47 results on '"Minghui He"'
Search Results
2. Taxonomic and phylogenetic characterisations of six species of Pleosporales (in Didymosphaeriaceae, Roussoellaceae and Nigrogranaceae) from China
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Hongmin Hu, Minghui He, Youpeng Wu, Sihan Long, Xu Zhang, Lili Liu, Xiangchun Shen, Nalin N. Wijayawardene, Zebin Meng, Qingde Long, Jichuan Kang, and Qirui Li
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Botany ,QK1-989 - Abstract
Pleosporales comprise a diverse group of fungi with a global distribution and significant ecological importance. A survey on Pleosporales (in Didymosphaeriaceae, Roussoellaceae and Nigrogranaceae) in Guizhou Province, China, was conducted. Specimens were identified, based on morphological characteristics and phylogenetic analyses using a dataset composed of ITS, LSU, SSU, tef1 and rpb2 loci. Maximum Likelihood (ML) and Bayesian analyses were performed. As a result, three new species (Neokalmusia karka, Nigrograna schinifolium and N. trachycarpus) have been discovered, along with two new records for China (Roussoella neopustulans and R. doimaesalongensis) and a known species (Roussoella pseudohysterioides). Morphologically similar species and phylogenetically close taxa are compared and discussed. This study provides detailed information and descriptions of all newly-identified taxa.
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- 2023
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3. Advances in Research on Bacterial Oxidation of Mn(II): A Visualized Bibliometric Analysis Based on CiteSpace
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Wentao Mo, Hang Wang, Jianghan Wang, Yue Wang, Yunfei Liu, Yi Luo, Minghui He, Shuang Cheng, Huiting Mei, Jin He, and Jianmei Su
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Mn(II) oxidation ,manganese oxides ,Mn(II)-oxidizing bacteria ,CiteSpace ,bibliometric analysis ,visualized knowledge map ,Biology (General) ,QH301-705.5 - Abstract
Manganese (Mn) pollution poses a serious threat to the health of animals, plants, and humans. The microbial-mediated Mn(II) removal method has received widespread attention because of its rapid growth, high efficiency, and economy. Mn(II)-oxidizing bacteria can oxidize toxic soluble Mn(II) into non-toxic Mn(III/IV) oxides, which can further participate in the transformation of other heavy metals and organic pollutants, playing a crucial role in environmental remediation. This study aims to conduct a bibliometric analysis of research papers on bacterial Mn(II) oxidation using CiteSpace, and to explore the research hotspots and developmental trends within this field between 2008 and 2023. A series of visualized knowledge map analyses were conducted with 469 screened SCI research papers regarding annual publication quantity, author groups and their countries and regions, journal categories, publishing institutions, and keywords. China, the USA, and Japan published the most significant number of research papers on the research of bacterial Mn(II) oxidation. Research hotspots of bacterial Mn(II) oxidation mainly focused on the species and distributions of Mn(II)-oxidizing bacteria, the influencing factors of Mn(II) oxidation, the mechanisms of Mn(II) oxidation, and their applications in environment. This bibliometric analysis provides a comprehensive visualized knowledge map to quickly understand the current advancements, research hotspots, and academic frontiers in bacterial Mn(II) oxidation.
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- 2024
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4. Decoding the metabolomic responses of Caragana tibetica to livestock grazing in fragile ecosystems
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Minghui He, Yanlong Han, Yong Gao, Min Han, and Liqing Duan
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Caragana tibetica ,grazing intensity ,non-volatile metabolites ,regeneration ,stress response ,Plant culture ,SB1-1110 - Abstract
The population of Caragana tibetica, situated on the edge of the typical grassland-to-desert transition in the Mu Us Sandy Land, plays a vital ecological role in maintaining stability within the regional fragile ecosystem. Despite the consistent growth of C. tibetica following animal grazing, the biological mechanisms underlying its compensatory growth in response to livestock consumption remain unclear. Analyzing 48 metabolomic profiles from C. tibetica, our study reveals that the grazing process induces significant changes in the metabolic pathways of C. tibetica branches. Differential metabolites show correlations with soluble protein content, catalase, peroxidase, superoxide dismutase, malondialdehyde, and proline levels. Moreover, machine learning models built on these differential metabolites accurately predict the intensity of C. tibetica grazing (with an accuracy of 83.3%). The content of various metabolites, indicative of plant stress responses, including Enterolactone, Narceine, and Folcepri, exhibits significant variations in response to varying grazing intensities (P
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- 2024
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5. Analysis of Lake Area Dynamics and Driving Forces in the Jianghan Plain Based on GEE and SEM for the Period 1990 to 2020
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Minghui He and Yi Liu
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Jianghan Plain ,Google Earth Engine ,water body aera extraction ,PLS-SEM ,driving force analysis ,Science - Abstract
The lakes of Jianghan Plain, as an important component of the water bodies in the middle and lower reaches of the Yangtze River plain, have made significant contributions to maintaining the ecological health and promoting the sustainable development of the Jianghan Plain. However, there is a relatively limited understanding regarding the trends of lake area change for different types of lakes and their dominant factors over the past three decades in the Jianghan Plain. Based on the Google Earth Engine (GEE) platform, combined with the water body index method, the changes in area of three different types of lakes (area > 1 km2) in the Jianghan Lake Group from 1990 to 2020 were extracted and analyzed. Additionally, the Partial least squares structural equation model (PLS-SEM) was utilized to analyze the driving factors affecting the changes in water body area of these lakes. The results show that from 1990 to 2020, the area of the lakes of the wet season and level season exhibited a decreasing trend, decreasing by 893.1 km2 and 77.9 km2, respectively. However, the area of dry season lakes increased by 59.27 km2. The areas of all three types of lakes reached their minimum values in 2006. According to the PLS-SEM results, the continuous changes in the lakes’ area are mainly controlled by environmental factors overall. Furthermore, human factors mainly influence the mutation of the lakes’ area. This study achieved precise extraction of water body areas and accurate analysis of driving factors, providing a basis for a comprehensive understanding of the dynamic changes in the lakes of Jianghan Plain, which is beneficial for the rational utilization and protection of water resources.
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- 2024
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6. PtoMYB031, the R2R3 MYB transcription factor involved in secondary cell wall biosynthesis in poplar
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Feng Tang, Bo Jiao, Meng Zhang, Minghui He, Ruiying Su, Keming Luo, and Ting Lan
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secondary cell wall biosynthesis ,R2R3-MYB transcription factor ,PtoMYB031 ,transcriptional inhibition complex ,poplar ,Plant culture ,SB1-1110 - Abstract
IntroductionThe biosynthesis of the secondary cell wall (SCW) is orchestrated by an intricate hierarchical transcriptional regulatory network. This network is initiated by first-layer master switches, SCW-NAC transcription factors, which in turn activate the second-layer master switches MYBs. These switches play a crucial role in regulating xylem specification and differentiation during SCW formation. However, the roles of most MYBs in woody plants are yet to be fully understood.MethodsIn this study, we identified and isolated the R2R3-MYB transcription factor, PtoMYB031, from Populus tomentosa. We explored its expression, mainly in xylem tissues, and its role as a transcriptional repressor in the nucleus. We used overexpression and RNA interference techniques in poplar, along with Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays, to analyze the regulatory effects of PtoMYB031.ResultsOverexpression of PtoMYB031 in poplar significantly reduced lignin, cellulose, and hemicellulose content, and inhibited vascular development in stems, resulting in decreased SCW thickness in xylem tissues. Gene expression analysis showed that structural genes involved in SCW biosynthesis were downregulated in PtoMYB031-OE lines. Conversely, RNA interference of PtoMYB031 increased these compounds. Additionally, PtoMYB031 was found to recruit the repressor PtoZAT11, forming a transcriptional inhibition complex.DiscussionOur findings provide new insights into how PtoMYB031, through its interaction with PtoZAT11, forms a complex that can suppress the expression of key regulatory genes, PtoWND1A and PtoWND2B, in SCW biosynthesis. This study enhances our understanding of the transcriptional regulation involved in SCW formation in poplar, highlighting the significant role of PtoMYB031.
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- 2024
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7. Correction: Wu et al. Rust Fungi on Medicinal Plants in Guizhou Province with Descriptions of Three New Species. J. Fungi 2023, 9, 953
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Qianzhen Wu, Minghui He, Tiezhi Liu, Hongmin Hu, Lili Liu, Peng Zhao, and Qirui Li
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n/a ,Biology (General) ,QH301-705.5 - Abstract
Error in Figure [...]
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- 2023
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8. Rust Fungi on Medicinal Plants in Guizhou Province with Descriptions of Three New Species
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Qianzhen Wu, Minghui He, Tiezhi Liu, Hongmin Hu, Lili Liu, Peng Zhao, and Qirui Li
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medicinal plant ,molecular phylogeny ,new taxa ,phytopathogen ,Pucciniales ,Biology (General) ,QH301-705.5 - Abstract
During the research on rust fungi in medicinal plants of Guizhou Province, China, a total of 9 rust fungal species were introduced, including 3 new species (Hamaspora rubi-alceifolii, Nyssopsora altissima, and Phragmidium cymosum), as well as 6 known species (Melampsora laricis-populina, Melampsoridium carpini, Neophysopella ampelopsidis, Nyssopsora koelrezidis, P. rosae-roxburghii, P. tormentillae). Notably, N. ampelopsidis and P. tormentillae were discovered for the first time in China, while M. laricis-populina, Me. carpini, and Ny. koelreuteriae were first documented in Guizhou Province. Morphological observation and molecular phylogenetic analyses of these species with similar taxa were compared to confirm their taxonomic identities, and taxonomic descriptions, illustrations and host species of those rust fungi on medicinal plant are provided.
