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  1. Article ; Online: Cryo-EM of the Nucleosome Core Particle Bound to Ran-RCC1 Reveals a Dynamic Complex.

    Huang, Shuya Kate / Rubinstein, John L / Kay, Lewis E

    Biochemistry

    2024  Volume 63, Issue 7, Page(s) 880–892

    Abstract: Ras-related nuclear protein (Ran) is a member of the Ras superfamily of small guanosine triphosphatases (GTPases) and a regulator of multiple cellular processes. In healthy cells, the GTP-bound form of Ran is concentrated at chromatin, creating a Ran•GTP ...

    Abstract Ras-related nuclear protein (Ran) is a member of the Ras superfamily of small guanosine triphosphatases (GTPases) and a regulator of multiple cellular processes. In healthy cells, the GTP-bound form of Ran is concentrated at chromatin, creating a Ran•GTP gradient that provides the driving force for nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation. The Ran•GTP gradient is maintained by the regulator of chromatin condensation 1 (RCC1), a guanine nucleotide exchange factor that accelerates GDP/GTP exchange in Ran. RCC1 interacts with nucleosomes, which are the fundamental repeating units of eukaryotic chromatin. Here, we present a cryo-EM analysis of a trimeric complex composed of the nucleosome core particle (NCP), RCC1, and Ran. While the contacts between RCC1 and Ran in the complex are preserved compared with a previously determined structure of RCC1-Ran, our study reveals that RCC1 and Ran interact dynamically with the NCP and undergo rocking motions on the nucleosome surface. Furthermore, the switch 1 region of Ran, which plays an important role in mediating conformational changes associated with the substitution of GDP and GTP nucleotides in Ras family members, appears to undergo disorder-order transitions and forms transient contacts with the C-terminal helix of histone H2B. Nucleotide exchange assays performed in the presence and absence of NCPs are not consistent with an active role for nucleosomes in nucleotide exchange, at least
    MeSH term(s) Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/metabolism ; Chromatin ; Cryoelectron Microscopy ; Guanosine Triphosphate/metabolism ; Nuclear Proteins/chemistry ; Nuclear Proteins/metabolism ; Nucleosomes/chemistry ; Nucleosomes/metabolism ; Nucleotides/metabolism ; ran GTP-Binding Protein/metabolism ; Humans ; Guanine Nucleotide Exchange Factors/chemistry ; Guanine Nucleotide Exchange Factors/metabolism
    Chemical Substances Cell Cycle Proteins ; Chromatin ; Guanosine Triphosphate (86-01-1) ; Nuclear Proteins ; Nucleosomes ; Nucleotides ; ran GTP-Binding Protein (EC 3.6.5.2) ; RCC1 protein, human ; Guanine Nucleotide Exchange Factors
    Language English
    Publishing date 2024-03-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/acs.biochem.3c00724
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Dynamics and mechanistic underpinnings to pharmacology of class A GPCRs: an NMR perspective.

    Huang, Shuya Kate / Prosser, R Scott

    American journal of physiology. Cell physiology

    2022  Volume 322, Issue 4, Page(s) C739–C753

    Abstract: One-third of current pharmaceuticals target G protein-coupled receptors (GPCRs), the largest receptor superfamily in humans and mediators of diverse physiological processes. This review summarizes the recent progress in GPCR structural dynamics, focusing ...

    Abstract One-third of current pharmaceuticals target G protein-coupled receptors (GPCRs), the largest receptor superfamily in humans and mediators of diverse physiological processes. This review summarizes the recent progress in GPCR structural dynamics, focusing on class A receptors and insights derived from nuclear magnetic resonance (NMR) and other spectroscopic techniques. We describe the structural aspects of GPCR activation and the various pharmacological models that capture aspects of receptor signaling behavior. Spectroscopic studies revealed that receptors and their signaling complexes are dynamic allosteric systems that sample multiple functional states under basal conditions. The distribution of states within the conformational ensemble and the kinetics of transitions between states are regulated through the binding of ligands, allosteric modulators, and the membrane environment. This ensemble view of GPCRs provides a mechanistic framework for understanding many of the pharmacological phenomena associated with receptor signaling, such as basal activity, efficacy, and functional bias.
    MeSH term(s) Humans ; Ligands ; Magnetic Resonance Spectroscopy ; Protein Conformation ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction
    Chemical Substances Ligands ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00044.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Smart Nanocarriers for the Treatment of Retinal Diseases.

