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  1. Article ; Online: Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood mononuclear cells after chemotherapy.

    Hu, Xuqiao / Cao, Dongyan / Zhou, Zhenru / Wang, Zhaoyang / Zeng, Jieying / Hong, Wen-Xu

    Cellular oncology (Dordrecht)

    2023  Volume 47, Issue 1, Page(s) 97–112

    Abstract: Purpose: Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells residing in a complex microenvironment. However, the immune cell types, status, and ... ...

    Abstract Purpose: Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells residing in a complex microenvironment. However, the immune cell types, status, and genome profile of the peripheral blood mononuclear cell (PBMC) microenvironment in AML patients after chemotherapy are poorly understood. In order to explore the immune microenvironment of AML patients after chemotherapy, we conducted this study for providing insights into precision medicine and immunotherapy of AML.
    Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) to analyse the PBMC microenvironment from five AML patients treated with different chemotherapy regimens and six healthy donors. We compared the cell compositions in AML patients and healthy donors, and performed gene set enrichment analysis (GSEA), CellPhoneDB, and copy number variation (CNV) analysis.
    Results: Using scRNA-seq technology, 91,772 high quality cells of 44,950 PBMCs from AML patients and 46,822 PBMCs from healthy donors were classified as 14 major cell clusters. Our study revealed the sub-cluster diversity of T cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), and haematopoietic stem cell progenitors (HSC-Prog) in AML patients under chemotherapy. NK cells and monocyte-DCs showed significant changes in transcription factor expression and chromosome copy number variation (CNV). We also observed significant heterogeneity in CNV and intercellular interaction networks in HSC-Prog cells.
    Conclusion: Our results elucidated the PBMC single-cell landscape and provided insights into precision medicine and immunotherapy for treating AML.
    MeSH term(s) Humans ; Leukocytes, Mononuclear ; DNA Copy Number Variations ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; T-Lymphocytes ; Gene Expression Profiling ; Tumor Microenvironment
    Language English
    Publishing date 2023-08-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2595109-9
    ISSN 2211-3436 ; 1875-8606 ; 2211-3428
    ISSN (online) 2211-3436
    ISSN 1875-8606 ; 2211-3428
    DOI 10.1007/s13402-023-00853-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6908: Show issues Location:
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  2. Article ; Online: Gold drugs as colistin adjuvants in the fight against MCR-1 producing bacteria.

    Zhang, Qi / Wang, Minji / Hu, Xuqiao / Yan, Aixin / Ho, Pak-Leung / Li, Hongyan / Sun, Hongzhe

    Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry

    2023  Volume 28, Issue 2, Page(s) 225–234

    Abstract: The emergence and rapid spread of the mobile colistin resistance gene mcr-1 among bacterial species and hosts significantly challenge the efficacy of "last-line" antibiotic colistin. Previously, we reported silver nitrate and auranofin serve as colistin ... ...

    Abstract The emergence and rapid spread of the mobile colistin resistance gene mcr-1 among bacterial species and hosts significantly challenge the efficacy of "last-line" antibiotic colistin. Previously, we reported silver nitrate and auranofin serve as colistin adjuvants for combating mcr-1-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing mcr-1-positive bacteria. However, pre-activation of the drugs by either glutathione or N-acetyl cysteine, thus releasing and accumulating gold ions, is perquisite for their abilities to substitute zinc cofactor from MCR-1 enzyme. X-ray crystallography and biophysical studies further supported the proposed mechanism. This study not only provides basis for combining gold-based drugs and colistin for combating mcr-1-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance.
    MeSH term(s) Colistin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Bacteria ; Gold/pharmacology ; Drug Resistance, Bacterial/genetics ; Plasmids ; Escherichia coli Proteins/chemistry ; Microbial Sensitivity Tests
    Chemical Substances Colistin (Z67X93HJG1) ; Anti-Bacterial Agents ; Gold (7440-57-5) ; Escherichia coli Proteins
    Language English
    Publishing date 2023-01-20
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1464026-0
    ISSN 1432-1327 ; 0949-8257
    ISSN (online) 1432-1327
    ISSN 0949-8257
    DOI 10.1007/s00775-022-01983-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Knockdown of ARL5B Induces Mitochondrial-mediated Apoptosis and Inhibits Glycolysis in Breast Cancer Cells by Activating MDA5 Signaling.

    Zhang, Lei / Hu, Xuqiao / Wu, Huaiyu / Tian, Hongtian / Zeng, Jieying / Song, Di / Yang, Keen / Chen, Jing / Xu, Jinfeng / Dong, Fajin

    Current cancer drug targets

    2022  Volume 22, Issue 10, Page(s) 843–853

    Abstract: Aim: Mitochondria are essential for energy metabolism in the tumor microenvironment and the survival of cancer cells.: Background: ADP-ribosylation factor-like GTPase 5b (ARL5B) has been found to be associated with mitochondrial dysfunction and ... ...

