Publications by authors named "Quan Gu"

63 Publications

Modified recombinant human IgG1-Fc is superior to natural intravenous immunoglobulin at inhibiting immune-mediated demyelination.

Immunology 2021 Apr 20. Epub 2021 Apr 20.

Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.

Intravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Although Fc fragments derived from IVIG have shown efficacy in controlling immune thrombocytopenia in children, the mechanisms of action are unclear and controversial. The aim of this study was to dissect IVIG effector mechanisms using further adapted Fc fragments on demyelination in an ex vivo model of the central nervous system-immune interface. Using organotypic cerebellar slice cultures (OSCs) from transgenic mice, we induced extensive immune-mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement. Protective effects of adapted Fc fragments were assessed by live imaging of green fluorescent protein expression, immunohistochemistry and confocal microscopy. Cysteine- and glycan-adapted Fc fragments protected OSC from demyelination in a dose-dependent manner where equimolar concentrations of either IVIG or control Fc were ineffective. The protective effects of the adapted Fc fragments are partly attributed to interference with complement-mediated oligodendroglia damage. Transcriptome analysis ruled out signatures associated with inflammatory or innate immune responses. Taken together, our findings show that recombinant biomimetics can be made that are at least two hundred-fold more effective than IVIG in controlling demyelination by anti-MOG antibodies.
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http://dx.doi.org/10.1111/imm.13341DOI Listing
April 2021

Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling.

Viruses 2021 Jan 19;13(1). Epub 2021 Jan 19.

Unité des Stratégies Antivirales, Institut Pasteur, 75015 Paris, France.

Rodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases in humans. Although an exacerbated immune response relates to hantaviral pathologies, orthohantaviruses have to antagonize the antiviral interferon (IFN) response to successfully propagate in infected cells. We studied interactions of structural and nonstructural (NSs) proteins of pathogenic Puumala (PUUV), low-pathogenic Tula (TULV), and non-pathogenic Prospect Hill (PHV) viruses, with human type I and III IFN (IFN-I and IFN-III) pathways. The NSs proteins of all three viruses inhibited the RIG-I-activated IFNβ promoter, while only the glycoprotein precursor (GPC) of PUUV, or its cleavage product Gn/Gc, and the nucleocapsid (N) of TULV inhibited it. Moreover, the GPC of both PUUV and TULV antagonized the promoter of IFN-stimulated responsive elements (ISRE). Different viral proteins could thus contribute to inhibition of IFNβ response in a viral context. While PUUV and TULV strains replicated similarly, whether expressing entire or truncated NSs proteins, only PUUV encoding a wild type NSs protein led to late IFN expression and activation of IFN-stimulated genes (ISG). This, together with the identification of particular domains of NSs proteins and different biological processes that are associated with cellular proteins in complex with NSs proteins, suggested that the activation of IFN-I is probably not the only antiviral pathway to be counteracted by orthohantaviruses and that NSs proteins could have multiple inhibitory functions.
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http://dx.doi.org/10.3390/v13010140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835746PMC
January 2021

Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures.

Viruses 2021 Jan 11;13(1). Epub 2021 Jan 11.

MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK.

Understanding how Zika virus (; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination-which is critical for saltatory conduction and neuronal function-has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.
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http://dx.doi.org/10.3390/v13010091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827345PMC
January 2021

BingleSeq: a user-friendly R package for bulk and single-cell RNA-Seq data analysis.

PeerJ 2020 22;8:e10469. Epub 2020 Dec 22.

MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.

Background: RNA sequencing is an indispensable research tool used in a broad range of transcriptome analysis studies. The most common application of RNA Sequencing is differential expression analysis and it is used to determine genetic loci with distinct expression across different conditions. An emerging field called single-cell RNA sequencing is used for transcriptome profiling at the individual cell level. The standard protocols for both of these approaches include the processing of sequencing libraries and result in the generation of count matrices. An obstacle to these analyses and the acquisition of meaningful results is that they require programing expertise. Although some effort has been directed toward the development of user-friendly RNA-Seq analysis analysis tools, few have the flexibility to explore both Bulk and single-cell RNA sequencing.

Implementation: BingleSeq was developed as an intuitive application that provides a user-friendly solution for the analysis of count matrices produced by both Bulk and Single-cell RNA-Seq experiments. This was achieved by building an interactive dashboard-like user interface which incorporates three state-of-the-art software packages for each type of the aforementioned analyses. Furthermore, BingleSeq includes additional features such as visualization techniques, extensive functional annotation analysis and rank-based consensus for differential gene analysis results. As a result, BingleSeq puts some of the best reviewed and most widely used packages and tools for RNA-Seq analyses at the fingertips of biologists with no programing experience.

Availability: BingleSeq is as an easy-to-install R package available on GitHub at https://github.com/dbdimitrov/BingleSeq/.
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http://dx.doi.org/10.7717/peerj.10469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761193PMC
December 2020

[MiR-4443 promotes migration and invasion of breast cancer cells by inhibiting PEBP1 expression].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Dec;40(12):1712-1719

Department of Oncology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China.

Objective: To investigate the effect of miR-4443 expression on migration and invasion of breast cancer.

