109 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
- Full Text
- View/download PDF
22. Computation-assisted SiteFinding- PCR for isolating flanking sequence tags in rice
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Hongru Wang, Jun Fang, Chengzheng Liang, Minghui He, Qiye Li, and Chengcai Chu
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SiteFinding-PCR ,flanking sequences ,chromosome walking ,rice ,Biology (General) ,QH301-705.5 - Abstract
SiteFinding-PCR is a method for isolating flanking sequence tags (FSTs) of T-DNA insertion lines, but the efficiency needs to be improved. Here we report a computation-assisted design for the random primers used in SiteFinding- PCR. A short sequence, GCATG, was screened from the rice genome and used as the 3′ end of the random primer. When applying the optimized primer for isolating FSTs from 168 transgenic rice lines, we obtained 107 specific products, including 64 FSTs. The efficiency of obtaining FSTs using the modified version of SiteFinding-PCR increased by 73.0% compared with the method previously reported (P < 0.01, µ test). We also provide computational results for several other plant species such as maize, sorghum, Arabidopsis, foxtail millet, and Brachypodium based on the available genome data, so that the modified method could be easily adapted to other species.
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- 2011
- Full Text
- View/download PDF
23. Research on inertial reference units prescribed performance integral sliding mode angle control
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Ling Zhao, Minghui He, and Xinyue Cao
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Atmospheric Science ,Geophysics ,Space and Planetary Science ,Aerospace Engineering ,General Earth and Planetary Sciences ,Astronomy and Astrophysics - Published
- 2023
24. Increased cross-presentation by dendritic cells and enhanced anti-tumour therapy using the Arp2/3 inhibitor CK666
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Mariana M. S. Oliveira, Roberta D’Aulerio, Tracer Yong, Minghui He, Marisa A. P. Baptista, Susanne Nylén, and Lisa S. Westerberg
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Cancer Research ,Oncology - Abstract
Background Dendritic cell (DC) vaccines for cancer therapy offer the possibility to let the patient’s own immune system kill cancer cells. However, DC vaccines have shown less efficacy than expected due to failure to induce cancer cell killing and by activating T regulatory cells. Methods We tested if inhibition of signalling via WASp and Arp2/3 using the small molecule CK666 would enhance DC-mediated killing of tumour cells in vitro and in vivo. Results Using CK666 during the ex vivo phase of antigen processing of ovalbumin (OVA), murine and human DCs showed decreased phagosomal acidification, indicating activation of the cross-presentation pathway. When compared to untreated DCs, DCs treated with CK666 during uptake and processing of OVA-induced increased proliferation of OVA-specific CD8+ OT-I T cells in vitro and in vivo. Using the aggressive B16-mOVA melanoma tumour model, we show that mice injected with CK666-treated DCs and OVA-specific CD8+ OT-I T cells showed higher rejection of B16 melanoma cells when compared to mice receiving non-treated DCs. This resulted in the prolonged survival of tumour-bearing mice receiving CK666-treated DCs. Moreover, combining CK666-treated DCs with the checkpoint inhibitor anti-PD1 further prolonged survival. Conclusion Our data suggest that the small molecule inhibitor CK666 is a good candidate to enhance DC cross-presentation for cancer therapy.