    Abstract Aim: Mitochondria are essential for energy metabolism in the tumor microenvironment and the survival of cancer cells.
    Background: ADP-ribosylation factor-like GTPase 5b (ARL5B) has been found to be associated with mitochondrial dysfunction and breast cancer (BC) progression, but the underlying mechanism needs to be further understood.
    Objective: We investigated the effects of ARL5B on the apoptosis and glycolysis of breast cancer cells and its underlying mechanisms.
    Methods: Quantitative reverse transcription-PCR (qRT-PCR) and western blot assays were used to detect the expression of ARL5B in breast cancer tissues and cells. An ARL5B loss-of-function assay was performed to verify its role in BC development.
    Results: ARL5B was upregulated in breast cancer tissues and cell lines. ARL5B knockdown induced apoptosis and activated the mitochondrial pathway in breast cancer cells. Interestingly, the inhibition of ARL5B repressed the aerobic glycolysis of breast cancer cells. The role of ARL5B in breast cancer cells was exerted by mediating the activation of viral RNA sensor MDA5-evoked signaling. Silencing ARL5B triggered MDA5 signaling by upregulating the key proteins involved in the MDA5 pathway. Importantly, MDA5 silencing reversed the effects of ARL5B knockdown on mitochondrial-mediated apoptosis and glycolysis, whereas poly (I:C), as a ligand for MDA5, further enhanced ARL5B knockdown- facilitated mitochondrial apoptosis and the inhibition of glycolysis.
    Conclusion: The knockdown of ARL5B activated MDA5 signaling and thus led to the enhanced mitochondrial- mediated apoptosis and glycolysis inhibition in breast cancer cells. Our study suggested that ARL5B might be a potential therapy target for BC.
    MeSH term(s) ADP-Ribosylation Factors/genetics ; ADP-Ribosylation Factors/metabolism ; ADP-Ribosylation Factors/pharmacology ; Apoptosis ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Female ; Glycolysis ; Humans ; Ligands ; Mitochondria ; RNA, Viral ; Tumor Microenvironment
    Chemical Substances Ligands ; RNA, Viral ; ARL5B protein, human (EC 3.6.1.2) ; ADP-Ribosylation Factors (EC 3.6.5.2)
    Language English
    Publishing date 2022-05-12
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2064824-8
    ISSN 1873-5576 ; 1568-0096
    ISSN (online) 1873-5576
    ISSN 1568-0096
    DOI 10.2174/1568009622666220511112538
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5589: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  4. Article: The study of antiviral drugs targeting SARS-CoV-2 nucleocapsid and spike proteins through large-scale compound repurposing.

    Hu, Xuqiao / Zhou, Zhenru / Li, Fei / Xiao, Yang / Wang, Zhaoyang / Xu, Jinfeng / Dong, Fajin / Zheng, Hairong / Yu, Rongmin

    Heliyon

    2021  Volume 7, Issue 3, Page(s) e06387

    Abstract: Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors ... ...

    Abstract Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors targeting nucleocapsid protein (N) and spike protein (S) of SARS-CoV-2. 16 screened candidates with higher binding affinity are evaluated via virtual screening. Comparing to those under trial/temporarily used antivirus drugs (i.e., umifenovir, lopinavir), ceftriaxone, cefotaxime, and cefuroxime show higher binding affinities to the N-terminal domain of N protein (N-NTD), C-terminal domain of N protein (N-CTD), and receptor-binding domain of S protein (S-RBD). Cefotaxime and cefuroxime have high binding affinities towards S-RBD with angiotensin-converting enzyme 2 (ACE2) complex via influence the critical interface sites at the interface of S-RBD (Arg
    Language English
    Publishing date 2021-03-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2021.e06387
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The study of antiviral drugs targeting SARS-CoV-2 nucleocapsid and spike proteins through large-scale compound repurposing

    Xuqiao Hu / Zhenru Zhou / Fei Li / Yang Xiao / Zhaoyang Wang / Jinfeng Xu / Fajin Dong / Hairong Zheng / Rongmin Yu

    Heliyon, Vol 7, Iss 3, Pp e06387- (2021)

    2021  

    Abstract: Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors ... ...