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- 2023
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9. A smart nanoplatform for enhanced photo-ferrotherapy of hepatocellular carcinoma
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Longguang Tang, Mingjian Ling, Madiha Zahra Syeda, Rui Sun, Minghui He, Qingchun Mu, Xiulong Zhu, Chunming Huang, and Liao Cui
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GSH ,ferrotherapy ,PTT ,hepatocellular carcinoma ,nanoparticle ,Biotechnology ,TP248.13-248.65 - Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients’ quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.
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- 2022
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10. FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors
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Lucía Peña-Pérez, Shabnam Kharazi, Nicolai Frengen, Aleksandra Krstic, Thibault Bouderlique, Julia Hauenstein, Minghui He, Ece Somuncular, Xiaoze Li Wang, Carin Dahlberg, Charlotte Gustafsson, Ann-Sofie Johansson, Julian Walfridsson, Nadir Kadri, Petter Woll, Marcin Kierczak, Hong Qian, Lisa Westerberg, Sidinh Luc, and Robert Månsson
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B cell ,FOXO (forkhead box protein O) ,lineage commitment/specification ,myeloid restriction ,gene regulation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.
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- 2022
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11. Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma
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Ning Zhang, Honglei Wang, Fang Wang, Chao Cheng, Shuling Chen, Xiaoyan Wang, Yong Bao, Sui Peng, Yaron Shargall, Fang Peng, Sai-Ching Jim Yeung, Biniam Kidane, Minghui He, Bo Zeng, Shiting Feng, Weixiong Yang, Xiangbin Xing, Siyu Wang, Wenfang Chen, Zhenguo Liu, Christopher W Seder, Kazuo Koyanagi, and Honghe Luo
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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12. N6-Methylandenosine-Related lncRNAs Predict Prognosis and Immunotherapy Response in Bladder Cancer
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Yuying Zhang, Baoyi Zhu, Minghui He, Yi Cai, Xiaoling Ying, Chonghe Jiang, Weidong Ji, and Jianwen Zeng
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bladder cancer ,N6-methyladenosine ,lncRNA ,prognosis ,tumor microenvironment ,immune response ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Both lncRNAs and the N6-methyladenosine (m6A) modification are key regulators of tumorigenesis and innate immunity. However, little is known about the m6A modification of lncRNAs and their clinical and immune relevance in bladder cancer. In this study, we identified m6A-related lncRNAs using Pearson correlation analysis in The Cancer Genome Atlas (TCGA) and the IMvigor210 datasets. Next, univariate Cox regression was performed using the TCGA dataset to filter prognostic m6A-related lncRNAs, which were further subjected to the least absolute shrinkage and selection operator (LASSO) Cox regression to establish a 12 m6A-related lncRNA prognostic score (m6A-LRS). The m6A-LRS was validated in the IMvigor210 dataset. In addition, high m6A-LRS tumors, characterized by decreased tumor mutation load and neoantigen load, showed poorer response to immunotherapy than those with low m6A-LRS in the IMvigor210 dataset. Further, we constructed an m6A-LRS-based nomogram that demonstrated a strong ability to predict overall survival in patients with bladder cancer. Moreover, enrichment analysis revealed that tumor-associated biological processes, oncogenic signaling, and tumor hallmarks were commonly associated with a high m6A-LRS. Gene set variation analysis also indicated that high m6A-LRS was associated with activation of canonical oncogenic signatures, such as the epithelial-to-mesenchymal transition, cell cycle regulators, and DNA replication, as well as activation of immunosuppressive signatures, such as the T-cell exhaustion and pan-fibroblast-TGF-β response signatures. Furthermore, we observed distinct tumor microenvironment cell infiltration characteristics between high- and low-risk tumors. High m6A-LRS tumors showed reduced infiltration of CD8+ T-cells and enhanced infiltration of macrophages and fibroblasts. Additionally, we established a competing endogenous RNA network based on the12 m6A-related lncRNAs. Finally, three lncRNAs (SNHG16, SBF2-AS1, and BDNF-AS) were selected for further validation. The qualitative PCR assay on 10 pairs of bladder cancer and adjacent normal control samples validated the differential expression, and methylated RNA immunoprecipitation (MeRIP) analysis demonstrated a robust m6A enrichment in T24 bladder cancer cells compared with normal uroepithelial cells (SVHUC-1). In conclusion, this study introduced an m6A-related lncRNA signature that identified a subgroup of patients with poor prognoses and suboptimal immune responses, thus providing novel approaches for treatment response prediction and patient stratification in bladder cancer.
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- 2021
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13. Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells
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Joanna S. Kritikou, Mariana M.S. Oliveira, Julien Record, Mezida B. Saeed, Saket M. Nigam, Minghui He, Marton Keszei, Arnika K. Wagner, Hanna Brauner, Anton Sendel, Saikiran K. Sedimbi, Stamatina Rentouli, David P. Lane, Scott B. Snapper, Klas Kärre, Peter Vandenberghe, Jordan S. Orange, and Lisa S. Westerberg
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Immunology ,Medicine - Abstract
X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich Syndrome protein (WASp). XLN patients have reduced numbers of cytotoxic cells in peripheral blood; however, their capacity to kill tumor cells remains to be determined. Here, we examined NK and T cells from 2 patients with XLN harboring the activating WASpL270P mutation. XLN patient NK and T cells had increased granzyme B content and elevated degranulation and IFN-γ production when compared with healthy control cells. Murine WASpL272P NK and T cells formed stable synapses with YAC-1 tumor cells and anti-CD3/CD28–coated beads, respectively. WASpL272P mouse T cells had normal degranulation and cytokine response whereas WASpL272P NK cells showed an enhanced response. Imaging experiments revealed that while WASpL272P CD8+ T cells had increased accumulation of actin upon TCR activation, WASpL272P NK cells had normal actin accumulation at lytic synapses triggered through NKp46 signaling but had impaired response to lymphocyte function associated antigen-1 engagement. When compared with WT mice, WASpL272P mice showed reduced growth of B16 melanoma and increased capacity to reject MHC class I–deficient cells. Together, our data suggest that cytotoxic cells with constitutively active WASp have an increased capacity to respond to and kill tumor cells.
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- 2021
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14. An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma
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Julien Record, Anton Sendel, Joanna S. Kritikou, Nikolai V. Kuznetsov, Hanna Brauner, Minghui He, Noemi Nagy, Mariana M.S. Oliveira, Elena Griseti, Christoph B. Haase, Jenny Dahlström, Sanjaykumar Boddul, Fredrik Wermeling, Adrian J. Thrasher, Chaohong Liu, John Andersson, Hans-Erik Claesson, Ola Winqvist, Siobhan O. Burns, Magnus Björkholm, and Lisa S. Westerberg
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together they regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom had been previously treated for Hodgkin lymphoma (HL). To investigate MKL1 and B-cell responses in the pathogenesis of HL, we generated Epstein-Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the patients with treated HL had a phenotype close to that of the healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This profile was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher proportion of cells with hyperploidy, and formed large tumors in vivo. This phenotype was reversible by inhibiting MKL1 activity. Interestingly, cells from the triplet treated for HL in 1985 contained two subpopulations: one with high expression of CD11a that behaved like control cells and the other with low expression of CD11a that formed large tumors in vivo similar to cells from the undiagnosed triplet. This implies that pre-malignant cells had re-emerged a long time after treatment. Together, these data suggest that dysregulated MKL1 activity participates in B-cell transformation and the pathogenesis of HL.
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- 2020
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15. Congenital Defects in Actin Dynamics of Germinal Center B Cells
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Minghui He and Lisa S. Westerberg
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germinal center ,B cell receptor ,immune synapse ,actin cytoskeleton ,antibodies ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The germinal center (GC) is a transient anatomical structure formed during the adaptive immune response that leads to antibody affinity maturation and serological memory. Recent works using two-photon microscopy reveals that the GC is a highly dynamic structure and GC B cells are highly motile. An efficient selection of high affinity B cells clones within the GC crucially relies on the interplay of proliferation, genome editing, cell-cell interaction, and migration. All these processes require actin cytoskeleton rearrangement to be well-coordinated. Dysregulated actin dynamics may impede on multiple stages during B cell affinity maturation, which could lead to aberrant GC response and result in autoimmunity and B cell malignancy. This review mainly focuses on the recent works that investigate the role of actin regulators during the GC response.