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- 2023
25. Supplementary Figure from Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma
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Ming Kuang, Zhenwei Peng, Baogang Peng, Jiaming Lai, Dongming Li, Shunli Shen, Shaoqiang Li, Lixia Xu, Jiehui Tan, Zelong Liu, Zihao Dai, Xiangjun Zhou, Xiaoshuang Li, Yifan Ma, Longqing Tang, Yanyan Han, Minghui He, Huanjing Hu, Yubin Xie, Bin Li, Qian Zhou, Han Xiao, Zebin Chen, Wei Wang, Tianhong Su, Xuezhen Zeng, Jie Mei, Wei Hu, Shuling Chen, and Sui Peng
- Abstract
Supplementary Figure from Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma
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- 2023
26. Data from Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma
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Ming Kuang, Zhenwei Peng, Baogang Peng, Jiaming Lai, Dongming Li, Shunli Shen, Shaoqiang Li, Lixia Xu, Jiehui Tan, Zelong Liu, Zihao Dai, Xiangjun Zhou, Xiaoshuang Li, Yifan Ma, Longqing Tang, Yanyan Han, Minghui He, Huanjing Hu, Yubin Xie, Bin Li, Qian Zhou, Han Xiao, Zebin Chen, Wei Wang, Tianhong Su, Xuezhen Zeng, Jie Mei, Wei Hu, Shuling Chen, and Sui Peng
- Abstract
A high rate of recurrence after curative therapy is a major challenge for the management of hepatocellular carcinoma (HCC). Currently, no effective adjuvant therapy is available to prevent HCC recurrence. We designed a personalized neoantigen-loaded dendritic cell vaccine and neoantigen-activated T-cell therapy, and used it as adjuvant therapy to treat 10 patients with HCC who had undergone curative resection or radiofrequency ablation in the first stage of a phase II trial (NCT03067493). The primary outcomes were safety and neoantigen-specific immune response. Disease-free survival (DFS) was also evaluated. The immunotherapy was successfully administered to all the patients without unexpected delay and demonstrated a reasonable safety profile with no grade ≥3 treatment-related side effects reported. Seventy percent of patients generated de novo circulating multiclonal neoantigen-specific T-cell responses. Induced neoantigen-specific immunity was maintained over time, and epitope spreading was observed. Patients who generated immune responses to treatment exhibited prolonged DFS compared with nonresponders (P = 0.012), with 71.4% experiencing no relapse for 2 years after curative treatment. High expression of an immune stimulatory signature, enhanced immune-cell infiltration (i.e., CD8+ T cells), and upregulated expression of T-cell inflammatory gene profiles were found in the primary tumors of the responders. In addition, neoantigen depletion (immunoediting) was present in the recurrent tumors compared with the primary tumors (7/9 vs. 1/17, P = 0.014), suggesting that immune evasion occurred under the pressure of immunotherapy. Our study indicates that neoantigen-based combination immunotherapy is feasible, safe, and has the potential to reduce HCC recurrence after curative treatment.
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- 2023
27. Table S5 from The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas
- Author
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Sui Peng, Lixia Xu, Ming Kuang, Jun Yu, Lijian Liang, Baogang Peng, Dongming Li, Lujing Fang, Han Xiao, Xiaoxing Li, Yubin Xie, Shunli Shen, Heping Li, Yu Guo, Minghui He, and Manling Huang
- Abstract
Table S5 shows detailed information of structure variations in the six HCC patients with WGS analysis.
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- 2023
28. Figure S1-S17 from The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas
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Sui Peng, Lixia Xu, Ming Kuang, Jun Yu, Lijian Liang, Baogang Peng, Dongming Li, Lujing Fang, Han Xiao, Xiaoxing Li, Yubin Xie, Shunli Shen, Heping Li, Yu Guo, Minghui He, and Manling Huang
- Abstract
Fig.S1 shows flow chart of enrollment for multifocal HCC patients with anti-PD-1 therapy. Fig.S2 shows CT images of the six HCC patients with two tumors in the liver. Fig.S3 shows purity of tumor content of the six HCC patients with two tumors in the liver. Fig.S4 shows HBV integration sites in the six HCC patients with two tumors in the liver. Fig.S5 shows expression level of TERT in the six HCC patients with two tumors in the liver. Fig.S6 shows landscape of inter-chromosomal translocations and copy number alterations in small and large tumors of four cases. Fig.S7 shows number and types of chromosomal rearrangement in the six HCC patients with two tumors in the liver. Fig.S8 shows copy number aberrations in the six HCC patients with two tumors in the liver. Fig.S9 shows mutational landscape of the six HCC patients with two tumors in the liver. Fig.S10 shows non-silent mutations in the six HCC patients with two tumors in the liver. Fig.S11 shows profile of mutational cancer cell fractions of small and large tumors in the six HCC patients. Fig.S12 shows unsupervised clustering of RNA expression in tumors and adjacent normal liver tissues of 12 multifocal HCC patients. Fig.S13 shows expression level of immune functional genes in small and large tumors of 12 multifocal HCC patients. Fig.S14 shows expression level of immune stimulators in small and large tumors of 12 multifocal HCC patients. Fig.S15 shows expression level of immune inhibitors in small and large tumors of 12 multifocal HCC patients. Fig.S16 shows mutations of immune-related genes in the six HCC patients with two tumor nodules in the liver. Fig.S17 shows images of the small and large tumors before and after anti-PD-1 therapy.
