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  • 1
    Online Resource
    Online Resource
    5mC-Related lncRNAs as Potential Prognostic Biomarkers in Colon Adenocarcinoma
    MDPI AG ; 2022
    In:  Biology Vol. 11, No. 2 ( 2022-02-01), p. 231-
    Details
    In: Biology, MDPI AG, Vol. 11, No. 2 ( 2022-02-01), p. 231-
    Abstract: Globally, colon adenocarcinoma (COAD) is one of the most frequent types of malignant tumors. About 40~50% of patients with advanced colon adenocarcinoma die from recurrence and metastasis. Long non-coding RNAs (lncRNAs) and 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of COAD. The goal of this study was to explore the biological characteristics and potential predictive value of 5mC-related lncRNA signature in COAD. In this research, The Cancer Genome Atlas (TCGA) was utilized to obtain the expression of genes and somatic mutations in COAD, and Pearson correlation analysis was used to select lncRNAs involved in 5mC-regulated genes. Furthermore, we applied univariate Cox regression and Lasso Cox regression to construct 5mC-related lncRNA signature. Then Kaplan–Meier survival analysis, principal components analysis (PCA), receiver operating characteristic (ROC) curve, and a nomogram were performed to estimate the prognostic effect of the risk signature. GSEA was utilized to predict downstream access of the risk signature. Finally, the immune characteristics and immunotherapeutic signatures targeting this risk signature were analyzed. In the results, we obtained 1652 5mC-related lncRNAs by Pearson correlation analysis in the TCGA database. Next, we selected a risk signature that comprised 4 5mC-related lncRNAs by univariate and Lasso Cox regression. The prognostic value of the risk signature was proven. Finally, the biological mechanism and potential immunotherapeutic response of the risk signature were identified. Collectively, we constructed the 5mC-related lncRNA risk signature, which could provide a novel prognostic prediction of COAD patients.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology11020231
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661517-4
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  • 2
    Online Resource
    Online Resource
    The phosphate-induced small RNA EsrL promotes E. coli virulence, biofilm formation, and intestinal colonization
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Signaling Vol. 16, No. 767 ( 2023-01-10)
    Details
    In: Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 16, No. 767 ( 2023-01-10)
    Abstract: To cause disease, enterohemorrhagic E. coli (EHEC) and enteropathogenic E. coli (EPEC) must first adhere to intestinal cells (enterocytes). Adhesion requires the expression of genes in the LEE pathogenicity island driven by the master regulator Ler. Jia et al. identified a small RNA, EsrL, that promoted EHEC and EPEC adhesion to cultured human cells and EHEC colonization of the rabbit colon. Under high-phosphate conditions similar to those in the gut, EsrL expression was derepressed and EsrL bound to and stabilized the ler transcript. Stabilization of another transcript by EsrL ultimately enhanced the capacity of EPEC and nonpathogenic E. coli to form biofilms, which protects the bacteria from antibiotics and host defenses. Stabilization of both transcripts likely contributes to E. coli virulence and biofilm formation in the high-phosphate environment of the gut.–AMV
    Type of Medium: Online Resource
    ISSN: 1945-0877 , 1937-9145
    URL: Article
    DOI: 10.1126/scisignal.abm0488
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 3
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    Online Resource
    Spectroscopic evidence of bilayer splitting and strong interlayer pairing in the superconductor KCa 2 Fe 4 As 4 F 2
    American Physical Society (APS) ; 2020
    In:  Physical Review B Vol. 101, No. 22 ( 2020-6-12)
    Details
    In: Physical Review B, American Physical Society (APS), Vol. 101, No. 22 ( 2020-6-12)
    Type of Medium: Online Resource
    ISSN: 2469-9950 , 2469-9969
    URL: Article
    DOI: 10.1103/PhysRevB.101.224508
    RVK:
    UA 6500.3.B
    Language: English
    Publisher: American Physical Society (APS)
    Publication Date: 2020
    detail.hit.zdb_id: 2844160-6
    detail.hit.zdb_id: 209770-9
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  • 4
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    Online Resource
    Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer’s disease
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 27 ( 2014-07-08), p. 9959-9964
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 27 ( 2014-07-08), p. 9959-9964
    Abstract: Alzheimer’s disease (AD), characterized by cognitive decline, has emerged as a disease of synaptic failure. The present study reveals an unanticipated role of erythropoietin-producing hepatocellular A4 (EphA4) in mediating hippocampal synaptic dysfunctions in AD and demonstrates that blockade of the ligand-binding domain of EphA4 reverses synaptic impairment in AD mouse models. Enhanced EphA4 signaling was observed in the hippocampus of amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model of AD, whereas soluble amyloid-β oligomers (Aβ), which contribute to synaptic loss in AD, induced EphA4 activation in rat hippocampal slices. EphA4 depletion in the CA1 region or interference with EphA4 function reversed the suppression of hippocampal long-term potentiation in APP/PS1 transgenic mice, suggesting that the postsynaptic EphA4 is responsible for mediating synaptic plasticity impairment in AD. Importantly, we identified a small-molecule rhynchophylline as a novel EphA4 inhibitor based on molecular docking studies. Rhynchophylline effectively blocked the EphA4-dependent signaling in hippocampal neurons, and oral administration of rhynchophylline reduced the EphA4 activity effectively in the hippocampus of APP/PS1 transgenic mice. More importantly, rhynchophylline administration restored the impaired long-term potentiation in transgenic mouse models of AD. These findings reveal a previously unidentified role of EphA4 in mediating AD-associated synaptic dysfunctions, suggesting that it is a new therapeutic target for this disease.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1405803111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
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    Common (π,π) Band Folding and Surface Reconstruction in FeAs-Based Superconductors
    IOP Publishing ; 2021
    In:  Chinese Physics Letters Vol. 38, No. 5 ( 2021-06-01), p. 057404-
    Details
    In: Chinese Physics Letters, IOP Publishing, Vol. 38, No. 5 ( 2021-06-01), p. 057404-
    Abstract: High resolution angle-resolved photoemission spectroscopy (ARPES) measurements are carried out on CaKFe 4 As 4 , KCa 2 Fe 4 As 4 F 2 and (Ba 0.6 K 0.4 )Fe 2 As 2 superconductors. Clear evidence of band folding between the Brillouin zone center and corners with a ( π , π ) wave vector has been found from the measured Fermi surface and band structures in all the three kinds of superconductors. A dominant 2 × 2 surface reconstruction is observed on the cleaved surface of CaKFe 4 As 4 by scanning tunneling microscopy (STM) measurements. We propose that the commonly observed 2 × 2 reconstruction in the FeAs-based superconductors provides a general scenario to understand the origin of the ( π , π ) band folding. Our observations provide new insights in understanding the electronic structure and superconductivity mechanism in iron-based superconductors.
    Type of Medium: Online Resource
    ISSN: 0256-307X , 1741-3540
    URL: Article
    DOI: 10.1088/0256-307X/38/5/057404
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2021
    detail.hit.zdb_id: 2040565-0
    SSG: 6,25
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  • 6
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    Attachment of Enterohemorrhagic Escherichia coli to Host Cells Reduces O Antigen Chain Length at the Infection Site That Promotes Infection
    American Society for Microbiology ; 2021
    In:  mBio Vol. 12, No. 6 ( 2021-12-21)
    Details
    In: mBio, American Society for Microbiology, Vol. 12, No. 6 ( 2021-12-21)