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- 2019
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16. Ovaries absent links dLsd1 to HP1a for local H3K4 demethylation required for heterochromatic gene silencing
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Fu Yang, Zhenghui Quan, Huanwei Huang, Minghui He, Xicheng Liu, Tao Cai, and Rongwen Xi
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Drosophila ovary ,HP1 ,LSD1 ,ovaries absent ,Heterochromatin ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Heterochromatin Protein 1 (HP1) is a conserved chromosomal protein in eukaryotic cells that has a major role in directing heterochromatin formation, a process that requires co-transcriptional gene silencing mediated by small RNAs and their associated argonaute proteins. Heterochromatin formation requires erasing the active epigenetic mark, such as H3K4me2, but the molecular link between HP1 and H3K4 demethylation remains unclear. In a fertility screen in female Drosophila, we identified ovaries absent (ova), which functions in the stem cell niche, downstream of Piwi, to support germline stem cell differentiation. Moreover, ova acts as a suppressor of position effect variegation, and is required for silencing telomeric transposons in the germline. Biochemically, Ova acts to link the H3K4 demethylase dLsd1 to HP1a for local histone modifications. Therefore, our study provides a molecular connection between HP1a and local H3K4 demethylation during HP1a-mediated gene silencing that is required for ovary development, transposon silencing, and heterochromatin formation.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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- 2019
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17. Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
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Yuanfeng Li, Lanlan Si, Yun Zhai, Yanling Hu, Zhibin Hu, Jin-Xin Bei, Bobo Xie, Qian Ren, Pengbo Cao, Fei Yang, Qingfeng Song, Zhiyu Bao, Haitao Zhang, Yuqing Han, Zhifu Wang, Xi Chen, Xia Xia, Hongbo Yan, Rui Wang, Ying Zhang, Chengming Gao, Jinfeng Meng, Xinyi Tu, Xinqiang Liang, Ying Cui, Ying Liu, Xiaopan Wu, Zhuo Li, Huifen Wang, Zhaoxia Li, Bo Hu, Minghui He, Zhibo Gao, Xiaobing Xu, Hongzan Ji, Chaohui Yu, Yi Sun, Baocai Xing, Xiaobo Yang, Haiying Zhang, Aihua Tan, Chunlei Wu, Weihua Jia, Shengping Li, Yi-Xin Zeng, Hongbing Shen, Fuchu He, Zengnan Mo, Hongxing Zhang, and Gangqiao Zhou
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Science - Abstract
This genome-wide association study on persistent hepatitis B virus (HBV) infection among Chinese confirms previously associated genetic loci while discovering a novel protective locus at 8p21.3. The study also demonstrates the nearby gene INST10 suppresses HBV replication in vitro.
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- 2016
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18. Wiskott-Aldrich syndrome gene mutations modulate cancer susceptibility in the p53± murine model
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Marton Keszei, Joanna S. Kritikou, Deborah Sandfort, Minghui He, Mariana M.S. Oliveira, Hannah Wurzer, Raoul V. Kuiper, and Lisa S. Westerberg
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wasp ,p53 ,malignancies ,genetic model ,immunodeficiency ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton in hematopoietic cells and mutated in two severe immunodeficiency diseases with high incidence of cancer. Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in WASp and most frequently associated with lymphoreticular tumors of poor prognosis. X-linked neuropenia (XLN) is caused by gain-of-function mutations in WASp and associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To understand the role of WASp in tumorigenesis, we bred WASp+, WASp−, and WASp-XLN mice onto tumor susceptible p53+/- background and sub-lethally irradiated them to enhance tumor development. We followed the cohorts for 24 weeks and tumors were characterized by histology and flow cytometry to define the tumor incidence, onset, and cell origin. We found that p53+/-WASp+ mice developed malignancies, including solid tumors and T cell lymphomas with 71.4% of survival 24 weeks after irradiation. p53+/-WASp− mice showed lower survival rate and developed various early onset malignancies. Surprisingly, the p53+/-WASp-XLN mice developed malignancy mostly with late onset, which caused delayed mortality in this colony. This study provides evidence for that loss-of-function and gain-of-function mutations in WASp influence tumor incidence and onset.
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- 2018
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19. The Small Rho GTPases Rac1 and Rac2 Are Important for T-Cell Independent Antigen Responses and for Suppressing Switching to IgG2b in Mice
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Natalija Gerasimčik, Minghui He, Carin I. M. Dahlberg, Nikolai V. Kuznetsov, Eva Severinson, and Lisa S. Westerberg
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B cells ,Rac1 ,Rac2 ,Ig class switching ,humoral immune response ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The Rho GTPases Cdc42, Rac1, and Rac2 coordinate receptor signaling to cell adhesion, migration, and proliferation. Deletion of Rac1 and Rac2 early during B cell development leads to failure in B cell entry into the splenic white pulp. Here, we sought to understand the role of Rac1 and Rac2 in B cell functionality and during the humoral antibody response. To circumvent the migratory deficiency of B cells lacking both Rac1 and Rac2, we took the approach to inducibly delete Rac1 in Rac2−/− B cells in the spleen (Rac1BRac2−/− B cells). Rac1BRac2−/− mice had normal differentiation of splenic B cell populations, except for a reduction in marginal zone B cells. Rac1BRac2−/− B cells showed normal spreading response on antibody-coated layers, while both Rac2−/− and Rac1BRac2−/− B cells had reduced homotypic adhesion and decreased proliferative response when compared to wild-type B cells. Upon challenge with the T-cell-independent antigen TNP-conjugated lipopolysaccharide, Rac1BRac2−/− mice showed reduced antibody response. In contrast, in response to the T-cell-dependent antigen sheep red blood cells, Rac1BRac2−/− mice had increased serum titers of IgG1 and IgG2b. During in vitro Ig class switching, Rac1BRac2−/− B cells had elevated germline γ2b transcripts leading to increased Ig class switching to IgG2b. Our data suggest that Rac1 and Rac2 serve an important role in regulation of the B cell humoral immune response and in suppressing Ig class switching to IgG2b.
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- 2017
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20. Deletion of Dock10 in B Cells Results in Normal Development but a Mild Deficiency upon In Vivo and In Vitro Stimulations
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Eva Severinson, Lisa S. Westerberg, Natalija Gerasimčik, Minghui He, and Marisa A. P. Baptista
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B cells ,Dock10 ,cytoskeleton ,gene expression ,humoral immune response ,Immunologic diseases. Allergy ,RC581-607 - Abstract
We sought to identify genes necessary to induce cytoskeletal change in B cells. Using gene expression microarray, we compared B cells stimulated with interleukin-4 (IL-4) and anti-CD40 antibodies that induce B cell spreading, cell motility, tight aggregates, and extensive microvilli with B cells stimulated with lipopolysaccharide that lack these cytoskeletal changes. We identified 84 genes with 10-fold or greater expression in anti-CD40 + IL-4 stimulated B cells, one of these encoded the guanine nucleotide exchange factor (GEF) dedicator of cytokinesis 10 (Dock10). IL-4 selectively induced Dock10 expression in B cells. Using lacZ expression to monitor Dock10 promoter activity, we found that Dock10 was expressed at all stages during B cell development. However, specific deletion of Dock10 in B cells was associated with a mild phenotype with normal B cell development and normal B cell spreading, polarization, motility, chemotaxis, aggregation, and Ig class switching. Dock10-deficient B cells showed lower proliferation in response to anti-CD40 and IL-4 stimulation. Moreover, the IgG response to soluble antigen in vivo was lower when Dock10 was specifically deleted in B cells. Together, we found that most B cell responses were intact in the absence of Dock10. However, specific deletion of Dock10 in B cells was associated with a mild reduction in B cell activation in vitro and in vivo.
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- 2017
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21. Stretchable and Wearable Triboelectric Nanogenerator Based on Kinesio Tape for Self-Powered Human Motion Sensing
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Shutang Wang, Minghui He, Bingjuan Weng, Lihui Gan, Yingru Zhao, Ning Li, and Yannan Xie
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triboelectric nanogenerator ,energy harvesting ,self-power active sensor ,flexible and wearable electronics ,biomechanical sensing ,Chemistry ,QD1-999 - Abstract
Recently, wearable, self-powered, active human motion sensors have attracted a great deal of attention for biomechanics, physiology, kinesiology, and entertainment. Although some progress has been achieved, new types of stretchable and wearable devices are urgently required to promote the practical application. In this article, targeted at self-powered active human motion sensing, a stretchable, flexible, and wearable triboelectric nanogenerator based on kinesio tapes (KT-TENG) haven been designed and investigated systematically. The device can effectively work during stretching or bending. Both the short-circuit transferred charge and open-circuit voltage exhibit an excellent linear relationship with the stretched displacements and bending angles, enabling its application as a wearable self-powered sensor for real-time human motion monitoring, like knee joint bending and human gestures. Moreover, the KT-TENG shows good stability and durability for long-term operation. Compared with the previous works, the KT-TENG without a macro-scale air gap inside, or stretchable triboelectric layers, possesses various advantages, such as simple fabrication, compact structure, superior flexibility and stability, excellent conformable contact with skin, and wide-range selection of triboelectric materials. This work provides a new prospect for a wearable, self-powered, active human motion sensor and has numerous potential applications in the fields of healthcare monitoring, human-machine interfacing, and prosthesis developing.
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- 2018
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22. Analysis of Lavandulyl Flavonoids from Sophora flavescens with Anti-inflammatory Activity Based on Molecular Network Technology.
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Yan LIN, Bo TU, Shanggao LIAO, and Minghui HE
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CHINESE medicine ,ANTI-inflammatory agents ,NANOTECHNOLOGY ,FLAVONOIDS ,SOPHORA - Abstract
[Objectives] This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens. [Methods] 35 compounds were screened from traditional Chinese medicine S. flavescens using the nitric oxide (NO) anti-inflammatory activity model. [Results] Five components, 8 (xanthohumol), 13 (kurarinol), 27 (4-methoxysalicylic acid), 28 (b-resorcic acid) and 30 (b-resorcic acid), exhibited significant anti-inflammatory activity, with IC
50 values of 5.99, 4.76, 6.96, 3.41 and 5.22 μM, respectively. Especially, 8 (xanthohumol) and 13 (kurarinol) were typical lavandulyl flavonoids in S. flavescens, which were worth further exploration. Furthermore, UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S. flavescens. A total of 15 components were identified. [Conclusions] This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S. flavescens. [ABSTRACT FROM AUTHOR]- Published
- 2024
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23. A New Flavonoid Glycoside from Polygonum capitatum.