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- 2023
29. Data from Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma
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Sui Peng, Ming Kuang, Jian Ren, Baogang Peng, Jiaming Lai, Dongming Li, Shaoqiang Li, Shunli Shen, Hong Peng, Qianwen Zeng, Xiaoxue Ren, Jianping Wang, Yuanqi Wang, Changyi Liao, Lijuan Liu, Minghui He, Huanjing Hu, Yuhong Cai, Yubin Xie, and Shuling Chen
- Abstract
Purpose:Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma (ICC). However, little is known about the intertumor heterogeneity (ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making.Experimental Design:We obtained 66 tumor samples from 16 patients with multifocal ICC and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA sequencing, methylation microarray, and multiplex immunostaining. Patients were divided into high- or low-ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed.Results:Multifocal ICC presented considerable intertumor genomic, transcriptional, and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor–immune cell interactions, and upregulated IFN-signature expression in high-immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression.Conclusions:There is comprehensive heterogeneity in the genome, transcriptome, and epigenome of multifocal ICC. On the basis of the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.
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- 2023
30. Supplementary Data from Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma
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Sui Peng, Ming Kuang, Jian Ren, Baogang Peng, Jiaming Lai, Dongming Li, Shaoqiang Li, Shunli Shen, Hong Peng, Qianwen Zeng, Xiaoxue Ren, Jianping Wang, Yuanqi Wang, Changyi Liao, Lijuan Liu, Minghui He, Huanjing Hu, Yuhong Cai, Yubin Xie, and Shuling Chen
- Abstract
Supplementary Data from Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma
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- 2023
31. Table S1, Table S2, Table S4, Table S8, Table S10, Table S11 from The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas
- Author
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Sui Peng, Lixia Xu, Ming Kuang, Jun Yu, Lijian Liang, Baogang Peng, Dongming Li, Lujing Fang, Han Xiao, Xiaoxing Li, Yubin Xie, Shunli Shen, Heping Li, Yu Guo, Minghui He, and Manling Huang
- Abstract
Table S1 shows clinicopathologic information of 12 multifocal HCC patients. Table S2 shows PCR primers used for validation of HBV integration sites. Table S4 shows HBV integration analysis in HCC patients with WGS data. Table S8 shows P-value of pathways enrichment analysis in the small and large tumors of 12 multifocal HCC patients. Table S10 shows correlation between the number of rearrangements and immune activity. Table S11 shows detailed clinical data of eight patients with anti-PD-1 therapy.
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- 2023
32. Data from The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas
- Author
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Sui Peng, Lixia Xu, Ming Kuang, Jun Yu, Lijian Liang, Baogang Peng, Dongming Li, Lujing Fang, Han Xiao, Xiaoxing Li, Yubin Xie, Shunli Shen, Heping Li, Yu Guo, Minghui He, and Manling Huang
- Abstract
Purpose:Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms.Experimental Design:We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti–programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated.Results:The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti–PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti–PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma.Conclusions:The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti–PD-1 therapy.
