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  • Oxford University Press (OUP)  (29)
  • 2020-2024  (29)
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  • Oxford University Press (OUP)  (29)
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  • 2020-2024  (29)
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Subjects(RVK)
  • 1
    In: Brain Communications, Oxford University Press (OUP)
    Abstract: The structural network damages in amyotrophic lateral sclerosis patients are evident but contradictory due to the high heterogeneity of disease. We hypothesized that patterns of structural network impairments would be different in amyotrophic lateral sclerosis subtypes by a data-driven method using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) hybrid imaging. The data of PET, structural MRI and diffusion tensor imaging in fifty patients with amyotrophic lateral sclerosis and twenty-three healthy controls were collected by a 18F-FDG PET/MR hybrid. Two amyotrophic lateral sclerosis subtypes were identified as the optimal cluster based on gray matter volume and standardized uptake value ratio. Network metrics at the global, local and connection levels were compared to explore the impaired patterns of structural network in the identified subtypes. Compared with healthy controls, the two amyotrophic lateral sclerosis subtypes displayed a pattern of a locally impaired structural network centralized in the sensorimotor network and a pattern of an extensively impaired structural network in the whole brain. When comparing the two amyotrophic lateral sclerosis subgroups by a support vector machine classifier based on the decreases in nodal efficiency of structural network, the individualized network scores were obtained in every amyotrophic lateral sclerosis patient and demonstrated a positive correlation with disease severity. We clustered two amyotrophic lateral sclerosis subtypes by a data-driven method, which encompassed different patterns of structural network impairments. Our results imply that amyotrophic lateral sclerosis may possess the intrinsic damaged pattern of white matter network and thus provide a latent direction for stratification in clinical research.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 3020013-1
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Nucleic Acids Research Vol. 50, No. 17 ( 2022-09-23), p. 9858-9872
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 50, No. 17 ( 2022-09-23), p. 9858-9872
    Abstract: RNA molecules harbor diverse modifications that play important regulatory roles in a variety of biological processes. Over 150 modifications have been identified in RNA molecules. N6-methyladenosine (m6A) and 1-methyladenosine (m1A) are prevalent modifications occurring in various RNA species of mammals. Apart from the single methylation of adenosine (m6A and m1A), dual methylation modification occurring in the nucleobase of adenosine, such as N6,N6-dimethyladenosine (m6,6A), also has been reported to be present in RNA of mammals. Whether there are other forms of dual methylation modification occurring in the nucleobase of adenosine other than m6,6A remains elusive. Here, we reported the existence of a novel adenosine dual methylation modification, i.e. 1,N6-dimethyladenosine (m1,6A), in tRNAs of living organisms. We confirmed that m1,6A is located at position 58 of tRNAs and is prevalent in mammalian cells and tissues. The measured level of m1,6A ranged from 0.0049% to 0.047% in tRNAs. Furthermore, we demonstrated that TRMT6/61A could catalyze the formation of m1,6A in tRNAs and m1,6A could be demethylated by ALKBH3. Collectively, the discovery of m1,6A expands the diversity of RNA modifications and may elicit a new tRNA modification-mediated gene regulation pathway.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 3
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), ( 2022-12-22)
    Abstract: Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. Methods Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan–Meier method and Cox proportional hazards models. Results A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4–13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. Conclusions The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1465709-0
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  • 4
    In: Stem Cells Translational Medicine, Oxford University Press (OUP), Vol. 9, No. 2 ( 2020-02-01), p. 273-283
    Abstract: Chondrocyte hypertrophy-like change is an important pathological process of osteoarthritis (OA), but the mechanism remains largely unknown. Neural cell adhesion molecule (NCAM) is highly expressed and involved in the chondrocyte differentiation of mesenchymal stem cells (MSCs). In this study, we found that NCAM deficiency accelerates chondrocyte hypertrophy in articular cartilage and growth plate of OA mice. NCAM deficiency leads to hypertrophic chondrocyte differentiation in both murine MSCs and chondrogenic cells, in which extracellular signal-regulated kinase (ERK) signaling plays an important role. Moreover, NCAM expression is downregulated in an interleukin-1β-stimulated OA cellular model and monosodium iodoacetate-induced OA rats. Overexpression of NCAM substantially inhibits hypertrophic differentiation in the OA cellular model. In conclusion, NCAM could inhibit hypertrophic chondrocyte differentiation of MSCs by inhibiting ERK signaling and reduce chondrocyte hypertrophy in experimental OA model, suggesting the potential utility of NCAM as a novel therapeutic target for alleviating chondrocyte hypertrophy of OA. Significance statement Defects in the cartilage are irreversible and difficult to repair in osteoarthritis (OA) patients. A cell-based therapeutic approach for cartilage regeneration using mesenchymal stem cells (MSCs) has gained attention in recent years; however, chondrogenic differentiation of MSCs is usually inefficient because of excessive chondrocyte hypertrophy-like change under inflammatory intra-articular conditions caused by OA. The present study provides the first experimental evidence for neural cell adhesion molecule (NCAM) on the cartilage repair of OA treatment. It has been demonstrated that NCAM deficiency enhances chondrocyte hypertrophy in chondrogenic differentiation of MSCs and in experimental OA, and upregulation of NCAM inhibits hypertrophic chondrocyte differentiation. The results suggest a more efficient strategy for the cartilage repair of OA treatment using NCAM-overexpressing MSCs.