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Lei HE, Yan LIN, Minghui HE, and Bo TU
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FLAVONOIDS ,ANTI-inflammatory agents ,ETHYL acetate ,POLYGONUM ,CATECHIN - Abstract
[Objectives] To discover novel compounds with significant anti-inflammatory activity in the alcohol extract of Polygonum capitatum. [Methods] Firstly, a new flavonoid glycoside,capitaone B (1), was isolated from the ethyl acetate extract from P. capitatum, and then 27 compounds were screened using NO anti-inflammatory activity model. [Results] Four compounds, such as kaempferol (12), 1,2, 6-trigalloyl-β-d-glucose (15), catechin (16) and β-sitosterol (26), could significantly inhibit LPS-induced NO production in macrophages, with IC50 values of 15.31, 8.43, 6.92 and 5.72 μM, respectively. [Conclusions] The chemical composition and anti-inflammatory activity of P. capitatum were preliminarily studied, and the results provide a theoretical basis for further research on the action mechanism of subsequent anti-inflammatory active compounds of P. capitatum. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Investigation on the Material Basis of Sijicao Granules in Treating Eczema Based on Network Pharmacology.
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Yitong SHEN, Bo TU, Yaru YANG, Li JIANG, Minghui HE, and Yan LIN
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ECZEMA ,GALLIC acid ,MOLECULAR docking ,CELL anatomy ,CELLULAR signal transduction - Abstract
Objectives] To explore the pharmacodynamic material basis of Sijicao granules for the treatment of eczema through chemical com- position-network pharmacology. [Methods] First of all, the chemical constituents of Polygonum capitatum and Plantago asiatica from Sijicao granules were collected, and the relevant target information of the constituents was collected by TCMSP, PubChem, DisGeNET, GeneCards and STRING databases. Furthermore, Cytoscape 3.8.2 software was used to construct the chemical compounds-target network map of Sijicao granules. Finally, STRING database was used for PPI protein network analysis, GO functional enrichment analysis and KEGG pathway enrich- ment analysis of core targets, and molecular docking between core constituents and protein targets was also performed. [Results] 30 constitu- ents, including quercetin, kaempferol, luteolin, ellagic acid and gallic acid, were discovered to be the key effective compounds of Sijicao gran- ules in the treatment of eczema. And its core action protein targets were PTGS2, NOS2, AKTI, TP53, IL6, HMOX1. What's more, through GO functional enrichment analysis of biological process (BP), cell component (CC), molecular function (MF) analysis and KEGG pathway enrichment analysis, the main pathways of action of Sijicao granules for the treatment of eczema including IL-17 signaling pathway, T cell re- ceptor signaling pathway, cancer signaling pathway, TNF signaling pathway and Relaxin signaling pathway. In addition, molecular docking re- sults displayed that the primary active constituents quercetin, kaempferol and luteolin were well combined with the core protein targets AKTI and IL6. [Conclusions] Sijicao granules could play an important role for the treatment of eczema through multi-component, multi-target, multi-pathway and their interaction. [ABSTRACT FROM AUTHOR]
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- 2023
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25. Systematic Evaluation of Pharmacognostic Identification of Polygonum capitatum.
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Bo TU, Xu ZHANG, Minghui HE, Shanggao LIAO, Yongqin ZENG, and Yan LIN
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CHEMICAL processes ,POLYGONUM ,CRYSTAL whiskers ,PLANT genomes ,POLLEN - Abstract
To investigate the systematic evaluation of pharmacognostic identification of Polygonum capitatum. [Methods] 10 batches of P. capitatum cultivated in Guizhou were chosen for plant samples. Macroscopical identification was conducted on plant roots, stems, leaves, flowers and fruits. The P. capitatum powder was processed for physical and chemical distinction by FeCl3 chromogenic reaction, hydrochloric acid magnesium powder reaction, A1C13 color development reaction and thin-layer chromatography. Microscope identification was carried out on the powder. Plant genome DNeasy Plant Kit was adopted for DNA molecular marker identification. [Results] The results showed that the stem of P. capitatum was tufted, the leaves were oval, 2 to 5 cm long, and 1 to 2 cm wide; the leaf apex was acute and cuneate at the base, the inflorescence was capitate, paired or solitary; the raceme was erect and nearly spherical, and the perianth was light red. Furthermore, for the chromogenic reaction of FeCl3 ethanol extract of P. capitatum, appeared blue and turned to dark blue after long time storing at room temperature. For the reaction of hydrochloric acid magnesium powder, the alcohol extract of P. capitatum, exhibited deep red. In the color reaction of A1C1, the alcohol extract revealed yellow fluorescence under 360 nm UV lamp. Microscope identification of the powder displayed pollen grains, crystal sheath fibers, cellulose, vessels, starch grains, cork cells, and other characteristic fragments. In addition, DNA barcoding electrophoresis results showed that P. capitatum showed a clear and bright single band near 500 bp, and further sequencing results showed that the sequence differences were mainly concentrated in 1TS1 and 1TS2 region. [Conclusions] Systematic evaluation for the identification of P. capitatum is established, which combines with macroscopic identification, physicochemical identification, powder microscope identification, and DNA molecular identification. Finally, the original medicinal material is identified as P. capitatum Buch. -Ham. ex D. Don. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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26. Distinct single-cell immune ecosystems distinguish true and de novo HBV-related hepatocellular carcinoma recurrences.
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Shuling Chen, Cheng Huang, Guanrui Liao, Huichuan Sun, Yubin Xie, Changyi Liao, Jianping Wang, Minghui He, Huanjing Hu, Zihao Dai, Xiaoxue Ren, Xuezhen Zeng, Zhilong Lin, Guo-Pei Zhang, Wenxuan Xie, Shunli Shen, Shaoqiang Li, Sui Peng, Dong-Ming Kuang, and Qiang Zhao
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CYTOTOXIC T cells ,T helper cells ,MONONUCLEAR leukocytes ,IMMUNE checkpoint proteins ,REGULATORY T cells - Published
- 2023
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27. CD36 and LC3B initiated autophagy in B cells regulates the humoral immune response
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Chikai Zhou, Saikiran K. Sedimbi, Lisa S. Westerberg, Jin Wang, Mikael C. I. Karlsson, Minghui He, Danai Lianoudaki, Marcus J.G.W. Ladds, Shuijie Li, Shan Wang, Chenfei He, and David P. Lane
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0301 basic medicine ,CD36 Antigens ,autophagy ,T-Lymphocytes ,ATG5 ,Plasma Cells ,Plasma cell ,03 medical and health sciences ,Mice ,Sequestosome 1 ,Immune system ,medicine ,Animals ,Humans ,education ,Molecular Biology ,B cell ,Cell Proliferation ,education.field_of_study ,B-Lymphocytes ,030102 biochemistry & molecular biology ,biology ,scavenger receptors ,Autophagosomes ,Germinal center ,Cell Differentiation ,Cell Biology ,b cell ,Immunoglobulin Class Switching ,Cell biology ,Immunity, Humoral ,030104 developmental biology ,medicine.anatomical_structure ,Autophagosome membrane ,Antibody response ,biology.protein ,Antibody ,class switching ,Microtubule-Associated Proteins ,Research Article ,Research Paper - Abstract
Scavenger receptors are pattern recognition receptors that recognize both foreign and self-ligands, and initiate different mechanisms of cellular activation, often as co-receptors. The function of scavenger receptor CD36 in the immune system has mostly been studied in macrophages but it is also highly expressed by innate type B cells where its function is less explored. Here we report that CD36 is involved in macro-autophagy/autophagy in B cells, and in its absence, the humoral immune response is impaired. We found that CD36-deficient B cells exhibit a significantly reduced plasma cell formation, proliferation, mitochondrial mobilization and oxidative phosphorylation. These changes were accompanied by impaired initiation of autophagy, and we found that CD36 regulated autophagy and colocalized with autophagosome membrane protein MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3). When we investigated T-cell-dependent immune responses, we found that mice with CD36 deficiency, specifically in B cells, exhibited attenuated germinal center responses, class switching, and antibody production as well as autophagosome formation. These findings establish a critical role for CD36 in B cell responses and may also contribute to our understanding of CD36-mediated autophagy in other cells as well as in B cell lymphomas that have been shown to express the receptor. Abbreviations: AICDA/AID: activation-induced cytidine deaminase; ATG5: autophagy related 5; ATP: adenosine triphosphate; BCR: B-cell receptor; CPG: unmethylated cytosine-guanosine; CQ: chloroquine; DC: dendritic cells; FOB: follicular B cells; GC: germinal center; Ig: immunoglobulin; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFI: mean fluorescence intensity; MZB: marginal zone B cells; NP-CGG: 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin; OCR: oxygen consumption rate; oxLDL: oxidized low-density lipoprotein; PC: plasma cells; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; SRBC: sheep red blood cells; Tfh: follicular helper T cells; TLR: toll-like receptor.