    Liu, Shuya / Yan, Zhike / Huang, Zixiang / Yang, Huanghao / Li, Jingying

    ACS applied bio materials

    2024  Volume 7, Issue 4, Page(s) 2070–2085

    Abstract: Retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and retinoblastoma, stand as the leading causes of irreversible vision impairment and blindness worldwide. Effectively administering drugs for retinal diseases poses a ... ...

    Abstract Retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and retinoblastoma, stand as the leading causes of irreversible vision impairment and blindness worldwide. Effectively administering drugs for retinal diseases poses a formidable challenge due to the presence of complex ocular barriers and elimination mechanisms. Over time, various approaches have been developed to fabricate drug delivery systems for improving retinal therapy including virus vectors, lipid nanoparticles, and polymers. However, conventional nanocarriers encounter issues related to the controllability, efficiency, and safety in the retina. Therefore, the development of smart nanocarriers for effective or more invasive long-term treatment remains a desirable goal. Recently, approaches have surfaced for the intelligent design of nanocarriers, leveraging specific responses to external or internal triggers and enabling multiple functions for retinal therapy such as topical administration, prolonged drug release, and site-specific drug delivery. This Review provides an overview of prevalent retinal pathologies and related pharmacotherapies to enhance the understanding of retinal diseases. It also surveys recent developments and strategies employed in the intelligent design of nanocarriers for retinal disease. Finally, the challenges of smart nanocarriers in potential clinical retinal therapeutic applications are discussed to inspire the next generation of smart nanocarriers.
    MeSH term(s) Humans ; Retinal Diseases/drug therapy ; Drug Delivery Systems ; Pharmaceutical Preparations
    Chemical Substances Pharmaceutical Preparations
    Language English
    Publishing date 2024-03-15
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.3c01289
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: NMR-Based Metabolic Profiling of the Effects of α-Ketoglutarate Supplementation on Energy-Deficient C2C12 Myotubes.

    Li, Yantong / Zhang, Shuya / Huang, Caihua / Lin, Donghai

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 9

    Abstract: Skeletal muscle is closely linked to energy metabolism, but it is inevitably deprived of energy. Cellular differentiation is an essential and energy-demanding process in skeletal muscle development. Much attention has been paid to identifying beneficial ... ...

    Abstract Skeletal muscle is closely linked to energy metabolism, but it is inevitably deprived of energy. Cellular differentiation is an essential and energy-demanding process in skeletal muscle development. Much attention has been paid to identifying beneficial factors that promote skeletal muscle satellite cell differentiation and further understanding the underlying regulatory mechanisms. As a critical metabolic substrate or regulator, α-ketoglutarate (AKG) has been recognized as a potential nutritional supplement or therapeutic target for skeletal muscle. We have previously found beneficial effects of AKG supplementation on the proliferation of C2C12 myoblasts cultured under both normal and energy-deficient conditions and have further elucidated the underlying metabolic mechanisms. However, it remains unclear what role AKG plays in myotube formation in different energy states. In the present study, we investigated the effects of AKG supplementation on the differentiation of C2C12 myoblasts cultured in normal medium (Nor myotubes) and low glucose medium (Low myotubes) and performed NMR-based metabonomic profiling to address AKG-induced metabolic changes in both Nor and Low myotubes. Significantly, AKG supplementation promoted myotube formation and induced metabolic remodeling in myotubes under normal medium and low glucose medium, including improved energy metabolism and enhanced antioxidant capacity. Specifically, AKG mainly altered amino acid metabolism and antioxidant metabolism and upregulated glycine levels and antioxidase expression. Our results are typical for the mechanistic understanding of the effects of AKG supplementation on myotube formation in the two energy states. This study may be beneficial for further exploring the applications of AKG supplementation in sports, exercise, and therapy.
    MeSH term(s) Antioxidants/metabolism ; Ketoglutaric Acids/pharmacology ; Ketoglutaric Acids/metabolism ; Muscle Fibers, Skeletal/metabolism ; Dietary Supplements ; Glucose
    Chemical Substances Antioxidants ; Ketoglutaric Acids ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-04-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28093840
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Metabolomic Analysis of Trehalose Alleviating Oxidative Stress in Myoblasts.

