2022-12-31)
    Details
    In: Gut Microbes, Informa UK Limited, Vol. 14, No. 1 ( 2022-12-31)
    Type of Medium: Online Resource
    ISSN: 1949-0976 , 1949-0984
    URL: Article
    DOI: 10.1080/19490976.2021.2003176
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2575755-6
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  • 4
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    Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients
    Springer Science and Business Media LLC ; 2021
    In:  Cell Discovery Vol. 7, No. 1 ( 2021-04-13)
    Details
    In: Cell Discovery, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2021-04-13)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis , or Mycoplasma spp . (including M. hominis and M. orale ). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.
    Type of Medium: Online Resource
    ISSN: 2056-5968
    URL: Article
    DOI: 10.1038/s41421-021-00257-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2842548-0
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  • 5
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    Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)
    Springer Science and Business Media LLC ; 2020
    In:  Nature Communications Vol. 11, No. 1 ( 2020-10-06)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-10-06)
    Abstract: Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89] %) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44] %, −0.53[−0.68, −0.37]%, P  〈  0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii . Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-020-18414-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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  • 6
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    Upper airway lengthening caused by weight increase in obstructive sleep apnea patients
    Springer Science and Business Media LLC ; 2020
    In:  Respiratory Research Vol. 21, No. 1 ( 2020-12)
    Details
    In: Respiratory Research, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2020-12)
    Abstract: The longer upper airway is more collapsible during sleep. This study aims to reveal relationships among upper airway length, weight, and obstructive sleep apnea (OSA), particularly to answer why the upper airway of OSA patients is longer than that of healthy people and why some obese people suffer from OSA while others do not. Methods We perform head and neck MRI on male patients and controls, and measure 〉  20 morphological parameters, including several never before investigated, to quantify the effect of weight change on upper airway length. Results The upper airway length is longer in patients and correlates strongly to body weight. Weight increase leads to significant fat infiltration in the tongue, causing the hyoid to move downward and lengthen the airway in patients. The apnea-hypopnea index (AHI) strongly correlates to airway length and tongue size. Surprisingly, a distance parameter h and angle β near the occipital bone both show significant differences between healthy males and patients due to their different head backward tilt angle, and strongly correlates with AHI. The contributions of downward hyoid movement and head tilt on airway lengthening are 67.4–80.5% and19.5–32.6%, respectively, in patients. The parapharyngeal fat pad also correlates strongly with AHI. Conclusions The findings in this study reveal that the amount of body weight and distribution of deposited fat both affect airway length, and therefore OSA. Fat distribution plays a larger impact than the amount of weight, and is a better predictor of who among obese people are more prone to OSA.
    Type of Medium: Online Resource
    ISSN: 1465-993X
    URL: Article
    DOI: 10.1186/s12931-020-01532-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041675-1
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  • 7
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    Multiple approaches for massively parallel sequencing of SARS-CoV-2 genomes directly from clinical samples
    Springer Science and Business Media LLC ; 2020
    In:  Genome Medicine Vol. 12, No. 1 ( 2020-12)
    Details
    In: Genome Medicine, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2020-12)
    Abstract: COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses. Methods We applied a novel multiplex PCR amplicon (amplicon)-based and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of SARS-CoV-2 from serials dilutions of a cultured isolate, and eight clinical samples covering a range of sample types and viral loads. We also examined and compared the sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. Results We demonstrated that both amplicon and capture methods efficiently enriched SARS-CoV-2 content from clinical samples, while the enrichment efficiency of amplicon outran that of capture in more challenging samples. We found that capture was not as accurate as meta and amplicon in identifying between-sample variations, whereas amplicon method was not as accurate as the other two in investigating within-sample variations, suggesting amplicon sequencing was not suitable for studying virus-host interactions and viral transmission that heavily rely on intra-host dynamics. We illustrated that meta uncovered rich genetic information in the clinical samples besides SARS-CoV-2, providing references for clinical diagnostics and therapeutics. Taken all factors above and cost-effectiveness into consideration, we proposed guidance for how to choose sequencing strategy for SARS-CoV-2 under different situations. Conclusions This is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses.
    Type of Medium: Online Resource
    ISSN: 1756-994X
    URL: Article
    DOI: 10.1186/s13073-020-00751-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2484394-5
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  • 8
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    Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia
    Springer Science and Business Media LLC ; 2023
    In:  BMC Medicine Vol. 21, No. 1 ( 2023-07-27)
    Details
    In: BMC Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-07-27)
    Abstract: Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. Methods Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients ( n  = 184) from heterozygous FH (HeFH, n  = 376) and non-FH ( n  = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. Results Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. Conclusions Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.
