Publications by authors named "Zhonghua Ma"

132 Publications

Resveratrol protects intestinal integrity, alleviates intestinal inflammation and oxidative stress by modulating AhR/Nrf2 pathways in weaned piglets challenged with diquat.

Int Immunopharmacol 2021 Jul 22;99:107989. Epub 2021 Jul 22.

Laboratory of Tropical Animal Breeding, Reproduction, and Nutrition, College of Animal Science and Technology, Hainan University, Haikou 570228, PR China.

This study investigated the effects of resveratrol (RES) on intestinal morphology, antioxidant capacity, intestinal inflammation, and barrier function in weaned piglets challenged with diquat (DIQ). Thirty weaned piglets were randomly assigned to 5 treatments: non-challenged group (CON), DIQ-challenged group (DIQ), and DIQ-challenged group with 10, 30, or 90 mg/kg of RES, respectively. The trail lasted 21 days, and piglets were intraperitoneally injected with DIQ or the same amount of saline on day 15. The results showed that supplementation with 90 mg/kg RES increased (P < 0.05) jejunal villus height and villus height: crypt depth ratio, and decreased (P < 0.05) crypt depth, plasma D-lactate and diamine oxidase (DAO) compared with the DIQ group. Piglets fed with 30 or 90 mg/kg RES prevented the diquat-induced decrease (P < 0.05) of mRNA expression of occludin, claudin-1, ZO-1, and IL-10, and increase (P < 0.05) of TNF-α mRNA expression. Moreover, addition of 90 mg/kg RES increased (P < 0.05) the activities of SOD, GSH-Px, and CAT and decreased (P < 0.05) the MDA levels in jejunal mucosa compared with the DIQ group. Finally, addition of 90 mg/kg RES enhanced (P < 0.05) the mRNA expression of SOD1, SOD2, CAT, GPx1, and HO-1, and increased (P < 0.05) mRNA and protein expression of Nrf2, NQO1, aryl hydrocarbon receptor (AhR), and cytochrome P450 family 1 member A1 (CYP1A1). These data indicated that supplementation with 90 mg/kg RES was effective in protecting the intestinal integrity, alleviating intestinal inflammation and oxidative stress by activating AhR/Nrf2 pathways in diquat-challenged piglets.
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http://dx.doi.org/10.1016/j.intimp.2021.107989DOI Listing
July 2021

In Situ Electrochemical Mn(III)/Mn(IV) Generation of Mn(II)O Electrocatalysts for High-Performance Oxygen Reduction.

Nanomicro Lett 2020 Aug 11;12(1):161. Epub 2020 Aug 11.

State Key Lab of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-020-00500-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770805PMC
August 2020

Post-translational regulation of autophagy is involved in intra-microbiome suppression of fungal pathogens.

Microbiome 2021 06 6;9(1):131. Epub 2021 Jun 6.

State Key Laboratory of Rice Biology, and Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.

Background: Microbiome interactions are important determinants for ecosystem functioning, stability, and health. In previous studies, it was often observed that bacteria suppress potentially pathogenic fungal species that are part of the same plant microbiota; however, the underlying microbe-microbe interplay remains mostly elusive. Here, we explored antagonistic interactions of the fungus Fusarium graminearum and bacterium Streptomyces hygroscopicus at the molecular level. Both are ubiquitous members of the healthy wheat microbiota; under dysbiosis, the fungus causes devastating diseases.

Results: In co-cultures, we found that Streptomyces alters the fungal acetylome leading to substantial induction of fungal autophagy. The bacterium secrets rapamycin to inactivate the target of rapamycin (TOR), which subsequently promotes the degradation of the fungal histone acetyltransferase Gcn5 through the 26S proteasome. Gcn5 negatively regulates fungal autophagy by acetylating the autophagy-related protein Atg8 at the lysine site K13 and blocking cellular relocalization of Atg8. Thus, degradation of Gcn5 triggered by rapamycin was found to reduce Atg8 acetylation, resulting in autophagy induction in F. graminearum.

Conclusions: Autophagy homeostasis plays an essential role in fungal growth and competition, as well as for virulence. Our work reveals a novel post-translational regulation of autophagy initiated by a bacterial antibiotic. Rapamycin was shown to be a powerful modulator of bacteria-fungi interactions with potential importance in explaining microbial homeostasis in healthy plant microbiomes. The autophagic process provides novel possibilities and targets to biologically control pathogens. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01077-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182927PMC
June 2021

The RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium.