    Abstract: Many enteropathogenic bacteria express a needle-like type III secretion system (T3SS) that translocates effectors into host cells promoting infection. O antigen (OAg) constitutes the outer layer of Gram-negative bacteria protecting bacteria from host immune responses. Shigella constitutively shortens the OAg molecule in its three-dimensional conformation by glucosylation, leading to enhanced T3SS function. However, whether and how other enteropathogenic bacteria shorten the OAg molecule that probably facilitates infection remain unknown. For the first time, we report a smart mechanism by which enterohemorrhagic Escherichia coli specifically reduces the size of the OAg molecule at the infection site upon sensing mechanical signals of intestinal epithelial cell attachment via the membrane protein YgjI. YgjI represses expression of the OAg chain length regulator gene fepE via the global regulator H-NS, leading to shortened OAg chains and injection of more T3SS effectors into host cells. However, bacteria express long-chain OAg in the intestinal lumen benefiting their survival. Animal experiments show that blocking this regulatory pathway significantly attenuates bacterial virulence. This finding enhances our understanding of interactions between the surfaces of bacterial and host cells and the way this interaction enhances bacterial pathogenesis. IMPORTANCE Little is known about the regulation of cell wall structure of enteropathogenic bacteria within the host. Here, we report that enterohemorrhagic Escherichia coli regulates its cell wall structure during the infection process, which balances its survival in the intestinal lumen and infection of intestinal epithelial cells. In the intestinal lumen, bacteria express long-chain OAg, which is located in the outer part of the cell wall, leading to enhanced resistance to antimicrobial peptides. However, upon epithelial cell attachment, bacteria sense this mechanical signal via a membrane protein and reduce the OAg chain length, resulting in enhanced injection into epithelial cells of T3SS effectors that mediate host cell infection. Similar regulation mechanisms of cell wall structure in response to host cell attachment may be widespread in pathogenic bacteria and closely related with bacterial pathogenesis.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mBio.02692-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2557172-2
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  • 7
    Online Resource
    Online Resource
    Micromixer based on Taylor dispersion
    IOP Publishing ; 2006
    In:  Journal of Physics: Conference Series Vol. 34 ( 2006-04-01), p. 136-141
    Details
    In: Journal of Physics: Conference Series, IOP Publishing, Vol. 34 ( 2006-04-01), p. 136-141
    Type of Medium: Online Resource
    ISSN: 1742-6588 , 1742-6596
    URL: Article
    DOI: 10.1088/1742-6596/34/1/023
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2006
    detail.hit.zdb_id: 2166409-2
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  • 8
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    Online Resource
    Association of hyperopia with incident clinically significant depression: epidemiological and genetic evidence in the middle-aged and older population
    BMJ ; 2022
    In:  British Journal of Ophthalmology
    Details
    In: British Journal of Ophthalmology, BMJ
    Abstract: To investigate the association between hyperopia and clinically significant depression (CSD) in middle-aged and older individuals. The effect of genetic determinants of hyperopia on incident CSD was also explored. Methods We included participants who had available data on mean spherical equivalent (MSE) and were free of depression at baseline from the UK Biobank. For the phenotypic association, hyperopia was defined as MSE of+2.00 dioptres (D) or greater, and was divided into mild, moderate and high groups. Diagnosis of CSD across follow-up was determined based on electronic hospital inpatients records. For the genetic association analysis, the association between hyperopia Polygenic Risk Score and incident CSD was assessed. Mendelian randomisation was assessed for causality association. Results Over a median follow-up of 11.11 years (IQR: 10.92–11.38), hyperopia was significantly associated with incident CSD independent of genetic risk (HR 1.29, 95% CI 1.05 to 1.59) compared with emmetropia participants, especially in those hyperopic patients without optical correction (HR 1.38, 95% CI 1.07 to 1.76). In addition, participants in the high degree of hyperopia were more likely to have incident CSD than participants in the mild degree of hyperopia (P for trend=0.009). Genetic analyses did not show any significant associations between hyperopia and incident CSD (p≥0.1). Conclusions Hyperopia was significantly associated with an increased risk of incident CSD. This was independent of genetic predisposition to hyperopia, emphasising the importance of regular vision screening and correction of hyperopia to reduce the risk of CSD regardless of genetic risk.