    Type of Medium: Online Resource
    ISSN: 1741-7015
    URL: Article
    DOI: 10.1186/s12916-023-02967-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2131669-7
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  • 9
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    Metagenomic analysis reveals crosstalk between gut microbiota and glucose-lowering drugs targeting the gastrointestinal tract in Chinese patients with type 2 diabetes: a 6 month, two-arm randomised trial
    Springer Science and Business Media LLC ; 2022
    In:  Diabetologia Vol. 65, No. 10 ( 2022-10), p. 1613-1626
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 65, No. 10 ( 2022-10), p. 1613-1626
    Abstract: The use of oral glucose-lowering drugs, particularly those designed to target the gut ecosystem, is often observed in association with altered gut microbial composition or functional capacity in individuals with type 2 diabetes. The gut microbiota, in turn, plays crucial roles in the modulation of drug efficacy. We aimed to assess the impacts of acarbose and vildagliptin on human gut microbiota and the relationships between pre-treatment gut microbiota and therapeutic responses. Methods This was a randomised, open-labelled, two-arm trial in treatment-naive type 2 diabetes patients conducted in Beijing between December 2016 and December 2017. One hundred participants with overweight/obesity and newly diagnosed type 2 diabetes were recruited from the Pinggu Hospital and randomly assigned to the acarbose ( n =50) or vildagliptin ( n =50) group using sealed envelopes. The treatment period was 6 months. Blood, faecal samples and visceral fat data from computed tomography images were collected before and after treatments to measure therapeutic outcomes and gut microbiota. Metagenomic datasets from a previous type 2 diabetes cohort receiving acarbose or glipizide for 3 months were downloaded and processed. Statistical analyses were applied to identify the treatment-related changes in clinical variables, gut microbiota and associations. Results Ninety-two participants were analysed. After 6 months of acarbose ( n =44) or vildagliptin ( n =48) monotherapy, both groups achieved significant reductions in HbA 1c (from 60 to 46 mmol/mol [from 7.65% to 6.40%] in the acarbose group and from 59 to 44 mmol/mol [from 7.55% to 6.20%] in the vildagliptin group) and visceral fat areas (all adjusted p values for pre–post comparisons 〈 0.05). Both arms showed drug-specific and shared changes in relative abundances of multiple gut microbial species and pathways, especially the common reductions in Bacteroidetes species. Three months and 6 months of acarbose-induced changes in microbial composition were highly similar in type 2 diabetes patients from the two independent studies. Vildagliptin treatment significantly enhanced fasting active glucagon-like peptide-1 (GLP-1) levels. Baseline gut microbiota, rather than baseline GLP-1 levels, were strongly associated with GLP-1 response to vildagliptin, and to a lesser extent with GLP-1 response to acarbose. Conclusions/interpretation This study reveals common microbial responses in type 2 diabetes patients treated with two glucose-lowering drugs targeting the gut differently and acceptable performance of baseline gut microbiota in classifying individuals with different GLP-1 responses to vildagliptin. Our findings highlight bidirectional interactions between gut microbiota and glucose-lowering drugs. Trial registration ClinicalTrials.gov NCT02999841 Funding National Key Research and Development Project: 2016YFC1304901. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-022-05768-5
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458993-X
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  • 10
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    The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression
    Springer Science and Business Media LLC ; 2016
    In:  Cell Death & Disease Vol. 7, No. 12 ( 2016-12-29), p. e2571-e2571
    Details
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 7, No. 12 ( 2016-12-29), p. e2571-e2571
    Abstract: The function of activating transcription factor 1 (ATF1) and the mechanism about why ATF1 was over-phosphorylated in nasopharyngeal carcinoma (NPC) progression is completely undiscovered. In this study, a series of experiments both in vitro and in vivo were used to characterize a promotive function of ATF1 in NPC tumorigenesis and identify prolyl isomerase Pin1 as a novel regulator of ATF1 at post-transcription. First, we found that overexpression of ATF1 promoted colony formation in NPC. However, the high protein level of ATF1 in NPC was not resulted from high mRNA level. Then, a direct interaction between Pin1 and ATF1 at Thr184 was demonstrated using mammalian two-hybrid assay and coimmunoprecipitation. Cycloheximide (CHX) treatment indicated Pin1 stabilized the expression of ATF1 at post-transcription level. We confirmed that Pin1 upregulated ATF1 transcriptional activity of Bcl-2 using luciferase reporter assay, quantitative RT-PCR and western blot. Furthermore, the newly identified phosphorylation of ATF1 at Thr184 was suggested to have an important role in ATF1 function of transcription and tumor promotion. Finally, high expression of Pin1 in NPC tissue was found to be positively correlated with ATF1. The ATF1 promoted NPC tumorigenesis was regulated by Pin1 both in vitro and in vivo. All these findings clearly state that Pin1 is a novel regulator of ATF1 at Thr184 and thereby enhances ATF1 transcription activity and tumorigenesis promotive function in NPC.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    URL: Article
    DOI: 10.1038/cddis.2016.349
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2541626-1
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