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- 2023
33. Superhydrophilic three-dimensional porous spent coffee ground reduced palladium nanoparticles for efficient catalytic reduction
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Shaokai Zhang, Guangxue Chen, Minghui He, Zhaohui Yu, Junfei Tian, Huifang Chan, Xiao-Fang Wan, Congcan Shi, Zhangxiong Wu, and Shenghong Sun
- Subjects
Materials science ,Water transport ,Metal Nanoparticles ,Selective catalytic reduction ,Hydrogen Peroxide ,Coffee ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Catalysis ,Nanocellulose ,Biomaterials ,Colloid and Surface Chemistry ,Chemical engineering ,Superhydrophilicity ,Water treatment ,Chemical stability ,Porosity ,Palladium - Abstract
The use of functional biodegradable wastes to treat environmental problems would create minimal extra burden to our environment. In this paper, we propose a sustainable and practical strategy to turn spent coffee ground (SCG) into a multifunctional palladium-loaded catalyst for water treatment instead of going into landfill as solid waste. Bleached delignified coffee ground (D-SCG) has a porous structure and a good capability to reduce Pd (II) to Pd (0). A large amount of nanocellulose is formed on the surface of SCG after bleaching by H2O2, which anchors and disperses the palladium nanoparticles (Pd NPs). The D-SCG loaded with Pd NPs (Pd-D-SCG) is superhydrophilic, which facilitates water transport and thus promotes efficient removal of organic pollutants dissolved in water. Pd-D-SCG exhibits excellent room temperature catalytic activity for the removal of 4-nitrophenol (4-NP) and methylene blue (MB) in water and shows good chemical stability and recyclability in water, with no obvious decrease even after five repeated cycles.
- Published
- 2022
34. Mechanistic insight of SARS-CoV-2 infection using human hepatobiliary organoids
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Yi Zhao, Xiaoxue Ren, Jing Lu, Minghui He, Zhe Liu, Lina Yi, Mingle Huang, Ming Kuang, Haipeng Xiao, Joseph JY Sung, Xiaoxing Li, Lixia Xu, and Jun Yu
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Gastroenterology - Published
- 2022
35. 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
- Subjects
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
36. Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation
- Author
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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
- Subjects
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
37. Research on the Formulation of Rural Planning from the Perspective of Integration of Agriculture, Culture and Tourism: A Case Study of Guifengshan Village, Macheng City, Hubei Province
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Rui Wang, Hong Xu, Xuecheng Hou, and Minghui He
- Subjects
Geography ,Agriculture ,business.industry ,Perspective (graphical) ,Regional science ,business ,Tourism - Abstract
With the gradual construction of the land and space planning system and the acceleration of the urban-rural integrated development process, China’s rural land planning and preparation have ushered in substantial innovations, and at the same time, they are also facing huge challenges. Among them, the low utilization rate of rural land and cultural desertification are the crux of the lagging rural development. This paper takes Guifengshan Village in Macheng City, Hubei Province as an example. Through the analysis of the current advantages of the village, the analysis of challenges, and the evaluation of the suitability of land use, this paper proposes to promote the mutual benefit of agriculture, culture and tourism, and promote the revitalization of Guifengshan Village, forming a “agricultural industry + characteristic cultural creation + red ecology”. “Tourism” jointly develops rural planning strategies. It aims to link rural agriculture, tourism and cultural industries closely on the basis of people-oriented and ecological protection, with income generation as the goal of rural revitalization, to achieve the establishment and extension of the industrial chain, and to promote rural revitalization.
- Published
- 2021
38. N6-Methylandenosine-Related lncRNAs Predict Prognosis and Immunotherapy Response in Bladder Cancer
- Author
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Jianwen Zeng, Yuying Zhang, Chonghe Jiang, Weidong Ji, Baoyi Zhu, Yi Cai, Xiaoling Ying, and Minghui He
- Subjects
Cancer Research ,medicine.medical_treatment ,Cell ,Biology ,medicine.disease_cause ,immune response ,lncRNA ,Immune system ,medicine ,tumor microenvironment ,RC254-282 ,Original Research ,Tumor microenvironment ,Bladder cancer ,N6-methyladenosine ,Competing endogenous RNA ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,Cell cycle ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Cancer research ,bladder cancer ,prognosis ,Carcinogenesis - 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.