- Published
- 2021
28. Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation
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E.A. Deordieva, Lieselot Buedts, Lisa S. Westerberg, Chaohong Liu, Roberta D’Aulerio, Julien Record, Mezida B. Saeed, Peter Vandenberghe, Siobhan O. Burns, Lennart Hammarström, Marton Keszei, Larissa Vasconcelos-Fontes, Yu Xia, Chiara Geyer, Mariana M.S. Oliveira, Charlotte Cunningham-Rundles, Anna Shcherbina, Minghui He, Vinicius Cotta-de-Almeida, Lia Gonçalves Pinho, Lena Bohaumilitzky, Meike Thiemann, Dmitry Pershin, Rhaissa Vieira, Joao Pedro Lopes, Xiaodong Zhao, and Adrian J. Thrasher
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Neutropenia ,Wiskott–Aldrich syndrome ,Plasma Cells ,Immunology ,Naive B cell ,macromolecular substances ,Plasma cell ,Biology ,primary immunodeficiency ,plasma cells ,Affinity maturation ,Mice ,X-linked neutropenia ,medicine ,Animals ,Humans ,Immunology and Allergy ,B cell ,B-Lymphocytes ,B cells ,Cell growth ,Germinal center ,Genetic Diseases, X-Linked ,WASp ,medicine.disease ,Molecular biology ,Immunoglobulin A ,medicine.anatomical_structure ,Immunoglobulin class switching ,germinal center ,actin ,Cell Division ,Wiskott-Aldrich Syndrome Protein ,IgA - Abstract
BACKGROUND: B-cell affinity maturation in germinal center relies on regulated actin dynamics for cell migration and cell-to-cell communication. Activating mutations in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) cause X-linked neutropenia (XLN) with reduced serum level of IgA. OBJECTIVE: We investigated the role of B cells in XLN pathogenesis. METHODS: We examined B cells from 6 XLN patients, 2 of whom had novel R268W and S271F mutations in WASp. By using immunized XLN mouse models that carry the corresponding patient mutations, WASp L272P or WASp I296T, we examined the B-cell response. RESULTS: XLN patients had normal naive B cells and plasmablasts, but reduced IgA+ B cells and memory B cells, and poor B-cell proliferation. On immunization, XLN mice had a 2-fold reduction in germinal center B cells in spleen, but with increased generation of plasmablasts and plasma cells. In vitro, XLN B cells showed reduced immunoglobulin class switching and aberrant cell division as well as increased production of immunoglobulin-switched plasma cells. CONCLUSIONS: Overactive WASp predisposes B cells for premature differentiation into plasma cells at the expense of cell proliferation and immunoglobulin class switching. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:3 pages:1069-1084 ispartof: location:United States status: published
- Published
- 2022
29. Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells
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Mezida B. Saeed, Marton Keszei, Peter Vandenberghe, David P. Lane, Anton Sendel, Scott B. Snapper, Saket M. Nigam, Arnika Kathleen Wagner, Mariana M.S. Oliveira, Saikiran K. Sedimbi, Joanna S. Kritikou, Minghui He, Lisa S. Westerberg, Klas Kärre, Hanna Brauner, Julien Record, Jordan S. Orange, and Stamatina Rentouli
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0301 basic medicine ,Lymphocyte ,Immunology ,NK cells ,Research & Experimental Medicine ,Cell Degranulation ,Granzymes ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neoplasms ,MHC class I ,medicine ,Cytotoxic T cell ,Animals ,Cytoskeleton ,Actin ,Science & Technology ,biology ,Chemistry ,Degranulation ,General Medicine ,Cellular immune response ,Molecular biology ,Wiskott-Aldrich Syndrome ,Granzyme B ,030104 developmental biology ,medicine.anatomical_structure ,Medicine, Research & Experimental ,030220 oncology & carcinogenesis ,Case-Control Studies ,biology.protein ,Medicine ,Life Sciences & Biomedicine ,CD8 ,Wiskott-Aldrich Syndrome Protein ,T-Lymphocytes, Cytotoxic ,Research Article - Abstract
X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich Syndrome protein (WASp). XLN patients have reduced numbers of cytotoxic cells in peripheral blood; however, their capacity to kill tumor cells remains to be determined. Here, we examined NK and T cells from 2 patients with XLN harboring the activating WASpL270P mutation. XLN patient NK and T cells had increased granzyme B content and elevated degranulation and IFN-γ production when compared with healthy control cells. Murine WASpL272P NK and T cells formed stable synapses with YAC-1 tumor cells and anti-CD3/CD28-coated beads, respectively. WASpL272P mouse T cells had normal degranulation and cytokine response whereas WASpL272P NK cells showed an enhanced response. Imaging experiments revealed that while WASpL272P CD8+ T cells had increased accumulation of actin upon TCR activation, WASpL272P NK cells had normal actin accumulation at lytic synapses triggered through NKp46 signaling but had impaired response to lymphocyte function associated antigen-1 engagement. When compared with WT mice, WASpL272P mice showed reduced growth of B16 melanoma and increased capacity to reject MHC class I-deficient cells. Together, our data suggest that cytotoxic cells with constitutively active WASp have an increased capacity to respond to and kill tumor cells. ispartof: JCI INSIGHT vol:6 issue:6 ispartof: location:United States status: published
- Published
- 2021
30. β-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus
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Xiuling Fu, Jacob H. Hanna, Gang Ma, Jiajian Zhou, Liang Chen, Yunpan Li, Yan Qin, Axel Schambach, Vladislav Krupalnik, Hao Sun, Tian-Tian Zhou, Longqi Liu, Miguel A. Esteban, Fei Gao, Shuhan Chen, Hao Liu, Hui Zhang, Andrew P. Hutchins, Lulu Wang, Bradley W. Doble, Mazid Md. Abdul, Huating Wang, Xichen Bao, Yan Xu, Mengling Jiang, Shahzina Kanwal, Yiwei Lai, Christine Hartmann, Na Li, Xiangpeng Guo, Pengcheng Guo, Jie Yuan, Minghui He, Baoming Qin, David P. Ibañez, Umberto Di Vicino, Xueting Xu, Zhijun Yu, Wenjuan Li, Zhiwei Luo, Giacomo Volpe, Yuan Lv, Ao Jiang, Jianguo Zhou, Muqddas Tariq, Carl Ward, Guoliang Xu, Yayan Feng, Yinghua Huang, Guangming Wu, Dongye Wang, Isaac A. Babarinde, Karthik Arumugam, Runsheng Chen, Meng Zhang, and Maria Pia Cosma
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0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,Kinase ,SciAdv r-articles ,RNA polymerase II ,Cell Biology ,Embryonic stem cell ,Cell Cycle Gene ,3. Good health ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,GSK-3 ,Transcription (biology) ,030220 oncology & carcinogenesis ,biology.protein ,Protein kinase A ,Leukemia inhibitory factor ,Molecular Biology ,Research Articles ,030304 developmental biology ,Research Article - Abstract
β-Catenin recruits BRD4 and other coregulators to protect pluripotency gene transcription against network perturbation., Mouse embryonic stem cells cultured with MEK (mitogen-activated protein kinase kinase) and GSK3 (glycogen synthase kinase 3) inhibitors (2i) more closely resemble the inner cell mass of preimplantation blastocysts than those cultured with SL [serum/leukemia inhibitory factor (LIF)]. The transcriptional mechanisms governing this pluripotent ground state are unresolved. Release of promoter-proximal paused RNA polymerase II (Pol2) is a multistep process necessary for pluripotency and cell cycle gene transcription in SL. We show that β-catenin, stabilized by GSK3 inhibition in medium with 2i, supplies transcriptional coregulators at pluripotency loci. This selectively strengthens pluripotency loci and renders them addicted to transcription initiation for productive gene body elongation in detriment to Pol2 pause release. By contrast, cell cycle genes are not bound by β-catenin, and proliferation/self-renewal remains tightly controlled by Pol2 pause release under 2i conditions. Our findings explain how pluripotency is reinforced in the ground state and also provide a general model for transcriptional resilience/adaptation upon network perturbation in other contexts.
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- 2020
31. Exploring the Effect of Ligand-Originated MOF Isomerism and Methoxy Group Functionalization on Selective Acetylene/Methane and Carbon Dioxide/Methane Adsorption Properties in Two NbO-Type MOFs
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Xiaoxia Gao, Minghui He, Shunshun Xiong, Rajamani Krishna, Yabing He, Saidan Li, Yao Wang, and Chemical Reactor engineering (HIMS, FNWI)
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Materials science ,business.industry ,Ligand ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Methane ,0104 chemical sciences ,chemistry.chemical_compound ,Adsorption ,chemistry ,Chemical engineering ,Acetylene ,Natural gas ,Carbon dioxide ,Surface modification ,General Materials Science ,Metal-organic framework ,0210 nano-technology ,business - Abstract
Investigation of the impact of ligand-originated MOF (metal–organic framework) isomerism and ligand functionalization on gas adsorption is of vital importance because a study in this aspect provides valuable guidance for future fabrication of new MOFs exhibiting better performance. For the abovementioned purpose, two NbO-type ligand-originated MOF isomers based on methoxy-functionalized diisophthalate ligands were solvothermally constructed in this work. Their gas adsorption properties toward acetylene, carbon dioxide, and methane were systematically investigated, revealing their promising potential for the adsorptive separation of both acetylene/methane and carbon dioxide/methane gas mixtures, which are involved in the industrial processes of acetylene production and natural gas sweetening. In particular, compared to its isomer ZJNU-58, ZJNU-59 displays larger acetylene and carbon dioxide uptake capacities as well as higher acetylene/methane and carbon dioxide/methane adsorption selectivities despite its lower pore volume and surface area, demonstrating a very crucial role that the effect of pore size plays in acetylene and carbon dioxide adsorption. In addition, the impact of ligand modification with a methoxy group on gas adsorption was also evaluated. ZJNU-58 exhibits slightly lower acetylene and carbon dioxide uptake capacities but higher acetylene/methane and carbon dioxide/methane adsorption selectivities as compared to its parent compound NOTT-103. By contrast, enhanced adsorption selectivities and uptake capacities were observed for ZJNU-59 as compared to its parent compound ZJNU-73. The results demonstrated that the impact of ligand functionalization with a methoxy group on gas adsorption might vary from MOF to MOF, depending on the chosen parent compound. The results might shed some light on understanding the impact of both ligand-originated MOF isomerism and methoxy group functionalization on gas adsorption.