    Zhang, Shuya / Qiu, Xu / Zhang, Yue / Huang, Caihua / Lin, Donghai

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: Trehalose, a naturally occurring non-toxic disaccharide, has attracted considerable attention for its potential in alleviating oxidative stress in skeletal muscle. In this study, our aim was to elucidate the metabolic mechanisms underlying the protective ...

    Abstract Trehalose, a naturally occurring non-toxic disaccharide, has attracted considerable attention for its potential in alleviating oxidative stress in skeletal muscle. In this study, our aim was to elucidate the metabolic mechanisms underlying the protective effects of trehalose against hydrogen peroxide (H
    MeSH term(s) Trehalose/pharmacology ; Hydrogen Peroxide ; NF-E2-Related Factor 2 ; Metabolomics ; Oxidative Stress ; Myoblasts
    Chemical Substances Trehalose (B8WCK70T7I) ; Hydrogen Peroxide (BBX060AN9V) ; NF-E2-Related Factor 2
    Language English
    Publishing date 2023-08-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241713346
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Innovating management mechanism to promote the development of curriculum of ideological and political education penetrating into all majors of medical corses

    HUANG Fumin, HE Shuya, WANG Jing

    Jichu yixue yu linchuang, Vol 43, Iss 2, Pp 360-

    2023  Volume 362

    Abstract: Ideological and political education is a process in which teachers of specialized courses integrate ideological and political education into classroom teaching and reform while imparting professional knowledge. It is the due meaning of medical education ... ...

    Abstract Ideological and political education is a process in which teachers of specialized courses integrate ideological and political education into classroom teaching and reform while imparting professional knowledge. It is the due meaning of medical education and the inevitable pursuit of medical colleges to carry out the fundamental task of cultivating people by virtue. How to integrate the ideological and political education into the teaching of medical professional knowledge needs teachers to play a leading role and to innovate the current teaching management mechanism. From the perspective view point of administrators, this paper puts forward some suggestions on how to improve the management mechanism and promote the development of ideological and political curriculum penetrating into all medical course.
    Keywords management mechanism|medical college|ideological and political education through all majors ; Medicine ; R
    Language Chinese
    Publishing date 2023-02-01T00:00:00Z
    Publisher Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Increase the Power of Epigenome-Wide Association Testing Using ICC-Based Hypothesis Weighting.

    Cui, Bowen / Cui, Shuya / Huang, Jinyan / Chen, Jun

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2432, Page(s) 113–122

    Abstract: For large-scale hypothesis testing such as epigenome-wide association testing, adaptively focusing power on the more promising hypotheses can lead to a much more powerful multiple testing procedure. In this chapter, we introduce a multiple testing ... ...