- Published
- 2021
39. Relationship between cumulative exposure to metal mixtures and heart rate among Chinese preschoolers
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Ye Fu, Yun Liu, Yanli Liu, Yan Wang, Meiqin Zhu, Wei Lin, Mingzhu Li, Yang Liu, Minghui He, Lili Yu, and Jing Wang
- Subjects
China ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,General Medicine ,General Chemistry ,Pollution ,Arsenic ,Zinc ,Heart Rate ,Metals, Heavy ,Humans ,Environmental Chemistry ,Child - Abstract
The cumulative exposure to metals affects cardiac conduction, and the effect of polymetallic exposure on heart rate in children is unknown. To evaluate the relationship between cumulative exposure to metal mixtures and heart rate among Chinese preschoolers, the determination of urinary 24 metals was processed by high-resolution inductively coupled plasma-mass spectrometry. Heart rate was recorded when measuring blood pressure after resting 5 min or longer. As a method to compute the Environmental risk score (ERS) according to heart rate under heavy metal mixtures, adaptive elastic net (AENET) with 299 predictors which were formed by the combination of main effects, squared terms, and pairwise interactions of heavy metals with a total number of 23, 23, 253 respectively. To further assess the associations between ERS and heart rate, regression analyses were performed with complex survey designs. The construction of ERS under heart rate-related metal mixtures was returned by AENET in according to 11 main effects (tin, arsenic, zinc, iron, titanium, vanadium, nickel, manganese, cobalt, copper and chromium) and 2 squared terms (tungsten and rubidium). A high correlation was monitored between the alteration of ERS in the study population and heart rate (β = 1.030, 95% CI: 0.730 - 1.330 in 1239; β = 1.085, 95% CI: 0.777 - 1.393 in 1061). Significant associations of ERS with higher heart rates were also pointed out (Ps 0.05). Our study elucidates the association of the cumulative exposure of heavy metals as mixtures and heart rate among Chinese preschoolers. Further research is obliged to corroborate these findings in longitudinal studies.
- Published
- 2022
40. Preparation of high-density garnet thin sheet electrolytes for all-solid-state Li-Metal batteries by tape-casting technique
- Author
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Yi-Peng Zhang, Kang-Ning Gao, Zhonghui Cui, Xixiang Li, Jun Gao, Minghui He, Yiqiu Li, Tao Zhang, and Zhongliang Zhan
- Subjects
Tape casting ,Materials science ,Mechanical Engineering ,Metals and Alloys ,Sintering ,02 engineering and technology ,Electrolyte ,Thin sheet ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Electrochemistry ,01 natural sciences ,0104 chemical sciences ,Metal ,Mechanics of Materials ,visual_art ,Materials Chemistry ,visual_art.visual_art_medium ,Relative density ,Ionic conductivity ,Composite material ,0210 nano-technology - Abstract
Garnet electrolyte is a promising candidate for the development of all-solid-state Li-metal batteries, because of its safety and stability against Li metal. However, its practical application is limited by the difficulty in production of its high-density thin sheet. In this work, we have fabricated garnet thin sheet electrolytes (Li6.4La3Zr1.4Ta0.6O12, LLZTO) by tape-casting technique. By using Li2O as a liquid-phase sintering additive, a high relative density up to 99% was achieved. Electrochemical results show the LLZTO sheets have an ionic conductivity of 5.2 × 10−4 S cm−1 at 30 °C and good cycling stability against Li metal. Based on the sheets, all-solid-state Li/LLZTO/LiFePO4 batteries exhibit excellent reversible cycles at 60 °C and 0.1C with an initial discharge specific capacity of 125.8 mA h g−1 and a retention of 92.3% after 50 cycles. These results indicate that the tape-casting process demonstrated here provides an effective method of producing high-density garnet thin sheet electrolytes for high-performance all-solid-state Li-metal batteries.