- Published
- 2018
32. Ovaries absent links dLsd1 to HP1a for local H3K4 demethylation required for heterochromatic gene silencing
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Tao Cai, Rongwen Xi, Minghui He, Fu Yang, Xicheng Liu, Huanwei Huang, and Zhenghui Quan
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Transposable element ,QH301-705.5 ,Heterochromatin ,Chromosomal Proteins, Non-Histone ,Science ,Drosophila ovary ,Population ,LSD1 ,Biology ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Germline ,Histones ,Research Communication ,Animals ,Drosophila Proteins ,Gene Silencing ,Biology (General) ,education ,Gene ,education.field_of_study ,General Immunology and Microbiology ,D. melanogaster ,HP1 ,General Neuroscience ,Lysine ,Stem Cells ,Ovary ,Oxidoreductases, N-Demethylating ,General Medicine ,Stem Cells and Regenerative Medicine ,Cell biology ,Demethylation ,Drosophila melanogaster ,Germ Cells ,ovaries absent ,Chromobox Protein Homolog 5 ,Medicine ,Heterochromatin protein 1 ,Female ,Stem cell ,Transcription Factors, General ,Protein Binding - Abstract
Heterochromatin Protein 1 (HP1) is a conserved chromosomal protein in eukaryotic cells that has a major role in directing heterochromatin formation, a process that requires co-transcriptional gene silencing mediated by small RNAs and their associated argonaute proteins. Heterochromatin formation requires erasing the active epigenetic mark, such as H3K4me2, but the molecular link between HP1 and H3K4 demethylation remains unclear. In a fertility screen in female Drosophila, we identified ovaries absent (ova), which functions in the stem cell niche, downstream of Piwi, to support germline stem cell differentiation. Moreover, ova acts as a suppressor of position effect variegation, and is required for silencing telomeric transposons in the germline. Biochemically, Ova acts to link the H3K4 demethylase dLsd1 to HP1a for local histone modifications. Therefore, our study provides a molecular connection between HP1a and local H3K4 demethylation during HP1a-mediated gene silencing that is required for ovary development, transposon silencing, and heterochromatin formation. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)., eLife digest The complete set of genetic material within a cell is known as a genome. The genomes of human and other animal cells have regions of active genes interspersed with ‘dark’ regions known as heterochromatin, which contain genes and other types of genetic material that have been inactivated. Heterochromatin commonly contains sections of genetic material known as transposons. When a transposon is active it is able to move around the genome, therefore, inactivating (or ‘silencing’) transposons helps to maintain the integrity of the genetic material in a cell. It is particularly important to silence transposons in the stem cells that produce sperm and egg cells – known as germline stem cells – to ensure genetic information is faithfully passed on to the next generation. A protein called HP1a plays a major role in directing where heterochromatin forms in the genome. This process requires an enzyme called dLsd1 to remove a small tag from the genetic material but it is not clear how HP1a regulates the activity of dLsd1. To address this question, Yang et al. studied how egg cells form in fruit flies, which are often used as models of animal biology in experiments. The team screened a population of fruit flies that carried mutations in many different genes to identify genes that affect the fertility of female flies. This revealed a gene named as ovaries absent (or ova for short) is required for egg cells to form. In germline stem cells ova silences transposons and in the surrounding tissue it represses a specific signal that usually maintains stem cells to allow the stem cells to divide to make egg cells. Further experiments using biochemical techniques found that the protein encoded by ova acts as a bridge to bring HP1a and dLsd1 together to silence genes in heterochromatin. The next step would be to identify the functional counterpart of the ova gene in mammals, including humans, which may help to discover causes of infertility and develop new fertility treatment.
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- 2019
33. Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma
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Yanbo Zhang, Chen Longyun, Xing Chen, Xuehan Zhuang, Jiansheng Guo, Jiaqian Wang, Zhi Xia, Fang Wang, Chao Chen, Jing Liu, Xiaolong Cheng, Sha Xie, Minghui He, Ruyi Shi, Qimin Zhan, Le Cheng, Xiangchun Li, Ling Zhang, Yongping Cui, Bin Li, Bin Yang, Yaoping Li, Xiaofeng Yang, Yunwei Ou, Bing Dong, Zhibo Gao, Qingshan Li, Jie Ma, Caixia Cheng, Wenliang Chen, Yanfeng Xi, Dongxin Lin, Yongjun Guo, Jinfen Wang, Mengyao Wang, Heyang Cui, Yong Zhou, Jiuzhou Zhao, Enming Li, Shengqing Wan, Xukui Yang, Lixin Liu, Jie Yang, Yingrui Li, Xuanlin Huang, Hongyi Li, Gang Chen, Guodong Li, Pengzhou Kong, Bin Song, Yin Li, Longhai Luo, Huanming Yang, Yanyan Zhang, Juan Wang, Jianfang Liang, Lin Li, Xiaoling Hu, Li-Yan Xu, Enwei Xu, Xiuqing Zhang, Zhenxiang Zhao, Yongkai Tan, Jun Wang, Yanghui Bi, Zhiwu Jia, and Yongmei Song
- Subjects
Esophageal Neoplasms ,Polycomb-Group Proteins ,Tetrazolium Salts ,Genome ,Ligases ,Phosphatidylinositol 3-Kinases ,Genetics(clinical) ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,Polycomb Repressive Complex 1 ,Genetics ,BAP1 ,LIM Domain Proteins ,CREB-Binding Protein ,Immunohistochemistry ,Hedgehog signaling pathway ,Patched-1 Receptor ,Gene Knockdown Techniques ,Carcinoma, Squamous Cell ,Esophageal Squamous Cell Carcinoma ,Erratum ,Ubiquitin Thiolesterase ,Signal Transduction ,Patched Receptors ,APOBEC ,China ,DNA Copy Number Variations ,Class I Phosphatidylinositol 3-Kinases ,APOBEC-1 Deaminase ,Ubiquitin-Protein Ligases ,Immunoblotting ,Molecular Sequence Data ,Receptors, Cell Surface ,Biology ,Real-Time Polymerase Chain Reaction ,Article ,Cell Line, Tumor ,Cytidine Deaminase ,Carcinoma ,medicine ,Humans ,Genetic Predisposition to Disease ,neoplasms ,Gene ,Analysis of Variance ,Base Sequence ,Genome, Human ,Tumor Suppressor Proteins ,Correction ,Sequence Analysis, DNA ,medicine.disease ,digestive system diseases ,Human genetics ,Thiazoles ,PTCH1 ,Mutation ,Transcription Factors - Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC -mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC -signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal ( CBX4 and CBX8 . In our combined cohort, we identified frequent inactivating mutations in AJUBA , ZNF750 , and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1 , in addition to known mutations. Functional analyses suggest roles for several genes ( CBX4 , CBX8 , AJUBA , and ZNF750 ) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.
- Published
- 2020
34. Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive
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Julien Record, David P. Lane, Minghui He, Wenxia Song, Jaime James, Scott B. Snapper, Carin I. M. Dahlberg, Chiara Geyer, Peter Vandenberghe, Paul Drescher, Sonia Lain, Marisa A. P. Baptista, Lisa S. Westerberg, Katrin Pütsep, Amlan Biswas, Hannah Wurzer, Meike Thiemann, Hanna Brauner, Marton Keszei, Laura Köcher, and Joanna S. Kritikou
- Subjects
0301 basic medicine ,Male ,Neutrophils ,Protein Conformation ,Research & Experimental Medicine ,Mice ,0302 clinical medicine ,Congenital Bone Marrow Failure Syndromes ,Gene Knock-In Techniques ,Phosphorylation ,PHOSPHORYLATION ,MUTATION ,IMMUNODEFICIENCY ,Chemistry ,SEVERE CONGENITAL NEUTROPENIA ,Genetic Diseases, X-Linked ,General Medicine ,Phenotype ,Cell biology ,ALDRICH-SYNDROME PROTEIN ,medicine.anatomical_structure ,Medicine, Research & Experimental ,030220 oncology & carcinogenesis ,Gain of Function Mutation ,Female ,Myelopoiesis ,Corrigendum ,Life Sciences & Biomedicine ,Wiskott-Aldrich Syndrome Protein ,Research Article ,Mice, 129 Strain ,Neutropenia ,Context (language use) ,Mice, Transgenic ,macromolecular substances ,Granulocyte ,03 medical and health sciences ,Phagocytosis ,INFLAMMATION ,medicine ,Animals ,Humans ,Congenital Neutropenia ,N-WASP ,ACTIN POLYMERIZATION ,PI3K/AKT/mTOR pathway ,Science & Technology ,medicine.disease ,Mice, Inbred C57BL ,BETA-ACTIN ,MICE ,030104 developmental biology - Abstract
Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand the pathophysiology in XLN and the role of WASp in neutrophils, we here examined XLN patients and 2 XLN mouse models. XLN patients had reduced myelopoiesis and extremely low blood neutrophil number. However, their neutrophils had a hyperactive phenotype and were present in normal numbers in XLN patient saliva. Murine XLN neutrophils were hyperactivated, with increased actin dynamics and migration into tissues. We provide molecular evidence that the hyperactivity of XLN neutrophils is caused by WASp in a constitutively open conformation due to contingent phosphorylation of the critical tyrosine-293 and plasma membrane localization. This renders WASp activity less dependent on regulation by PI3K. Our data show that the amplitude of WASp activity inside a cell could be enhanced by cell-surface receptor signaling even in the context in which WASp is already in an active conformation. Moreover, these data categorize XLN as an atypical congenital neutropenia in which constitutive activation of WASp in tissue neutrophils compensates for reduced myelopoiesis. ispartof: JOURNAL OF CLINICAL INVESTIGATION vol:128 issue:9 pages:4115-4131 ispartof: location:United States status: published
- Published
- 2018
35. Stretchable and Wearable Triboelectric Nanogenerator Based on Kinesio Tape for Self-Powered Human Motion Sensing
- Author
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Yannan Xie, Lihui Gan, Ning Li, Minghui He, Yingru Zhao, Shutang Wang, and Bingjuan Weng
- Subjects
energy harvesting ,Computer science ,General Chemical Engineering ,Wearable computer ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,lcsh:Chemistry ,self-power active sensor ,General Materials Science ,Wearable technology ,Triboelectric effect ,business.industry ,triboelectric nanogenerator ,Nanogenerator ,Electrical engineering ,Conformable matrix ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,biomechanical sensing ,lcsh:QD1-999 ,Interfacing ,0210 nano-technology ,business ,flexible and wearable electronics ,Energy harvesting ,Voltage - Abstract
Recently, wearable, self-powered, active human motion sensors have attracted a great deal of attention for biomechanics, physiology, kinesiology, and entertainment. Although some progress has been achieved, new types of stretchable and wearable devices are urgently required to promote the practical application. In this article, targeted at self-powered active human motion sensing, a stretchable, flexible, and wearable triboelectric nanogenerator based on kinesio tapes (KT-TENG) haven been designed and investigated systematically. The device can effectively work during stretching or bending. Both the short-circuit transferred charge and open-circuit voltage exhibit an excellent linear relationship with the stretched displacements and bending angles, enabling its application as a wearable self-powered sensor for real-time human motion monitoring, like knee joint bending and human gestures. Moreover, the KT-TENG shows good stability and durability for long-term operation. Compared with the previous works, the KT-TENG without a macro-scale air gap inside, or stretchable triboelectric layers, possesses various advantages, such as simple fabrication, compact structure, superior flexibility and stability, excellent conformable contact with skin, and wide-range selection of triboelectric materials. This work provides a new prospect for a wearable, self-powered, active human motion sensor and has numerous potential applications in the fields of healthcare monitoring, human-machine interfacing, and prosthesis developing.