    Type of Medium: Online Resource
    ISSN: 2157-6564 , 2157-6580
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2642270-0
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  • 5
    In: The Oncologist, Oxford University Press (OUP), Vol. 26, No. 8 ( 2021-08-01), p. e1320-e1326
    Abstract: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed. Methods This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti–epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti–vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80–120 mg per day for 14 days), and raltitrexed (3 mg/m2 on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0–155.0) and 367 days (95% CI, 310.4–423.6), respectively. The combination was well tolerated. Conclusion Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2023829-0
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  • 6
    In: QJM: An International Journal of Medicine, Oxford University Press (OUP), ( 2023-10-06)
    Abstract: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. Aim To investigate the association between specific environmental factors and the generalization of OMG. Design The cohort study was conducted in China based on a nationwide multicenter database. Methods Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. Results A total of 1396 participants were included. During a median follow-up of 5.15 (IQR 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity & lt;0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. Conclusions Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.
    Type of Medium: Online Resource
    ISSN: 1460-2725 , 1460-2393
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1492613-1
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  • 7
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 51, No. D1 ( 2023-01-06), p. D488-D508
    Abstract: The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), founding member of the Worldwide Protein Data Bank (wwPDB), is the US data center for the open-access PDB archive. As wwPDB-designated Archive Keeper, RCSB PDB is also responsible for PDB data security. Annually, RCSB PDB serves  & gt;10 000 depositors of three-dimensional (3D) biostructures working on all permanently inhabited continents. RCSB PDB delivers data from its research-focused RCSB.org web portal to many millions of PDB data consumers based in virtually every United Nations-recognized country, territory, etc. This Database Issue contribution describes upgrades to the research-focused RCSB.org web portal that created a one-stop-shop for open access to ∼200 000 experimentally-determined PDB structures of biological macromolecules alongside  & gt;1 000 000 incorporated Computed Structure Models (CSMs) predicted using artificial intelligence/machine learning methods. RCSB.org is a ‘living data resource.’ Every PDB structure and CSM is integrated weekly with related functional annotations from external biodata resources, providing up-to-date information for the entire corpus of 3D biostructure data freely available from RCSB.org with no usage limitations. Within RCSB.org, PDB structures and the CSMs are clearly identified as to their provenance and reliability. Both are fully searchable, and can be analyzed and visualized using the full complement of RCSB.org web portal capabilities.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Nucleic Acids Research Vol. 48, No. 17 ( 2020-09-25), p. 9747-9761
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 48, No. 17 ( 2020-09-25), p. 9747-9761
    Abstract: Kinetoplastid flagellates are known for several unusual features, one of which is their complex mitochondrial genome, known as kinetoplast (k) DNA, composed of mutually catenated maxi- and minicircles. Trypanosoma lewisi is a member of the Stercorarian group of trypanosomes which is, based on human infections and experimental data, now considered a zoonotic pathogen. By assembling a total of 58 minicircle classes, which fall into two distinct categories, we describe a novel type of kDNA organization in T. lewisi. RNA-seq approaches allowed us to map the details of uridine insertion and deletion editing events upon the kDNA transcriptome. Moreover, sequencing of small RNA molecules enabled the identification of 169 unique guide (g) RNA genes, with two differently organized minicircle categories both encoding essential gRNAs. The unprecedented organization of minicircles and gRNAs in T. lewisi broadens our knowledge of the structure and expression of the mitochondrial genomes of these human and animal pathogens. Finally, a scenario describing the evolution of minicircles is presented.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 9
    In: Database, Oxford University Press (OUP), Vol. 2022 ( 2022-11-24)
    Abstract: Drug–target association plays an important role in drug discovery, drug repositioning, drug synergy prediction, etc. Currently, a lot of drug-related databases, such as DrugBank and BindingDB, have emerged. However, these databases are separate, incomplete and non-uniform with different criteria. Here, we integrated eight drug-related databases; collected, filtered and supplemented drugs, target genes and experimentally validated (highly confident) associations and built a highly confident drug–target (HCDT: http://hainmu-biobigdata.com/hcdt) database. HCDT database includes 500 681 HCDT associations between 299 458 drugs and 5618 target genes. Compared to individual databases, HCDT database contains 1.1 to 254.2 times drugs, 1.8–5.5 times target genes and 1.4–27.7 times drug–target associations. It is normative, publicly available and easy for searching, browsing and downloading. Together with multi-omics data, it will be a good resource in analyzing the drug functional mechanism, mining drug-related biological pathways, predicting drug synergy, etc. Database URL: http://hainmu-biobigdata.com/hcdt
    Type of Medium: Online Resource
    ISSN: 1758-0463
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2496706-3
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  • 10
    In: Protein & Cell, Oxford University Press (OUP), Vol. 13, No. 7 ( 2022-07), p. 490-512
    Abstract: LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28’s role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux . LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
    Type of Medium: Online Resource
    ISSN: 1674-8018
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2543451-2
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