- Published
- 2019
41. Nanocomposite intermediate layers formed by conversion reaction of SnO2 for Li/garnet/Li cycle stability
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Jingming Fu, Xiangxin Guo, Hanyu Huo, Yiqi Li, Fangfang Xu, Minghui He, Yue Chen, Tao Zhang, and Ning Zhao
- Subjects
Chemical substance ,Materials science ,Nanocomposite ,Renewable Energy, Sustainability and the Environment ,Alloy ,Energy Engineering and Power Technology ,02 engineering and technology ,Electrolyte ,engineering.material ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,law.invention ,Magazine ,Chemical engineering ,Coating ,law ,Fast ion conductor ,engineering ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,0210 nano-technology ,Science, technology and society - Abstract
Garnets are promising solid electrolytes for developing solid state Li batteries, owing to their features of relatively high conductivity and stability against lithium metal. However, they show shortcoming of Li penetration through garnets during Li plating and stripping, which limits their practice application. Herein, we present a strategy to solve such problem by coating SnO2 films on the surfaces of the Li6·4La3Zr1·4Ta0·6O12 pellets. Through conversion reaction of SnO2 with Li at 200 °C, the nanocomposite layers consisting of crosslinked LixSn and Li2O are formed between the Li and the Li6·4La3Zr1·4Ta0·6O12 electrolytes. This leads to transition from lithiophobicity to lithiophilicity, thus greatly reducing interfacial resistance from 1100 Ω cm2 to 25 Ω cm2. Furthermore, taking advantage of suppressing volume change of LixSn alloy which is about 260%, the intermediate layers maintain integrity under the current densities of 0.2 mA cm−2 for 650 h cycles. In addition, the critical current density of Li/SnO2-Li6.4La3Zr1·4Ta0·6O12-SnO2/Li can be as high as 1.15 mA cm−2. As a proof-of-concept, this effective interface modification based on conversion reaction method contributes to a useful way of solving the Li/garnet interface problem and promoting the solid state Li batteries development.
- Published
- 2019
42. Multiomic Analysis Reveals Comprehensive Tumor Heterogeneity and Distinct Immune Subtypes in Multifocal Intrahepatic Cholangiocarcinoma
- Author
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Jianping Wang, Baogang Peng, Yubin Xie, Yuanqi Wang, Yuhong Cai, Hong Peng, Shao-Qiang Li, Minghui He, Shuling Chen, Shunli Shen, Changyi Liao, Xiaoxue Ren, Lijuan Liu, Dongming Li, Huanjing Hu, Ming Kuang, Jiaming Lai, Sui Peng, Jian Ren, and Qianwen Zeng
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Epigenome ,Immunotherapy ,Prognosis ,Targeted therapy ,Transcriptome ,Cholangiocarcinoma ,Immune system ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Internal medicine ,Exome Sequencing ,medicine ,Biomarkers, Tumor ,Humans ,business ,Immunostaining ,Intrahepatic Cholangiocarcinoma ,Epigenomics - Abstract
Purpose: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma (ICC). However, little is known about the intertumor heterogeneity (ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making. Experimental Design: We obtained 66 tumor samples from 16 patients with multifocal ICC and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA sequencing, methylation microarray, and multiplex immunostaining. Patients were divided into high- or low-ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed. Results: Multifocal ICC presented considerable intertumor genomic, transcriptional, and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor–immune cell interactions, and upregulated IFN-signature expression in high-immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression. Conclusions: There is comprehensive heterogeneity in the genome, transcriptome, and epigenome of multifocal ICC. On the basis of the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.
- Published
- 2021
43. Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells
- Author
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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
- Subjects
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
44. β-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus
- Author
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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
- Subjects
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.