Methods: We examined the expression of miR-4443 in breast carcinoma in situ and paired adjacent tissues from 3 breast cancer patients with high-throughput sequencing and verified the results using TCGA database. We also detected miR-4443 expressions using real-time quantitative PCR (RT-qPCR) in low invasive and highly invasive breast cancer cells (MCF-7 and MDA-MB-231 cells, respectively). The changes in apoptosis, migration and invasion of MCF-7 and MDA-MB-231 cells after transfection with miR-4443 mimics, mimics-NC, miR-4443 inhibitor or inhibitor-NC were analyzed using flow cytometry, wound healing assay and Transwell invasion assay. The target gene of miR-4443 was predicted by bioinformatics software and validated by a dual luciferase reporter gene system. RT-qPCR and Western blotting were performed to detect the expression of recombinant human phosphatidyl ethanolamine binding protein 1 (PEBP1) in the transfected cells.

Results: The expression of miR-4443 was significantly higher in the breast cancer tissues than in the adjacent tissues ( < 0.01), and was significantly up-regulated in MDA-MB-231 cells as compared with MCF-7 cells ( < 0.01). Transfection with miR-4443 mimics or inhibitors did not obviously affect apoptosis rate of the breast cancer cells (>0.05), but significantly enhanced or weakened the migration and invasion abilities of the cells, respectively ( < 0.01). Bioinformatic analysis identified PEBP1 as the target gene of miR-4443 with a close correlation with metastasis of breast cancer ( < 0.01), and the result was confirmed by double luciferase reporter gene assay. The mRNA and protein expression of PEBP1 were significantly lower in MDA-MB-231 cells than in MCF-7 cells ( < 0.01), and miR-4443 over-expression or knockdown significantly down-regulated or up-regulated PEBP1 expressions in the cells, respectively ( < 0.01).

Conclusions: MiR-4443 promotes the migration and invasion of breast cancer cells by inhibiting the expression of PEBP1, suggesting the possibility of suppressing miR-4443 expression as a potential therapeutic strategy for breast cancer.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.12.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835697PMC
December 2020

Exosome EpCAM promotes the metastasis of glioma by targeting the CD44 signaling molecule on the surface of glioma cells.

Adv Clin Exp Med 2020 Nov;29(11):1277-1282

Department of Neurosurgery, Fudan University Affiliated Zhongshan Hospital Qingpu Branch, Shanghai, China.

Background: Glioma, the most common primary tumor in the central nervous system, originates from glial cells and has a poor prognosis.

Objectives: This experimental laboratory study was designed to explore the role of epithelial cell adhesion molecule (EpCAM) in the metastasis of glioma.

Material And Methods: Serum samples were collected from patients with non-metastatic or metastatic glioma (n = 20 per group), and healthy volunteers (n = 8). Exosomes were isolated from the serum and the morphological characteristics were observed under a scanning electron microscope (SEM). The expression of CD81 and CD63 was measured to identify exosomes. Glioma tissue and the adjacent normal tissue samples were obtained from patients with non-metastatic or metastatic glioma (n = 12 per group). Meanwhile, 4 normal brain tissue samples were collected. The expression of CD44, hyaluronan-mediated motility receptor (HMMR), and matrix metalloproteinase-9 (MMP-9) was determined in each group using immunohistochemistry. The protein expression of CD44, HMMR, matrix metalloproteinase-2 (MMP-2), MMP-9, and selectin E (SELE) was measured with western blotting.

Results: Exosomes were present in the serum, and the proteins CD81 and CD63 were expressed in all 3 groups. CD44 was highly expressed in the non-metastasis and metastasis groups. The expression of HMMR and MMP-9 in the Adj-metastasis and Adj-non-metastasis groups was high, while in the other groups, the levels were low. The expression of CD44 in the metastasis and non-metastasis groups was significantly higher than that of the negative control (NC) group, and the expression in the metastasis group was higher than that of the non-metastasis group. The MMP-2 and MMP-9 were not found in either the metastasis or non-metastasis group. The protein expression of HMMR and SELE was high in all groups.

Conclusions: Exosome EpCAM promoted the metastasis of glioma by targeting CD44.
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http://dx.doi.org/10.17219/acem/126051DOI Listing
November 2020

Intensity-noise suppression in 1950-nm single-frequency fiber laser by bidirectional amplifier configuration.

Opt Lett 2020 Oct;45(19):5484-5487

In this Letter, a bidirectional amplifier configuration suppressing the relative intensity noise in a 1950-nm linearly polarized single-frequency fiber laser (SFFL) is proposed. The scheme to amplify the signal in a nonlinear saturated amplification regime with low gain distribution for suppressing the RIN is theoretically analyzed. By optimizing the input power level and reflectivity of the bidirectional power-amplifier, the RIN is decreased maximally by >24 within the frequency range of 200 kHz. A stable output power of over 5.16 W with a polarization extinction ratio of 21.2 dB is obtained. Additionally, the amplified signal maintains a linewidth of 7.1 kHz nearly identical with that of the seed, both with a signal-to-noise ratio of more than 60 dB. This all-optical technique on noise suppression applied to the fiber amplifier paves the way to realize low-noise SFFL with power improvement.
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http://dx.doi.org/10.1364/OL.402590DOI Listing
October 2020

tagHi-C Reveals 3D Chromatin Architecture Dynamics during Mouse Hematopoiesis.