    Abstract Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors targeting nucleocapsid protein (N) and spike protein (S) of SARS-CoV-2.16 screened candidates with higher binding affinity are evaluated via virtual screening. Comparing to those under trial/temporarily used antivirus drugs (i.e., umifenovir, lopinavir), ceftriaxone, cefotaxime, and cefuroxime show higher binding affinities to the N-terminal domain of N protein (N-NTD), C-terminal domain of N protein (N-CTD), and receptor-binding domain of S protein (S-RBD). Cefotaxime and cefuroxime have high binding affinities towards S-RBD with angiotensin-converting enzyme 2 (ACE2) complex via influence the critical interface sites at the interface of S-RBD (Arg403, Tyr453, Trp495, Gly496, Phe497, Asn501and Tyr505) and ACE2 (Asn33, His34, Glu37, Asp38, Lys353, Ala386, Ala387, Gln388, Pro389, Phe390 and Arg393) complex.
    Keywords SARS-CoV-2 ; Drug screen and repurposing ; Small molecule microarray chip ; Antiviral compounds ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: One step further into the blackbox: a pilot study of how to build more confidence around an AI-based decision system of breast nodule assessment in 2D ultrasound.

    Dong, Fajin / She, Ruilian / Cui, Chen / Shi, Siyuan / Hu, Xuqiao / Zeng, Jieying / Wu, Huaiyu / Xu, Jinfeng / Zhang, Yun

    European radiology

    2021  Volume 31, Issue 7, Page(s) 4991–5000

    Abstract: Objectives: To investigate how a DL model makes decisions in lesion classification with a newly defined region of evidence (ROE) by incorporating "explainable AI" (xAI) techniques.: Methods: A data set of 785 2D breast ultrasound images acquired from ...

    Abstract Objectives: To investigate how a DL model makes decisions in lesion classification with a newly defined region of evidence (ROE) by incorporating "explainable AI" (xAI) techniques.
    Methods: A data set of 785 2D breast ultrasound images acquired from 367 females. The DenseNet-121 was used to classify whether the lesion is benign or malignant. For performance assessment, classification results are evaluated by calculating accuracy, sensitivity, specificity, and receiver operating characteristic for experiments of both coarse and fine regions of interest (ROIs). The area under the curve (AUC) was evaluated, and the true-positive, false-positive, true-negative, and false-negative results with breakdown in high, medium, and low resemblance on test sets were also reported.
    Results: The two models with coarse and fine ROIs of ultrasound images as input achieve an AUC of 0.899 and 0.869, respectively. The accuracy, sensitivity, and specificity of the model with coarse ROIs are 88.4%, 87.9%, and 89.2%, and with fine ROIs are 86.1%, 87.9%, and 83.8%, respectively. The DL model captures ROE with high resemblance of physicians' consideration as they assess the image.
    Conclusions: We have demonstrated the effectiveness of using DenseNet to classify breast lesions with limited quantity of 2D grayscale ultrasound image data. We have also proposed a new ROE-based metric system that can help physicians and patients better understand how AI makes decisions in reading images, which can potentially be integrated as a part of evidence in early screening or triaging of patients undergoing breast ultrasound examinations.
    Key points: • The two models with coarse and fine ROIs of ultrasound images as input achieve an AUC of 0.899 and 0.869, respectively. The accuracy, sensitivity, and specificity of the model with coarse ROIs are 88.4%, 87.9%, and 89.2%, and with fine ROIs are 86.1%, 87.9%, and 83.8%, respectively. • The first model with coarse ROIs is slightly better than the second model with fine ROIs according to these evaluation metrics. • The results from coarse ROI and fine ROI are consistent and the peripheral tissue is also an impact factor in breast lesion classification.
    MeSH term(s) Artificial Intelligence ; Breast/diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Pilot Projects ; Sensitivity and Specificity ; Ultrasonography
    Language English
    Publishing date 2021-01-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1085366-2
    ISSN 1432-1084 ; 0938-7994 ; 1613-3749
    ISSN (online) 1432-1084
    ISSN 0938-7994 ; 1613-3749
    DOI 10.1007/s00330-020-07561-7
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3300: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice

    Xuqiao Hu / Fei Li / Jieying Zeng / Zhenru Zhou / Zhaoyang Wang / Jing Chen / Dongyan Cao / Yifan Hong / Laixin Huang / Yongsheng Chen / Jinfeng Xu / Fajin Dong / Rongmin Yu / Hairong Zheng

    Research, Vol

    2022  Volume 2022

    Abstract: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic and progressive inflammation of the synovium. Focused ultrasound therapy is an increasingly attractive alternative for treating RA owing to its noninvasiveness; however, it ...