- Published
- 2020
45. The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas
- Author
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Ming Kuang, Heping Li, Dongming Li, Baogang Peng, Minghui He, Lijian Liang, Shunli Shen, Yu Guo, Sui Peng, Lixia Xu, Lujing Fang, Han Xiao, Xiaoxing Li, Manling Huang, Jun Yu, and Yubin Xie
- Subjects
0301 basic medicine ,Adult ,Male ,Cancer Research ,Programmed cell death ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,CD8-Positive T-Lymphocytes ,03 medical and health sciences ,Genetic Heterogeneity ,0302 clinical medicine ,Immune system ,Lymphocytes, Tumor-Infiltrating ,Downregulation and upregulation ,Interferon ,Tumor-Associated Macrophages ,Biomarkers, Tumor ,Tumor Microenvironment ,Medicine ,Hepatectomy ,Humans ,RNA-Seq ,Immune Checkpoint Inhibitors ,Aged ,Whole Genome Sequencing ,business.industry ,Liver Neoplasms ,Immunotherapy ,Middle Aged ,medicine.disease ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,Liver ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Mutation ,Cancer research ,Immunohistochemistry ,Female ,business ,CD8 ,medicine.drug ,Follow-Up Studies - Abstract
Purpose: Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms. Experimental Design: We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti–programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated. Results: The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti–PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti–PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma. Conclusions: The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti–PD-1 therapy.
- Published
- 2019
46. IMPROVED ARTIFICIAL NEURAL NETWORK BASED ON INTELLIGENT OPTIMIZATION ALGORITHM
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Minghui He and Yi Xu
- Subjects
0209 industrial biotechnology ,Artificial neural network ,Optimization algorithm ,Computer science ,business.industry ,General Neuroscience ,02 engineering and technology ,020901 industrial engineering & automation ,Artificial Intelligence ,Hardware and Architecture ,0202 electrical engineering, electronic engineering, information engineering ,020201 artificial intelligence & image processing ,Artificial intelligence ,business ,Software - Published
- 2018
47. Graphene-assisted construction of electrocatalysts for carbon dioxide reduction
- Author
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Yugang Huang, Hong Zhao, Yinlei Lin, Yuyuan Zhang, Huawen Hu, Dongchu Chen, Jian Zhen Ou, Minghui He, Xuejun Xu, and Lifang Deng
- Subjects
Materials science ,Graphene ,General Chemical Engineering ,chemistry.chemical_element ,Nanotechnology ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Electrochemistry ,01 natural sciences ,Redox ,Industrial and Manufacturing Engineering ,0104 chemical sciences ,law.invention ,Catalysis ,Reaction rate ,chemistry ,law ,Specific surface area ,Environmental Chemistry ,0210 nano-technology ,Carbon ,Electrochemical reduction of carbon dioxide - Abstract
The electrochemical conversion of the greenhouse gas, carbon dioxide (CO2), to energy fuels and value-added chemicals presents one of the most valuable approaches to harvest pollutants and produce renewable energy. However, the stable molecular structure of CO2 and the sluggish reaction kinetics make CO2 reduction reaction (CO2RR) formidably challenging to achieve reaction rate and selectivity practical in industry. Graphene and its derivatives have been considered a group of intriguing materials to develop advanced CO2RR electrocatalysts due to their large specific surface area, remarkable electron transfer ability, superior stability, and easy tunability of the structure and surface properties. Herein, we comprehensively discuss the state-of-the-art electrocatalysts constructed with graphene and derivatives for active and selective CO2RR within the recent five years, mainly including the electrocatalysts with both metal-based (e.g., noble, non-noble, or combined thereof) and non-metal (e.g., doped, modified, defected, or composited) catalytic sites. To present the versatile, high-performance metal-based CO2RR electrocatalysts constructed with graphene, we further subdivide them according to the sizes, oxidation states, metal species synergies, dimensionalities, and versatility. Finally, we provide the challenges and perspectives in this emerging area of utilising CO2 to produce various carbon-based fuels and chemicals via graphene chemistry.