Cell Rep 2020 09;32(13):108206

State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences, Tianjin, China; National Clinical Research Center for Blood Diseases, Tianjin, China; Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China; Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China; Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China. Electronic address:

Spatiotemporal chromatin reorganization during hematopoietic differentiation has not been comprehensively characterized, mainly because of the large numbers of starting cells required for current chromatin conformation capture approaches. Here, we introduce a low-input tagmentation-based Hi-C (tagHi-C) method to capture the chromatin structures of hundreds of cells. Using tagHi-C, we are able to map the spatiotemporal dynamics of chromatin structure in ten primary hematopoietic stem, progenitor, and differentiated cell populations from mouse bone marrow. Our results reveal that changes in compartment dynamics and the Rabl configuration occur during hematopoietic cell differentiation. We identify gene-body-associating domains (GADs) as general structures for highly expressed genes. Moreover, we extend the body of knowledge regarding genes influenced by genome-wide association study (GWAS) loci through spatial chromatin looping. Our study provides the tagHi-C method for studying the three-dimensional (3D) genome of a small number of cells and maps the comprehensive 3D chromatin landscape of bone marrow hematopoietic cells.
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http://dx.doi.org/10.1016/j.celrep.2020.108206DOI Listing
September 2020

Human Cytomegalovirus Long Non-coding RNA1.2 Suppresses Extracellular Release of the Pro-inflammatory Cytokine IL-6 by Blocking NF-κB Activation.

Front Cell Infect Microbiol 2020 22;10:361. Epub 2020 Jul 22.

MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.

Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 h after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of MCP-1 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signaling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-κB-dependent cytokine and chemokine release during HCMV infection, thereby impacting downstream immune responses.
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http://dx.doi.org/10.3389/fcimb.2020.00361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387431PMC
July 2020

The biological function of m6A demethylase ALKBH5 and its role in human disease.

Cancer Cell Int 2020 28;20:347. Epub 2020 Jul 28.

Department of Oncology, Nanjing Jiangning Hospital, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 210000 China.

Human AlkB homolog H5 (ALKBH5) is a primary m6A demethylase, which is dysregulated and acts as a biological and pharmacological role in human cancers or non-cancers. ALKBH5 plays a dual role in various cancers through regulating kinds of biological processes, such as proliferation, migration, invasion, metastasis and tumor growth. In addition, it takes a great part in human non-cancer, including reproductive system diseases. The underlying regulatory mechanisms of ALKBH5 that relys on m6A-dependent modification are implicated with long non-coding RNA, cancer stem cell, autophagy and hypoxia. ALKBH5 is also an independent prognostic indicator in various cancers. In this review, we summarized the current evidence on ALKBH5 in diverse human cancers or non-cancers and its potential as a prognostic target.
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http://dx.doi.org/10.1186/s12935-020-01450-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388453PMC
July 2020

Transcriptome analysis provides insights into the molecular bases in response to different nitrogen forms-induced oxidative stress in tea plant roots (Camellia sinensis).

Funct Plant Biol 2020 11;47(12):1073-1082

State Key Laboratory of Tea Plant Biology and Utilisation, Anhui Agricultural University, Hefei 230036, China.

Previous studies have suggested that the maintenance of redox homeostasis is essential for plant growth. Here we investigated how redox homeostasis and signalling is modulated in response to different nitrogen (N) forms in tea plant roots. Our results showed that both N deficiency and nitrate (NO3-) can trigger the production of hydrogen peroxide and lipid peroxidation in roots. In contrast, these responses were not altered by NH4+. Further, N deficiency and NO3--triggered redox imbalance was re-established by increased of proanthocyanidins (PAs) and glutathione (GSH), as well as upregulation of representative antioxidant enzyme activities and genes. To further explore the molecular bases of these responses, comparative transcriptome analysis was performed, and redox homeostasis-associated differentially expressed genes (DEGs) were selected for bioinformatics analysis. Most of these genes were involved in the flavonoid biosynthesis, GSH metabolism and the antioxidant system, which was specifically altered by N deficiency or NO3-. Moreover, the interplay between H2O2 (generated by RBOH and Ndufab1) and hormones (including abscisic acid, auxin, cytokinin and ethylene) in response to different N forms was suggested. Collectively, the above findings contribute to an understanding of the underlying molecular mechanisms of redox homeostasis and signalling in alleviating oxidative stress in tea plant roots.
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http://dx.doi.org/10.1071/FP20093DOI Listing
November 2020

Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.

Cell 2020 06 18;181(7):1502-1517.e23. Epub 2020 Jun 18.

MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.

RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 5'-m7G-capped host transcripts to prime viral mRNA synthesis ("cap-snatching"). We hypothesized that start codons within cap-snatched host transcripts could generate chimeric human-viral mRNAs with coding potential. We report the existence of this mechanism of gene origination, which we named "start-snatching." Depending on the reading frame, start-snatching allows the translation of host and viral "untranslated regions" (UTRs) to create N-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting. We show that both types of chimeric proteins are made in IAV-infected cells, generate T cell responses, and contribute to virulence. Our results indicate that during infection with IAV, and likely a multitude of other human, animal and plant viruses, a host-dependent mechanism allows the genesis of hybrid genes.
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http://dx.doi.org/10.1016/j.cell.2020.05.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323901PMC
June 2020

55  W  kilohertz-linewidth core- and in-band-pumped linearly polarized single-frequency fiber laser at 1950  nm.

Opt Lett 2020 Apr;45(8):2343-2346

Based on core- and in-band-pumped polarization-maintaining ${{\rm Tm}^{3 + }}$Tm-doped single-cladding fiber (PM-TSF, the core diameter is 9 µm) by a 1610 nm fiber laser and a distributed Bragg reflector seed laser, a linearly polarized single-frequency fiber laser (LP-SFFL) at 1950 nm with an output power of 55.3 W and a laser linewidth of 6.95 kHz is demonstrated. The output beam qualities of ${M}_x^2$Mx2 and ${ M}_y^2$My2 are measured to be 1.01 and 1.03, respectively. The slope efficiency with respect to the launched pump power is 71.0%, in comparison with a theoretical quantum efficiency of 82.6%. A polarization-extinction ratio of 19 dB and an optical signal-to-noise ratio of 58 dB are obtained from the 1950 nm LP-SFFL. To the best of our knowledge, to date, this is the highest power of 2.0 µm SFFL output directly from a strict single-mode active fiber. Our experiment offers a promising solution to the current limitations of the high-performance fiber lasers at 2.0 µm, which is particularly essential for coherent detection.
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http://dx.doi.org/10.1364/OL.388826DOI Listing
April 2020

Decitabine and all-trans retinoic acid synergistically exhibit cytotoxicity against elderly AML patients via miR-34a/MYCN axis.

Biomed Pharmacother 2020 May 29;125:109878. Epub 2020 Jan 29.

Department of Hematology, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Jiangsu Province, 213003, PR China. Electronic address:

This study aimed to investigate the efficacy and mechanism of decitabine (DAC) and all-trans retinoic acid (ATRA) in elderly acute myeloid leukemia (AML) patients and cultured cells. Our clinical trial enrolled 36 elderly patients who were judged ineligible for conventional chemotherapy, receiving DAC and ATRA regimen (DAC 20 mg/m days 1-5; ATRA 20 mg/m days 4-28 in the first cycle and days 1-28 in the subsequent cycle). Treated with a median of 3 cycles (range 1-6), 44.4 % of patients achieved complete remission (CR), 11.1 % achieved CR with incomplete peripheral count recovery (CRi) and 13.9 % achieved partial remission (PR). The median overall survival (OS) was 12.1 months; the 1-year and 2-year OS rates were 49.6 % and 17.2 %. In addition, our in vitro studies indicated that the antineoplastic activities of DAC and ATRA mutually reinforced, which induced growth inhibition, cell cycle arrest and apoptosis of AML cells. Meanwhile, we found DAC and ATRA inhibited DNMT1, activated miR-34a via promoter hypomethylation, down-regulated its target MYCN and thus exerted a synergistic antineoplastic effect. In conclusion, DAC plus ATRA regimen might be effective and well-tolerated for elderly patients partially through modulating miR-34a/MYCN axis.
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http://dx.doi.org/10.1016/j.biopha.2020.109878DOI Listing
May 2020

Event-based encoding of biological motion and location in visual working memory.

Q J Exp Psychol (Hove) 2020 Aug 7;73(8):1261-1277. Epub 2020 Feb 7.

Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, P.R. China.

We make use of discrete yet meaningful events to orient ourselves to the dynamic environment. Among these events, biological motion, referring to the movements of animate entities, is one of the most biologically salient. We usually encounter biological motions of multiple human beings taking place simultaneously at distinct locations. How we encode biological motions into visual working memory (VWM) to form a coherent experience of the external world and guide our social behaviour remains unclear. This study for the first time addressed the VWM encoding mechanism of biological motions and their corresponding locations. We tested an event-based encoding hypothesis for biological motion and location: When one element of an event is required to be memorised, the irrelevant element of an event will also be extracted into VWM. We presented participants with three biological motions at different locations and required them to memorise only the biological motions or their locations while ignoring the other dimension. We examined the event-based encoding by probing a distracting effect: If the event-based encoding took place, the change of irrelevant dimension in the probe would lead to a significant distraction and impair the performance of detecting target dimension. We found significant distracting effects, which lasted for 3 s but vanished at 6 s, regardless of the target dimension (biological motions vs. locations, Experiment 1) and the exposure time of memory array (1 s vs. 3 s, Experiment 2). These results together support an event-based encoding mechanism during VWM encoding of biological motions and their corresponding locations.
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http://dx.doi.org/10.1177/1747021820903042DOI Listing
August 2020

Agent identity drives adaptive encoding of biological motion into working memory.

J Vis 2019 12;19(14)

Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, People's Republic of China.