    Type of Medium: Online Resource
    ISSN: 0007-1161 , 1468-2079
    URL: Article
    DOI: 10.1136/bjo-2022-321876
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1482974-5
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  • 9
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    Online Resource
    A Novel Small RNA Promotes Motility and Virulence of Enterohemorrhagic Escherichia coli O157:H7 in Response to Ammonium
    American Society for Microbiology ; 2021
    In:  mBio Vol. 12, No. 2 ( 2021-04-27)
    Details
    In: mBio, American Society for Microbiology, Vol. 12, No. 2 ( 2021-04-27)
    Abstract: Enterohemorrhagic Escherichia coli serotype O157:H7 (O157) is a critical, foodborne, human intestinal pathogen that causes severe acute hemorrhagic diarrhea, abdominal cramping, and even death. Small RNAs (sRNAs) are noncoding regulatory molecules that sense environmental changes and trigger various virulence-related signaling pathways; however, few such sRNAs have been identified in O157. Here, we report a novel sRNA, EsrF that senses high ammonium concentrations in the colon and enhances O157 pathogenicity by promoting bacterial motility and adhesion to host cells. Specifically, EsrF was found to directly interact with the 5′ untranslated regions of the flagellar biosynthetic gene, flhB , mRNA and increase its abundance, thereby upregulating expression of essential flagellar genes, including flhD , flhC , fliA , and fliC , leading to elevated O157 motility and virulence. Meanwhile, an infant rabbit model of O157 infection showed that deletion of esrF and flhB significantly attenuates O157 pathogenicity. Furthermore, NtrC—the response regulator of the NtrC/B two-component system—was found to exert direct, negative regulation of esrF expression. Meanwhile, high ammonium concentrations in the colon release the inhibitory effect of NtrC on esrF , thereby enhancing its expression and subsequently promoting bacterial colonization in the host colon. Our work reveals a novel, sRNA-centered, virulence-related signaling pathway in O157 that senses high ammonium concentrations. These findings provide novel insights for future research on O157 pathogenesis and targeted treatment strategies. IMPORTANCE The process by which bacteria sense environmental cues to regulate their virulence is complex. Several studies have focused on regulating the expression of the locus of enterocyte effacement pathogenicity island in the typical gut pathogenic bacterium, O157. However, few investigations have addressed the regulation of other virulence factors in response to intestinal signals. In this study, we report our discovery of a novel O157 sRNA, EsrF, and demonstrate that it contributed to bacterial motility and virulence in vitro and in vivo through the regulation of bacterial flagellar synthesis. Furthermore, we show that high ammonium concentrations in the colon induced esrF expression to promote bacterial virulence by releasing the repression of esrF by NtrC. This study highlights the importance of sRNA in regulating the motility and pathogenicity of O157.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mBio.03605-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2557172-2
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  • 10
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    Online Resource
    Phenotypic Profiling of People With Subjective Tinnitus and Without a Clinical Hearing Loss
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular Neuroscience Vol. 16 ( 2022-2-9)
    Details
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-2-9)
    Abstract: Our objective was to study the characteristics of patients with subjective tinnitus and normal hearing and to investigate whether the features correlated to different shapes on audiograms. In this retrospective study, 313 patients with subjective tinnitus and clinically normal hearing were enrolled from the tinnitus outpatient department of the Eye and ENT Hospital of Fudan University. The following phenotypic variables were collected: age, dominant tinnitus pitch (TP), tinnitus loudness, tinnitus duration, tinnitus severity, sex, education, hearing thresholds, tinnitus position, and tinnitus condition. The dominant TPs of patients with normal hearing were mostly high-pitched, with a mean of 4866.8 ± 2579.6 Hz; thus, we speculated that the condition is related to high-frequency hearing threshold elevations. We further divided the patients into four subgroups based on the matched TP: (i) TP ≤ 500 Hz ( n = 34), (ii) 500 Hz & lt; TP ≤ 3,000 Hz ( n = 15), (iii) 3,000 Hz & lt; TP ≤ 8,000 Hz ( n = 259), and (iv) TP & gt; 8,000 Hz ( n = 5). We studied the phenotypic profiling of different audiograms and found that the group with TP of ≤500 Hz had an average “inverted-U” shaped audiogram, and the group with TP between 500 and 3,000 Hz had a slowly ascending slope audiogram below 2,000 Hz, followed by a drastically descending slope audiogram ranging from 2,000 to 8,000 Hz; further, the high-frequency (3,000–8,000 Hz) and ultra-high-frequency ( & gt;8,000 Hz) groups had flat curves below 2,000 Hz and steeper slope audiograms over 2,000 Hz. Our findings confirmed a consistency ratio between the distributions of dominant TPs and the frequencies of maximum hearing thresholds in both ears. The dominant TP was positively correlated with the maximum hearing threshold elevation frequency (left ear: r = 0.277, p & lt; 0.05; right ear: r = 0.367, p & lt; 0.001). Hearing threshold elevations, especially in high frequency, might explain the appearance of dominant high-frequency TP in patients without clinically defined hearing loss. This is consistent with the causal role of high-frequency coding in the generation of tinnitus.
    Type of Medium: Online Resource
    ISSN: 1662-5102
    URL: Article
    DOI: 10.3389/fncel.2022.804745
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2452963-1
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