- Published
- 2018
36. Deletion of Dock10 in B Cells Results in Normal Development but a Mild Deficiency upon In Vivo and In Vitro Stimulations
- Author
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Minghui He, Marisa A. P. Baptista, Eva Severinson, Natalija Gerasimcik, and Lisa S. Westerberg
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,B-cell receptor ,Naive B cell ,Immunology ,Atacicept ,Dock10 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Immunology and Allergy ,B cell ,B cells ,CD40 ,biology ,cytoskeleton ,medicine.disease ,Molecular biology ,humoral immune response ,030104 developmental biology ,medicine.anatomical_structure ,Immunoglobulin class switching ,biology.protein ,gene expression ,Antibody ,lcsh:RC581-607 ,Cytokinesis ,030215 immunology - Abstract
We sought to identify genes necessary to induce cytoskeletal change in B cells. Using gene expression microarray, we compared B cells stimulated with Interleukin-4 (IL-4) and anti-CD40 antibodies that induce B cell spreading, cell motility, tight aggregates, and extensive microvilli with B cells stimulated with lipopolysaccharide that lack these cytoskeletal changes. We identified 84 genes with 10-fold or greater expression in anti-CD40+IL-4 stimulated B cells, one of these encoded the guanidine nucleotide exchange factor (GEF) dedicator of cytokinesis 10 (Dock10). IL-4 selectively induced Dock10 expression in B cells. Using lacZ expression to monitor Dock10 promoter activity, we found that Dock10 was expressed at all stages during B cell development. However, specific deletion of Dock10 in B cells was associated with a mild phenotype with normal B cell development and normal B cell spreading, polarization, motility, chemotaxis, aggregation, and Ig class switching. Dock10 deficient B cells showed lower proliferation in response to anti-CD40 and IL-4 stimulation. Moreover, the IgG response to soluble antigen in vivo was lower when Dock10 was specifically deleted in B cells. Together, we found that most B cell responses were intact in the absence of Dock10. However, specific deletion of Dock10 in B cells was associated with a mild reduction in B cell activation in vitro and in vivo.
- Published
- 2017
- Full Text
- View/download PDF
37. Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
- Author
-
Pengbo Cao, Xiaobo Yang, Xinyi Tu, Gangqiao Zhou, Zhibin Hu, Jin Xin Bei, Chaohui Yu, Haiying Zhang, Ying Liu, Xia Xia, Zengnan Mo, Haitao Zhang, Qian Ren, Ying Cui, Xi Chen, Aihua Tan, Fuchu He, Yi Xin Zeng, Jin-feng Meng, Bobo Xie, Wei Hua Jia, Qingfeng Song, Chunlei Wu, Chengming Gao, Yuanfeng Li, Xiaopan Wu, Hongxing Zhang, Zhuo Li, Yanling Hu, Xiaobing Xu, Rui Wang, Hongbo Yan, Xinqiang Liang, Zhifu Wang, Minghui He, Yun Zhai, Bo Hu, Zhiyu Bao, Fei Yang, Ying Zhang, Zhibo Gao, Hongzan Ji, Lanlan Si, Zhaoxia Li, Hongbing Shen, Huifen Wang, Yuqing Han, Shengping Li, Baocai Xing, and Yi Sun
- Subjects
0301 basic medicine ,Adult ,Male ,Hepatitis B virus ,Science ,General Physics and Astronomy ,Genome-wide association study ,Locus (genetics) ,Biology ,medicine.disease_cause ,Virus Replication ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,03 medical and health sciences ,Young Adult ,Hepatitis B, Chronic ,Asian People ,medicine ,Humans ,Genetic Predisposition to Disease ,Serologic Tests ,Gene ,Aged ,Multidisciplinary ,Hepatitis B Surface Antigens ,virus diseases ,General Chemistry ,Odds ratio ,Middle Aged ,Viral Load ,Virology ,030104 developmental biology ,Liver ,Infectious disease (medical specialty) ,Genetic Loci ,Case-Control Studies ,Immunology ,Expression quantitative trait loci ,Hepatocytes ,Female ,Interferon Regulatory Factor-3 ,IRF3 ,Carrier Proteins ,Chromosomes, Human, Pair 8 ,Genome-Wide Association Study - Abstract
Hepatitis B virus (HBV) infection is a common infectious disease. Here we perform a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci involved in persistent HBV infection. GWAS scan is performed in 1,251 persistently HBV infected subjects (PIs, cases) and 1,057 spontaneously recovered subjects (SRs, controls), followed by replications in four independent populations totally consisting of 3,905 PIs and 3,356 SRs. We identify a novel locus at 8p21.3 (index rs7000921, odds ratio=0.78, P=3.2 × 10−12). Furthermore, we identify significant expression quantitative trait locus associations for INTS10 gene at 8p21.3. We demonstrate that INST10 suppresses HBV replication via IRF3 in liver cells. In clinical plasma samples, we confirm that INST10 levels are significantly decreased in PIs compared with SRs, and negatively correlated with the HBV load. These findings highlight a novel antiviral gene INTS10 at 8p21.3 in the clearance of HBV infection., This genome-wide association study on persistent hepatitis B virus (HBV) infection among Chinese confirms previously associated genetic loci while discovering a novel protective locus at 8p21.3. The study also demonstrates the nearby gene INST10 suppresses HBV replication in vitro.
- Published
- 2016
38. Whole Exome Sequencing Identifies Frequent Somatic Mutations in Cell-Cell Adhesion Genes in Chinese Patients with Lung Squamous Cell Carcinoma
- Author
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Jufeng Xia, Xiuqing Zhang, Liangtao Zheng, Hang Wang, Tingyan Shi, Yong Zhou, Xueda Hu, Chenguang Li, Menghong Sun, Rong Fang, Jun He, Li-Xin Qiu, Xiaoyang Luo, Jing He, Ruoxin Zhang, Ye Yin, Renhua Wu, Xiangchun Li, Yihua Sun, Lin Li, Ting Ye, Fuming Li, Haichuan Hu, Mingbang Wang, Li Jin, Cun Yu Wang, Shilin Tian, Jingya Lu, Fei Li, Qiang Feng, Jun Wang, Rui Wang, Xiaonan Yang, Zhibo Gao, Yunjian Pan, Yingrui Li, Guangwu Guo, Mengyun Wang, Chen Longyun, Huanming Yang, Meiling Zhu, Asan, Qingyi Wei, Bin Wang, Haiquan Chen, Qiaoxiu Wang, Minghui He, Hongbin Ji, Guangliang Yin, Qin Wang, Dan Li, and Xiaoyan Zhou
- Subjects
Pathology ,medicine.medical_specialty ,China ,Lung Neoplasms ,Somatic cell ,Biology ,medicine.disease_cause ,Article ,medicine ,Cell Adhesion ,PTEN ,Humans ,Exome ,Genes, Tumor Suppressor ,Lung cancer ,Exome sequencing ,Multidisciplinary ,Cell growth ,Wnt signaling pathway ,medicine.disease ,Mutation ,Cancer research ,biology.protein ,Carcinoma, Squamous Cell ,Carcinogenesis ,Sequence Analysis - Abstract
Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21% and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy.