    Abstract Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic and progressive inflammation of the synovium. Focused ultrasound therapy is an increasingly attractive alternative for treating RA owing to its noninvasiveness; however, it remains unclear which immune subsets respond to ultrasound stimulation. In this study, we showed that spleen-targeted low-frequency pulsed focused ultrasound (LFPFU) effectively improved the severity of arthritis in an arthritis mouse model established in DBA/1J mice. Additionally, we performed in-depth immune profiling of spleen samples from RA mice, RA mice that underwent ultrasound therapy, and healthy controls using mass cytometry along with extensive antibody panels and identified the immune composition of 14 cell populations, including CD4+/CD8+ T cells, B cells, natural killer cells, and dendritic cells. Moreover, multidimensional analysis according to cell-surface markers and phenotypes helped in identifying 4 and 5 cell subpopulations among T and myeloid cells, respectively, with 6 T cell subsets and 3 myeloid cell subsets responsive to ultrasound therapy among the 3 groups. Of these cell subsets, CD8+ T cell subsets showed a unique response to ultrasound stimulation in RA mice. Specifically, CD8+ T cells show a noticeable correlation with the degree of arthritis progression and could serve as an indicator for spleen-focused ultrasound-based therapy. Furthermore, single-cell RNA sequencing of spleen cells revealed the importance of T, B, and myeloid cell populations in the anti-inflammatory pathway. These results elucidated the unique cell subsets and transcriptome of splenic cells responsive to LFPFU and demonstrated the potential of spleen-focused ultrasound stimulation in the treatment of inflammatory diseases.
    Keywords Science ; Q
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher American Association for the Advancement of Science
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: S-Dimethylarsino-glutathione (darinaparsin®) targets histone H3.3, leading to TRAIL-induced apoptosis in leukemia cells

    Xu, Xiaohan / Wang, Haibo / Li, Hongyan / Hu, Xuqiao / Zhang, Yu / Guan, Xinyuan / Toy, Patrick H / Sun, Hongzhe

    Chemical communications. 2019 Oct. 29, v. 55, no. 87

    2019  

    Abstract: Histone H3.3 was identified as an arsenic-binding protein of S-dimethylarsino-glutathione (ZIO-101, darinaparsin®) in leukemia cells by GE-ICP-MS. Such a binding results in TRAIL-induced apoptosis. We further validate histone H3.3 as a vital target for ... ...

    Abstract Histone H3.3 was identified as an arsenic-binding protein of S-dimethylarsino-glutathione (ZIO-101, darinaparsin®) in leukemia cells by GE-ICP-MS. Such a binding results in TRAIL-induced apoptosis. We further validate histone H3.3 as a vital target for ZIO-101, offering new information on the mode of action of arsenic-based anticancer agents.
    Keywords antineoplastic agents ; apoptosis ; chemical compounds ; chemical reactions ; histones ; mechanism of action ; neoplasm cells
    Language English
    Dates of publication 2019-1029
    Size p. 13120-13123.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/c9cc07605k
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Multi-omics and temporal dynamics profiling reveal disruption of central metabolism in

    Han, Bingjie / Zhang, Zhen / Xie, Yanxuan / Hu, Xuqiao / Wang, Haibo / Xia, Wei / Wang, Yulan / Li, Hongyan / Wang, Yuchuan / Sun, Hongzhe

    Chemical science

    2018  Volume 9, Issue 38, Page(s) 7488–7497

    Abstract: Integration of multi-omics enables uncovering cellular responses to stimuli or the mechanism of action of a drug at a system level. Bismuth drugs have long been used for the treatment ... ...

    Abstract Integration of multi-omics enables uncovering cellular responses to stimuli or the mechanism of action of a drug at a system level. Bismuth drugs have long been used for the treatment of
    Language English
    Publishing date 2018-07-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2559110-1
    ISSN 2041-6539 ; 2041-6520
    ISSN (online) 2041-6539
    ISSN 2041-6520
    DOI 10.1039/c8sc01668b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Arsenic trioxide targets Hsp60, triggering degradation of p53 and survivin.

    Hu, Xuqiao / Li, Hongyan / Ip, Tiffany Ka-Yan / Cheung, Yam Fung / Koohi-Moghadam, Mohamad / Wang, Haibo / Yang, Xinming / Tritton, Daniel N / Wang, Yuchuan / Wang, Yi / Wang, Runming / Ng, Kwan-Ming / Naranmandura, Hua / Tse, Eric Wai-Choi / Sun, Hongzhe

    Chemical science

    2021  Volume 12, Issue 32, Page(s) 10893–10900

    Abstract: The mechanisms of action of arsenic trioxide (ATO), a clinically used drug for the treatment of acute promyelocytic leukemia (APL), have been actively studied mainly through characterization of individual putative protein targets. There appear to be no ... ...

    Abstract The mechanisms of action of arsenic trioxide (ATO), a clinically used drug for the treatment of acute promyelocytic leukemia (APL), have been actively studied mainly through characterization of individual putative protein targets. There appear to be no studies at a system level. Herein, we integrate metalloproteomics through a newly developed organoarsenic probe, As-AC (C
    Language English
    Publishing date 2021-07-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2559110-1
    ISSN 2041-6539 ; 2041-6520
    ISSN (online) 2041-6539
    ISSN 2041-6520
    DOI 10.1039/d1sc03119h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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