    Abstract For large-scale hypothesis testing such as epigenome-wide association testing, adaptively focusing power on the more promising hypotheses can lead to a much more powerful multiple testing procedure. In this chapter, we introduce a multiple testing procedure that weights each hypothesis based on the intraclass correlation coefficient (ICC), a measure of "noisiness" of CpG methylation measurement, to increase the power of epigenome-wide association testing. Compared to the traditional multiple testing procedure on a filtered CpG set, the proposed procedure circumvents the difficulty to determine the optimal ICC cutoff value and is overall more powerful. We illustrate the procedure and compare the power to classical multiple testing procedures using an example data.
    MeSH term(s) Epigenome ; Research Design
    Language English
    Publishing date 2022-05-03
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1994-0_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Engaging Users on a Q&A Social Media Platform: The Influence of Disease Attributes and Message Features on Public Discussions of Depression.

    Pan, Shuya / Yu, Nan / Huang, Yao / Zhang, Di

    Frontiers in psychology

    2021  Volume 12, Page(s) 712346

    Language English
    Publishing date 2021-09-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2563826-9
    ISSN 1664-1078
    ISSN 1664-1078
    DOI 10.3389/fpsyg.2021.712346
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Natural Targeting Potent ROS-Eliminating Tungsten-Based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension.

    Liu, Hong / Wang, Shuya / Chen, Qiaohui / Ge, Xiaoyue / Ning, Huang / Guo, Yanzi / Wang, Di / Ai, Kelong / Hu, Changping

    Advanced healthcare materials

    2023  Volume 12, Issue 30, Page(s) e2303784

    Language English
    Publishing date 2023-12-04
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202303784
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  10. Article ; Online: Deciphering the dynamics and driving mechanisms of high-risk antibiotic resistome in size-fractionated bacterial community during drinking water chlorination via metagenomic analysis.

    Wang, Shuya / Zhuang, Yan / Gao, Linjun / Huang, Hongbin / Zhang, Xian / Jia, Shuyu / Shi, Peng / Zhang, Xu-Xiang

    Journal of hazardous materials

    2024  Volume 466, Page(s) 133572

    Abstract: To reveal the impact of chlorination on the high-risk resistome in size-fractionated bacterial community, we employed metagenomic approaches to decipher dynamics of high-risk antibiotic resistance genes (ARGs) and driving mechanisms in the free-living ... ...

    Abstract To reveal the impact of chlorination on the high-risk resistome in size-fractionated bacterial community, we employed metagenomic approaches to decipher dynamics of high-risk antibiotic resistance genes (ARGs) and driving mechanisms in the free-living and particle-associated fractions within a full-scale drinking water treatment system. Our results revealed that chlorination significantly increased the relative abundance of high-risk ARGs in the free-living fraction to 0.33 ± 0.005 copies/cell (cpc), bacitracin and chloramphenicol resistance types were major contributors. Furthermore, chlorination significantly increased the relative abundance of mobile genetic elements (MGEs) in the free-living fraction, while decreasing it in the particle-associated fraction. During chlorination, size-fractionated bacterial communities varied considerably. Multiple statistical analyses highlighted the pivotal role of the bacterial community in altering high-risk ARGs in both the free-living and particle-associated fractions, while MGEs had a more pronounced impact on high-risk ARGs in the free-living fraction. Specifically, the enrichment of pathogenic hosts, such as Comamonas and Pseudomonas, led to an increase in the abundance of high-risk ARGs. Concurrently, MGEs exhibited significant correlations with high-risk ARGs, indicating the potential of horizontal transfer of high-risk ARGs. These findings provide novel insights for mitigating antibiotic resistance risk by considering different bacterial fractions and respective risk ranks in drinking water.
    MeSH term(s) Drinking Water ; Anti-Bacterial Agents/pharmacology ; Halogenation ; Bacteria/genetics ; Drug Resistance, Microbial/genetics ; Genes, Bacterial
    Chemical Substances Drinking Water ; Anti-Bacterial Agents
    Language English
    Publishing date 2024-01-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1491302-1
    ISSN 1873-3336 ; 0304-3894
    ISSN (online) 1873-3336
    ISSN 0304-3894
    DOI 10.1016/j.jhazmat.2024.133572
    Database MEDical Literature Analysis and Retrieval System OnLINE

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