- Published
- 2015
39. Highly Stretchable and Compressible Cellulose Ionic Hydrogels for Flexible Strain Sensors.
- Author
-
Ruiping Tong, Guangxue Chen, Danhong Pan, Haisong Qi, Ren'ai Li, Junfei Tian, Fachuang Lu, and Minghui He
- Published
- 2019
- Full Text
- View/download PDF
40. Stretchable andWearable Triboelectric Nanogenerator Based on Kinesio Tape for Self-Powered Human Motion Sensing.
- Author
-
Shutang Wang, Minghui He, Bingjuan Weng, Lihui Gan, Yingru Zhao, Ning Li, and Yannan Xie
- Subjects
BIOMECHANICS ,MOTION detectors ,OPEN-circuit voltage - Abstract
Recently, wearable, self-powered, active human motion sensors have attracted a great deal of attention for biomechanics, physiology, kinesiology, and entertainment. Although some progress has been achieved, new types of stretchable and wearable devices are urgently required to promote the practical application. In this article, targeted at self-powered active human motion sensing, a stretchable, flexible, and wearable triboelectric nanogenerator based on kinesio tapes (KT-TENG) haven been designed and investigated systematically. The device can effectively work during stretching or bending. Both the short-circuit transferred charge and open-circuit voltage exhibit an excellent linear relationship with the stretched displacements and bending angles, enabling its application as a wearable self-powered sensor for real-time human motion monitoring, like knee joint bending and human gestures. Moreover, the KT-TENG shows good stability and durability for long-term operation. Compared with the previous works, the KT-TENG without a macro-scale air gap inside, or stretchable triboelectric layers, possesses various advantages, such as simple fabrication, compact structure, superior flexibility and stability, excellent conformable contact with skin, and wide-range selection of triboelectric materials. This work provides a new prospect for a wearable, self-powered, active human motion sensor and has numerous potential applications in the fields of healthcare monitoring, human-machine interfacing, and prosthesis developing. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
41. Engineering Biocompatible Hydrogels from Bicomponent Natural Nanofibers for Anticancer Drug Delivery.
- Author
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Junfei Xu, Shan Liu, Guangxue Chen, Ting Chen, Tao Song, Jing Wu, Congcan Shi, Minghui He, and Junfei Tian
- Published
- 2018
- Full Text
- View/download PDF
42. The Small Rho GTPases Rac1 and Rac2 Are Important for T-Cell Independent Antigen Responses and for Suppressing Switching to IgG2b in Mice.
- Author
-
Gerasimčik, Natalija, Minghui He, Dahlberg, Carin I. M., Kuznetsov, Nikolai V., Severinson, Eva, and Westerberg, Lisa S.
- Subjects
RHO GTPases ,T cell receptors ,IMMUNOGLOBULIN G - Abstract
The Rho GTPases Cdc42, Rac1, and Rac2 coordinate receptor signaling to cell adhesion, migration, and proliferation. Deletion of Rac1 and Rac2 early during B cell development leads to failure in B cell entry into the splenic white pulp. Here, we sought to understand the role of Rac1 and Rac2 in B cell functionality and during the humoral antibody response. To circumvent the migratory deficiency of B cells lacking both Rac1 and Rac2, we took the approach to inducibly delete Rac1 in Rac2
-/- B cells in the spleen (Rac1B Rac2-/- B cells). Rac1B Rac2-/- mice had normal differentiation of splenic B cell populations, except for a reduction in marginal zone B cells. Rac1B Rac2-/- B cells showed normal spreading response on antibody-coated layers, while both Rac2-/- and Rac1B Rac2-/- B cells had reduced homotypic adhesion and decreased proliferative response when compared to wild-type B cells. Upon challenge with the T-cell-independent antigen TNP-conjugated lipopolysaccharide, Rac1B Rac2-/- mice showed reduced antibody response. In contrast, in response to the T-cell-dependent antigen sheep red blood cells, Rac1B Rac2-/- mice had increased serum titers of IgG1 and IgG2b. During in vitro Ig class switching, Rac1B Rac2-/- B cells had elevated germline γ2b transcripts leading to increased Ig class switching to IgG2b. Our data suggest that Rac1 and Rac2 serve an important role in regulation of the B cell humoral immune response and in suppressing Ig class switching to IgG2b. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
43. Extraction Optimization and Composition Analysis of Volatile Oil from Fruit of Alpinia zerumbet.
- Author
-
Xu ZHANG, Minghui HE, Weiyao ZHENG, Xu CUI, and Qingde LONG
- Subjects
- *
ALPINIA , *OIL & fat extraction , *FRUIT composition , *ORTHOGONAL systems , *MATHEMATICAL optimization - Abstract
[Objectives] The aim was to determine the optimum process for the extraction of volatile oil from Alpinia zerumbet fruit. [Methods] Steam distiilation was used to extract volatile oil from A. zerumbet fruit. Based on the single factor tests, an orthogonal test was designed to explore the effects of solid-liquid ratio, soaking time, extraction time and grinding degree of material on the extraction rate. The composition of volatile oil from A. zerumbet fruit was analyzed using gas chromatography-mass spectrometry (GC-MS), and the relative mass fraction of each component was determined by peak area normalization. [Results] With volatile oil yield as the index, the optimum extraction process was determined: solid to liquid ratio of 1:10, soaking time of 0.5 h, grinding degree of passing through 24-mesh sieve and extraction time of 5 h. A total of 29 compounds were isolated. Among them, the contents of a-terpinene (24. 894%), 1, 8-terpadiene (15.527%) and α-pinene (6. 982%) were relatively high. [Conclusions] The optimized extraction process for volatile oil from A. zerumbet fruit is stable and reasonable. Under the optimum extraction process, the extraction effect of volatile oil from A. zerumbet fruit was the best. The chemical components of volatile oil from A. zerumbet fruit were determined by GC-MS as α-terpinene (24. 894%), 1, 8-terpadiene (15.527%) and α-pinene (6.982%). [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
44. A Novel Mouse Model for the Hyper-IgM Syndrome: A Spontaneous Activation-Induced Cytidine Deaminase Mutation Leading to Complete Loss of Ig Class Switching and Reduced Somatic Hypermutation.
- Author
-
Dahlberg, Carin I. M., Minghui He, Visnes, Torkild, Torres, Magda Liz, Cortizas, Elena M., Verdun, Ramiro E., Westerberg, Lisa S., Severinson, Eva, and Ström, Lena
- Subjects
- *
IMMUNOLOGIC diseases , *IMMUNOGLOBULIN M , *CYTIDINE deaminase , *LABORATORY mice , *ENZYME activation , *GENETIC mutation , *NATURAL immunity - Abstract
We describe a spontaneously derived mouse line that completely failed to induce Ig class switching in vitro and in vivo. The mice inherited abolished IgG serum titers in a recessive manner caused by a spontaneous G→A transition mutation in codon 112 of the aicda gene, leading to an arginine to histidine replacement (AIDR112H). Ig class switching was completely reconstituted by expressing wild-type AID. Mice homozygous for AIDR112H had peripheral B cell hyperplasia and large germinal centers in the absence of Ag challenge. Immunization with SRBCs elicited an Ag-specific IgG1 response in wild-type mice, whereas AIDR112H mice failed to produce IgG1 and had reduced somatic hypermutation. The phenotype recapitulates the human hyper-IgM (HIGM) syndrome that is caused by point mutations in the orthologous gene in humans, and the AIDR112H mutation is frequently found in HIGM patients. The AIDR112H mouse model for HIGM provides a powerful and more precise tool than conventional knockout strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
45. Flexible thermoelectric nanogenerator based on the MoS2/graphene nanocomposite and its application for a self-powered temperature sensor.
- Author
-
Yannan Xie, Ting-Mao Chou, Weifeng Yang, Minghui He, Yingru Zhao, Ning Li, and Zong-Hong Lin
- Subjects
THERMOELECTRIC generators ,GRAPHENE ,NANOCOMPOSITE materials ,TEMPERATURE sensors ,ELECTRIC conductivity ,CHARGE transfer - Abstract
In this work, we report on a flexible thermoelectric nanogenerator (NG) based on the MoS
2 /graphene nanocomposite. The nanocomposite thermoelectric nanogenerator shows enhanced thermoelectric performance, compared with that based solely on MoS2 nanomaterials, which may be due to the enhanced electrical conductivity resulting from the graphene acting as a charge transfer channel in the composites. The NG can be further applied as a self-powered sensor for temperature measurement. This work indicates that the MoS2 /graphene nanocomposite is a promising thermoelectric material for harvesting environmental thermal energy. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
46. Cobalt-Catalyzed Monoselective Ortho-C-H Functionalization of Carboxamides with Organoaluminum Reagent.
- Author
-
Huiqiao Wang, Sheng Zhang, Zhiqiang Wang, Minghui He, and Kun Xu
- Published
- 2016
- Full Text
- View/download PDF
47. Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive.
- Author
-
Keszei, Marton, Record, Julien, Kritikou, Joanna S., Wurzer, Hannah, Geyer, Chiara, Thiemann, Meike, Drescher, Paul, Brauner, Hanna, Köcher, Laura, James, Jaime, Minghui He, Baptista, Marisa A. P., Dahlberg, Carin I. M., Biswas, Amlan, Lain, Sonia, Lane, David P., Wenxia Song, Pütsep, Katrin, Vandenberghe, Peter, and Snapper, Scott B.
- Subjects
- *
NEUTROPENIA , *NEUTROPHIL immunology , *BACTERIAL diseases -- Immunological aspects , *GRANULOCYTES , *WISKOTT-Aldrich syndrome - Abstract
Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand the pathophysiology in XLN and the role of WASp in neutrophils, we here examined XLN patients and 2 XLN mouse models. XLN patients had reduced myelopoiesis and extremely low blood neutrophil number. However, their neutrophils had a hyperactive phenotype and were present in normal numbers in XLN patient saliva. Murine XLN neutrophils were hyperactivated, with increased actin dynamics and migration into tissues. We provide molecular evidence that the hyperactivity of XLN neutrophils is caused by WASp in a constitutively open conformation due to contingent phosphorylation of the critical tyrosine-293 and plasma membrane localization. This renders WASp activity less dependent on regulation by PI3K. Our data show that the amplitude of WASp activity inside a cell could be enhanced by cell-surface receptor signaling even in the context in which WASp is already in an active conformation. Moreover, these data categorize XLN as an atypical congenital neutropenia in which constitutive activation of WASp in tissue neutrophils compensates for reduced myelopoiesis. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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