To engage in normal social interactions, we have to encode human biological motions (BMs, e.g., walking and jumping), which is one of the most salient and biologically significant types of kinetic information encountered in everyday life, into working memory (WM). Critically, each BM in real life is produced by a distinct person, carrying a dynamic motion signature (i.e., identity). Whether agent identity influences the WM processing of BMs remains unknown. Here, we addressed this question by examining whether memorizing BMs with different identities promoted the WM processing of task-irrelevant clothing colors. Two opposing hypotheses were tested: (a) WM only stores the target action (element-based hypothesis) and (b) WM stores both action and irrelevant clothing color (event-based hypothesis), interpreting each BM as an event. We required participants to memorize actions that either performed by one agent or distinct agents, while ignoring clothing colors. Then we examined whether the irrelevant color was also stored in WM by probing a distracting effect: If the color was extracted into WM, the change of irrelevant color in the probe would lead to a significant distracting effect on action performance. We found that WM encoding of BMs was adaptive: Once the memorized actions had different identities, WM adopted an event-based encoding mode regardless of memory load and probe identity (Experiment 1, different-identity group of Experiment 2, and Experiment 3). However, WM used an element-based encoding mode when memorized-actions shared the same identity (same-identity group of Experiment 2) or were inverted (Experiment 4). Overall, these findings imply that agent identity information has a significant effect on the WM processing of BMs.
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http://dx.doi.org/10.1167/19.14.6DOI Listing
December 2019

Relation Between Working Memory Capacity of Biological Movements and Fluid Intelligence.

Front Psychol 2019 18;10:2313. Epub 2019 Oct 18.

Department of Psychology, Zhejiang University, Hangzhou, China.

Studies have revealed that there is an independent buffer for holding biological movements (BM) in working memory (WM), and this BM-WM has a unique link to our social ability. However, it remains unknown as to whether the BM-WM also correlates to our cognitive abilities, such as fluid intelligence (Gf). Since BM processing has been considered as a hallmark of social cognition, which distinguishes from canonical cognitive abilities in many ways, it has been hypothesized that only canonical object-WM (e.g., memorizing color patches), but not BM-WM, emerges to have an intimate relation with Gf. We tested this prediction by measuring the relationship between WM capacity of BM and Gf. With two Gf measurements, we consistently found moderate correlations between BM-WM capacity, the score of both Raven's advanced progressive matrix (RAPM), and the Cattell culture fair intelligence test (CCFIT). This result revealed, for the first time, a close relation between WM and Gf with a social stimulus, and challenged the double-dissociation hypothesis for distinct functions of different WM buffers.
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http://dx.doi.org/10.3389/fpsyg.2019.02313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842976PMC
October 2019

Sustainable Ligand-Free, Palladium-Catalyzed Suzuki-Miyaura Reactions in Water: Insights into the Role of Base.

ChemSusChem 2019 Nov 14. Epub 2019 Nov 14.

Key Laboratory of Applied Surface and Colloid Chemistry MOE, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710119, P. R. China.

A simple and efficient system was developed for the ligand-free Pd-catalyzed Suzuki-Miyaura reaction in water under mild conditions. Quaternary ammonium hydroxides with long chains were found to be very suitable bases. This ligand-free Pd-catalyzed Suzuki-Miyaura reaction showed improved durability in water with Pd loadings decreased to ppm level. Bases were shown to stabilize active palladium species in addition to acting as a base during the catalytic process. In the catalytic system with a strong base, the soluble active Pd ion exhibited anti-reduction properties, which prevented aggregation and deactivation of Pd species. The entire catalytic system could be recycled after separating the product by simple filtration. The water-compatible and air-stable effective catalytic protocol described herein represents an attractive and green synthetic advance in Suzuki-Miyaura couplings.
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http://dx.doi.org/10.1002/cssc.201902853DOI Listing
November 2019

Sn-Triggered Two-Dimensional Fast Protein Assembly with Emergent Functions.

ACS Nano 2019 07 20;13(7):7736-7749. Epub 2019 Jun 20.

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering , Shaanxi Normal University , Xi'an 710062 , P.R. China.

The discovery of a general strategy for organizing functional proteins into stable nanostructures with the desired dimension, shape, and function is an important focus in developing protein-based self-assembled materials, but the scalable synthesis of such materials and transfer to other substrates remain great challenges. We herein tackle this issue by creating a two-dimensional metal-protein hybrid nanofilm that is flexible and cost-effective with reliable self-recovery, stability, and multifunctionality. As it differs from traditional metal ions, we discover the capability of Sn to initiate fast amyloid-like protein assembly (occurring in seconds) by effectively reducing the disulfide bonds of native globular proteins. The Sn-initiated lysozyme aggregation at the air/water interface leads to droplet flattening, a result never before reported in a protein system, which finally affords a multifunctional 2D Sn-doped hybrid lysozyme nanofilm with an ultralarge area (., 0.2 m) within a few minutes. The hybrid film is distinctive in its ease of coating on versatile material surfaces with endurable chemical and mechanical stability, optical transparency, and diverse end uses in antimicrobial and photo-/electrocatalytic scaffolds. Our approach provides not only insights into the effect of tin ions on macroscopic self-assembly of proteins but also a controllable and scalable synthesis of a potential biomimic framework for biomedical and biocatalytic applications.
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http://dx.doi.org/10.1021/acsnano.9b01392DOI Listing
July 2019

An Atypical PML-RARA Rearrangement Resulting from Submicroscopic Insertion of the RARA Gene at the PML Locus with Novel Breakpoints within PML Exon 7b and RARA Exon 3.