- Published
- 2021
48. 3D printing of ultra-tough, self-healing transparent conductive elastomeric sensors
- Author
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Guangxue Chen, Minghui He, Bin Su, and Ling Cai
- Subjects
Materials science ,business.industry ,General Chemical Engineering ,Soft robotics ,3D printing ,Nanotechnology ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Elastomer ,01 natural sciences ,Industrial and Manufacturing Engineering ,0104 chemical sciences ,chemistry.chemical_compound ,Photopolymer ,Polymerization ,chemistry ,Self-healing ,Environmental Chemistry ,Electronics ,0210 nano-technology ,business ,Choline chloride - Abstract
Ultra-tough transparent conductive elastomers (TCEs) with self-healing performance are of great significance for research in the fields of soft robotics, optical display electronics, wearable electronic equipment and human–computer interaction. However, their limitation, such as the desolventizing process, low polymerization rate or balance between toughness and self-healing performance, cause difficulty in manufacturing by the 3D printing technique. Here, we propose a novel preparation strategy for 3D printed TCEs based on the photopolymerization of maleic acid (MA)/choline chloride (ChCl) and acrylamide (AAm)/choline chloride type polymerizable deep eutectic solvents (PDESs). PDES can polymerize into a tough and rich in hydrogen bonds poly(PDES) in a few seconds without solvent evaporation. The printed TCEs with precision of 10 µm have high transparency (95.6%) and stable electrical signals at 50% compression for 10,000 cycles. In addition, efficient self-healing performance due to the dynamic hydrogen bonds of poly(PDES) provides broad application prospects for 3D printed TCEs in long-term pressure-resistant intelligent applications.
- Published
- 2021
49. Research on site selection of old campus bookstore based on the combination of space syntax and analytic hierarchy process——Take Huangjiahu Campus of Wuhan University of Science and Technology as an example
- Author
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Hong Xu, Rui Wang, Minghui He, JianJun Chen, SiWei Liu, and TianYue Li
- Subjects
World Wide Web ,Computer science ,Site selection ,Analytic hierarchy process ,ComputingMilieux_MISCELLANEOUS ,Space syntax - Abstract
The bookstore is an integral part of campus public service, and it is an essential place for reading, learning and spending for teachers and students. Provided the current management and development problems faced by old campus bookstores, this article takes the old campus bookstore in the Huangjiahu campus of Wuhan University of Science and Technology as a research case while uses space syntax theory, Depthmap software, and axis models to analyzes and evaluate accessibility, and then optimize campus old location and layout of bookstores. Simultaneously, by using the analytic hierarchy process, the simulated bookstore sites of selection in the campus are tested at the target level, decision level and plan level. This article aims to propose optimization methods for the management and development of old campus bookstores from the perspective of spatial location selection through qualitative quantification and provide constructive references for similar research.
- Published
- 2021
50. Phototriggered base proliferation: a powerful 365 nm LED photoclick tool for nucleophile-initiated thiol-Michael addition reaction
- Author
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Xiaoyuan Guan, Minghui He, Ruixin Xu, and Jianwen Yang
- Subjects
chemistry.chemical_classification ,Addition reaction ,Base (chemistry) ,General Chemical Engineering ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Photochemistry ,01 natural sciences ,0104 chemical sciences ,Reaction rate ,chemistry ,Photosensitivity ,Nucleophile ,Michael reaction ,Thiol ,Amine gas treating ,0210 nano-technology - Abstract
Photocaged amines (PCAs) can allow a spatiotemporal control of the highly versatile and widely implemented nucleophile-catalyzed thiol-Michael addition reaction. However, a major challenge with most PCAs is that their relatively low quantum yields easily lead to low photosensitivity, especially under the radiation of light-emitting diodes (LEDs). In this paper, the phototriggered base proliferation (PBP) reaction as a powerful 365 nm LED photoclick tool is presented for the nucleophile-initiated thiol-Michael addition reaction. Compared to the PCA system, the advantages of this approach lie in its enhanced photosensitivity, increased reaction rate and elevated conversion. Finally, due to the persistent interactions of the produced longeval amine, remarkable post conversion was thus initially achieved after irradiation.
- Published
- 2017
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