Acta Haematol 2019 14;142(2):98-104. Epub 2019 May 14.

Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, China,

The diagnostic hallmark of acute promyelocytic leukemia (APL) is the reciprocal translocation t(15;17), resulting in the characteristic PML-RARA fusion; however, patients occasionally have masked PML-RARArearrangements. We report an APL case with no evidence of t(15;17) or PML-RARA rearrangement by karyotype or commercial reverse transcription polymerase chain reaction analyses. Fluorescence in situ hybridization detected a small RARA insertion signal within PML. mRNA sequencing identified a novel PML-RARA transcript generated from the juxtaposition of PMLIIa (exons 1-4, 6, and 7ab) and RARA exons (3-9), with novel breakpoints in PML exon 7b and RARA exon 3. The patient achieved molecular remission after the second consolidation chemotherapy and remains in complete remission 22 months after initial presentation. This is the first report of an APL case presenting with submicroscopic ins(15;17) and simultaneous novel breakpoints in both PML and RARA. This case highlights the importance of sequence analysis to confirm APL diagnosis and for subsequent monitoring of minimal residual disease.
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http://dx.doi.org/10.1159/000498842DOI Listing
February 2020

High-Rate, Tunable Syngas Production with Artificial Photosynthetic Cells.

Angew Chem Int Ed Engl 2019 06 30;58(23):7718-7722. Epub 2019 Apr 30.

State Key Laboratory of Photocatalysis on Energy and Environment College of Chemistry, Fuzhou University, Fuzhou, 350116, P. R. China.

An artificial photosynthetic (APS) system consisting of a photoanodic semiconductor that harvests solar photons to split H O, a Ni-SNG cathodic catalyst for the dark reaction of CO reduction in a CO -saturated NaHCO solution, and a proton-conducting membrane enabled syngas production from CO and H O with solar-to-syngas energy-conversion efficiency of up to 13.6 %. The syngas CO/H ratio was tunable between 1:2 and 5:1. Integration of the APS system with photovoltaic cells led to an impressive overall quantum efficiency of 6.29 % for syngas production. The largest turnover frequency of 529.5 h was recorded with a photoanodic N-TiO nanorod array for highly stable CO production. The CO-evolution rate reached a maximum of 154.9 mmol g  h in the dark compartment of the APS cell. Scanning electrochemical-atomic force microscopy showed the localization of electrons on the single-nickel-atom sites of the Ni-SNG catalyst, thus confirming that the multielectron reduction of CO to CO was kinetically favored.
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http://dx.doi.org/10.1002/anie.201902361DOI Listing
June 2019

The histone chaperone HIRA promotes the induction of host innate immune defences in response to HSV-1 infection.

PLoS Pathog 2019 03 22;15(3):e1007667. Epub 2019 Mar 22.

MRC-University of Glasgow Centre for Virus Research (CVR), Garscube Campus, Glasgow, Scotland, United Kingdom.

Host innate immune defences play a critical role in restricting the intracellular propagation and pathogenesis of invading viral pathogens. Here we show that the histone H3.3 chaperone HIRA (histone cell cycle regulator) associates with promyelocytic leukaemia nuclear bodies (PML-NBs) to stimulate the induction of innate immune defences against herpes simplex virus 1 (HSV-1) infection. Following the activation of innate immune signalling, HIRA localized at PML-NBs in a Janus-Associated Kinase (JAK), Cyclin Dependent Kinase (CDK), and Sp100-dependent manner. RNA-seq analysis revealed that HIRA promoted the transcriptional upregulation of a broad repertoire of host genes that regulate innate immunity to HSV-1 infection, including those involved in MHC-I antigen presentation, cytokine signalling, and interferon stimulated gene (ISG) expression. ChIP-seq analysis revealed that PML, the principle scaffolding protein of PML-NBs, was required for the enrichment of HIRA onto ISGs, identifying a role for PML in the HIRA-dependent regulation of innate immunity to virus infection. Our data identifies independent roles for HIRA in the intrinsic silencing of viral gene expression and the induction of innate immune defences to restrict the initiation and propagation of HSV-1 infection, respectively. These intracellular host defences are antagonized by the HSV-1 ubiquitin ligase ICP0, which disrupts the stable recruitment of HIRA to infecting viral genomes and PML-NBs at spatiotemporally distinct phases of infection. Our study highlights the importance of histone chaperones to regulate multiple phases of intracellular immunity to virus infection, findings that are likely to be highly pertinent in the cellular restriction of many clinically important viral pathogens.
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http://dx.doi.org/10.1371/journal.ppat.1007667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472835PMC
March 2019

Bi-clustering of metabolic data using matrix factorization tools.

Methods 2018 12 10;151:12-20. Epub 2018 Feb 10.

Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, UK. Electronic address:

Metabolic phenotyping technologies based on Nuclear Magnetic Spectroscopy (NMR) and Mass Spectrometry (MS) generate vast amounts of unrefined data from biological samples. Clustering strategies are frequently employed to provide insight into patterns of relationships between samples and metabolites. Here, we propose the use of a non-negative matrix factorization driven bi-clustering strategy for metabolic phenotyping data in order to discover subsets of interrelated metabolites that exhibit similar behaviour across subsets of samples. The proposed strategy incorporates bi-cross validation and statistical segmentation techniques to automatically determine the number and structure of bi-clusters. This alternative approach is in contrast to the widely used conventional clustering approaches that incorporate all molecular peaks for clustering in metabolic studies and require a priori specification of the number of clusters. We perform the comparative analysis of the proposed strategy with other bi-clustering approaches, which were developed in the context of genomics and transcriptomics research. We demonstrate the superior performance of the proposed bi-clustering strategy on both simulated (NMR) and real (MS) bacterial metabolic data.
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http://dx.doi.org/10.1016/j.ymeth.2018.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297113PMC
December 2018

Hydrogen peroxide acts downstream of melatonin to induce lateral root formation.

Ann Bot 2018 05;121(6):1127-1136

College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing, P.R. China.

Background And Aims: Although several studies have confirmed the beneficial roles of exogenous melatonin in lateral root (LR) formation, the molecular mechanism is still elusive. Here, the role of hydrogen peroxide (H2O2) in the induction of LR formation triggered by melatonin was investigated.

Methods: Alfalfa (Medicago sativa 'Biaogan') and transgenic Arabidopsis seedlings were treated with or without melatonin, diphenyleneiodonium (DPI, NADPH oxidase inhibitor), N,N'-dimethylthiourea (DMTU, H2O2 scavenger), alone or combined. Then, H2O2 content was determined with 2',7'-dichlorofluorescein diacetate (H2DCFDA)-dependent fluorescence and spectrophotography. Transcript levels of cell cycle regulatory genes were analysed by real-time reverse transcription-PCR.

Key Results: Application of exogenous melatonin not only increased endogenous H2O2 content but also induced LR formation in alfalfa seedlings. Consistently, melatonin-induced LR primordia exhibited an accelerated response. These inducible responses were significantly blocked when DPI or DMTU was applied. Compared with the wild-type, transgenic Arabidopsis plants overexpressing alfalfa MsSNAT (a melatonin synthesis gene) increased H2O2 accumulation and thereafter LR formation, both of which were blocked by DPI or DMTU. Similarly, melatonin-modulated expression of marker genes responsible for LR formation, including MsCDKB1;1, MsCDKB2;1, AtCDKB1;1 and AtCDKB2;1, was obviously impaired by the removal of H2O2 in both alfalfa and transgenic Arabidopsis plants.

Conclusions: Pharmacological and genetic evidence revealed that endogenous melatonin-triggered LR formation was H2O2-dependent.
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http://dx.doi.org/10.1093/aob/mcx207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946926PMC
May 2018

Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression.

Aging (Albany NY) 2017 12;9(12):2666-2694

Cancer Sciences, University of Southampton, Somers Building, Southampton General Hospital, Southampton SO16 6YD, UK.

Colorectal cancer is a global disease with increasing incidence. Mortality is largely attributed to metastatic spread and therefore, a mechanistic dissection of the signals which influence tumor progression is needed. Cancer stroma plays a critical role in tumor proliferation, invasion and chemoresistance. Here, we sought to identify and characterize exosomal microRNAs as mediators of stromal-tumor signaling. , we demonstrated that fibroblast exosomes are transferred to colorectal cancer cells, with a resultant increase in cellular microRNA levels, impacting proliferation and chemoresistance. To probe this further, exosomal microRNAs were profiled from paired patient-derived normal and cancer-associated fibroblasts, from an ongoing prospective biomarker study. An exosomal cancer-associated fibroblast signature consisting of microRNAs 329, 181a, 199b, 382, 215 and 21 was identified. Of these, miR-21 had highest abundance and was enriched in exosomes. Orthotopic xenografts established with miR-21-overexpressing fibroblasts and CRC cells led to increased liver metastases compared to those established with control fibroblasts. Our data provide a novel stromal exosome signature in colorectal cancer, which has potential for biomarker validation. Furthermore, we confirmed the importance of stromal miR-21 in colorectal cancer progression using an orthotopic model, and propose that exosomes are a vehicle for miR-21 transfer between stromal fibroblasts and cancer cells.
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http://dx.doi.org/10.18632/aging.101355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764398PMC
December 2017

Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses.

PLoS Biol 2017 12 18;15(12):e2004086. Epub 2017 Dec 18.

MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.

The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. Studies of the type I 'interferome' have mainly been carried out at a single species level, often lacking the power necessary to understand key evolutionary features of this pathway. Here, using a single experimental platform, we determined the properties of the interferomes of multiple vertebrate species and developed a webserver to mine the dataset. This approach revealed a conserved 'core' of 62 ISGs, including genes not previously associated with IFN, underscoring the ancestral functions associated with this antiviral host response. We show that gene expansion contributes to the evolution of the IFN system and that interferomes are shaped by lineage-specific pressures. Consequently, each mammal possesses a unique repertoire of ISGs, including genes common to all mammals and others unique to their specific species or phylogenetic lineages. An analysis of genes commonly down-regulated by IFN suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Our study provides a resource for the scientific community highlighting key paradigms of the type I IFN response.
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http://dx.doi.org/10.1371/journal.pbio.2004086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747502PMC
December 2017

Methane alleviates alfalfa cadmium toxicity via decreasing cadmium accumulation and reestablishing glutathione homeostasis.

Ecotoxicol Environ Saf 2018 Jan 10;147:861-871. Epub 2017 Oct 10.

College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

Although methane (CH) generation triggered by some environmental stimuli, displays the protective response against oxidative stress in plants, whether and how CH regulates plant tolerance against cadmium stress is largely unknown. Here, we discovered that cadmium (Cd) stimulated the production of CH in alfalfa root tissues. The pretreatment with exogenous CH could alleviate seedling growth inhibition. Less amounts of Cd accumulation was also observed. Consistently, in comparison with Cd stress alone, miR159 transcript was down-regulated by CH, and expression levels of its target gene ABC transporter was increased. By contrast, miR167 transcript was up-regulated, showing a relatively negative correlation with its target gene Nramp6. Meanwhile, Cd-triggered redox imbalance was improved by CH, evidenced by the reduced lipid peroxidation and hydrogen peroxide accumulation, as well as the induction of representative antioxidant genes. Further results showed that Cd-triggered decrease of the ratio of reduced/oxidized (homo)glutathione was rescued by CH. Additionally, CH-triggered alleviation of seedling growth was sensitive to a selective inhibitor of glutathione biosynthesis. Overall, above results revealed that CH-alleviated Cd accumulation at least partially, required the modulation of heavy metal transporters via miR159 and miR167. Finally, the role of glutathione homeostasis elicited by CH was preliminarily suggested.
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http://dx.doi.org/10.1016/j.ecoenv.2017.09.054DOI Listing
January 2018

Hydrogen Peroxide Is Involved in -Cyclodextrin-hemin Complex-Induced Lateral Root Formation in Tomato Seedlings.

Front Plant Sci 2017 18;8:1445. Epub 2017 Aug 18.

College of Sciences, Nanjing Agricultural UniversityNanjing, China.

Although previous results showed that -cyclodextrin-hemin complex (-CDH) could induce tomato lateral root (LR) formation, the corresponding downstream messengers are still not fully understood. In this report, similar to the inducing effects of exogenously applied hydrogen peroxide (HO), we discovered that -CDH elicited transcript upregulation, endogenous HO accumulation, and thereafter tomato LR development. Above responses were sensitive to dimethylthiourea (DMTU) and ascorbic acid (AsA), two membrane-permeable scavengers of HO, showing that accumulation of HO and LR formation were significantly blocked. The test with diphenyleneiodonium (DPI; the inhibitor of NADPH oxidase) revealed that HO mainly produced by NADPH oxidase, might be involved in LR formation triggered by -CDH. qPCR combined with pharmacological and anatomical analyses showed that -CDH-modulated several marker genes responsible for LR formation, such as , and (four cell cycle regulatory genes), and (two auxin signaling genes), (an auxin influx carrier), (encoding a member of the Aux/IAA protein family), and (two auxin efflux carriers), , and genes (two reactive oxygen species-associated genes and one LR formation-related gene), were causally related to above HO signaling. Particularly, representative proteins related to HO metabolism and lateral rooting, were specifically induced in -CDH-treated tomato seedlings. Overall, the results clearly suggested a vital role of HO in the -CDH-induced tomato LR formation, and -CDH-elicited HO-related target proteins responsible for LR formation might be, at least partially, regulated at transcriptional and translational levels.
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http://dx.doi.org/10.3389/fpls.2017.01445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563380PMC
August 2017

Methane enhances aluminum resistance in alfalfa seedlings by reducing aluminum accumulation and reestablishing redox homeostasis.

Biometals 2017 Oct 15;30(5):719-732. Epub 2017 Aug 15.

College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing, 210095, China.

Methane (CH) is emerging as a candidate of signal molecule recently. However, whether or how CH enhances plant adaptation to aluminum (Al)-contaminated environment is still unknown. In this report, the physiological roles and possible molecular mechanisms of CH in the modulation of Al toxicity in alfalfa seedlings were characterized. Our results showed that, CH pretreatment could alleviate Al-induced seedling growth inhibition and redox imbalance. The defensive effects of CH against Al toxicity including the remission of Al-induced root elongation inhibition, nutrient disorder, and relative electrolyte leakage. Moreover, contents of organic acids, including citrate, malate, and oxalate, were increased by CH. These results were paralleled by the findings of CH regulated organic acids metabolism and transport genes, citrate synthase, malate dehydrogenase, aluminum-activated malate transporter, and aluminum activated citrate transporter. Consistently, Al accumulation in seedling roots was decreased after CH treatment. In addition, Al-induced oxidative stress was also alleviated by CH, through the regulation of the activities of anti-oxidative enzymes, such as ascorbate peroxidase, superoxide dismutase, and peroxidase, as well as their corresponding transcripts. Our data clearly suggested that CH alleviates Al toxicity by reducing Al accumulation in organic acid-dependent fashion, and reestablishing redox homeostasis.
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http://dx.doi.org/10.1007/s10534-017-0040-zDOI Listing
October 2017