Nat Commun 2021 05 11;12(1):2661. Epub 2021 May 11.

State Key Laboratory of Rice Biology, the Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Precursor messenger RNA (pre-mRNA) splicing is an essential and tightly regulated process in eukaryotic cells; however, the regulatory mechanisms for the splicing are not well understood. Here, we characterize a RNA binding protein named FgRbp1 in Fusarium graminearum, a fungal pathogen of cereal crops worldwide. Deletion of FgRbp1 leads to reduced splicing efficiency in 47% of the F. graminearum intron-containing gene transcripts that are involved in various cellular processes including vegetative growth, development, and virulence. The human ortholog RBM42 is able to fully rescue the growth defects of ΔFgRbp1. FgRbp1 binds to the motif CAAGR in its target mRNAs, and interacts with the splicing factor FgU2AF23, a highly conserved protein involved in 3' splice site recognition, leading to enhanced recruitment of FgU2AF23 to the target mRNAs. This study demonstrates that FgRbp1 is a splicing regulator and regulates the pre-mRNA splicing in a sequence-dependent manner in F. graminearum.
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http://dx.doi.org/10.1038/s41467-021-22917-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113354PMC
May 2021

Interplay of two transcription factors for recruitment of the chromatin remodeling complex modulates fungal nitrosative stress response.

Nat Commun 2021 05 6;12(1):2576. Epub 2021 May 6.

State Key Laboratory of Rice Biology, Zhejiang University, Hangzhou, China.

Nitric oxide (NO) is a diffusible signaling molecule that modulates animal and plant immune responses. In addition, reactive nitrogen species derived from NO can display antimicrobial activities by reacting with microbial cellular components, leading to nitrosative stress (NS) in pathogens. Here, we identify FgAreB as a regulator of the NS response in Fusarium graminearum, a fungal pathogen of cereal crops. FgAreB serves as a pioneer transcription factor for recruitment of the chromatin-remodeling complex SWI/SNF at the promoters of genes involved in the NS response, thus promoting their transcription. FgAreB plays important roles in fungal infection and growth. Furthermore, we show that a transcription repressor (FgIxr1) competes with the SWI/SNF complex for FgAreB binding, and negatively regulates the NS response. NS, in turn, promotes the degradation of FgIxr1, thus enhancing the recruitment of the SWI/SNF complex by FgAreB.
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http://dx.doi.org/10.1038/s41467-021-22831-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102577PMC
May 2021

Discovery of Frenolicin B as Potential Agrochemical Fungicide for Controlling Head Blight on Wheat.

J Agric Food Chem 2021 Feb 15;69(7):2108-2117. Epub 2021 Feb 15.

Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Northeast Agricultural University, Harbin 150030, People's Republic of China.

In this study, the supernatant extract from fermentation broth of sp. NEAU-H3 showed strong antifungal activity against strain PH-1 and . Three known pyranonaphthoquinones were isolated by means of an activity-guided method, and frenolicin B was characterized as the main active ingredient. Frenolicin B displayed strong antifungal activity against strain PH-1 with an EC value of 0.51 mg/L, which is lower than that of carbendazim (0.78 mg/L) but higher than that of phenamacril (0.18 mg/L). Frenolicin B could also strongly inhibit the mycelial growth of species, including and , as well as carbendazim-resistant strains isolated from field, with EC values of 0.25-0.92 mg/L. Results from field experiments showed that the efficacy of frenolicin B in controlling head blight at a treatment concentration of 75 g ai/ha was better than those of phenamacril (375 g ai/ha) and carbendazim (600 g ai/ha) or had no significant difference with that of phenamacril (375 g ai/ha) in 2 years. Scanning electron microscope and transmission electron microscope observations revealed that after treating mycelia with frenolicin B, the mycelia appeared aberrant and had an uneven thickness and swelling, the cytoplasm had disintegrated, and some cell contents were lost. Transcriptome analysis suggests that frenolicin B might inhibit the metabolism of nucleotides and energy by affecting genes involved in phosphorus utilization but did not affect the expression of myosin 5, which is the specific target of phenamacril. These findings indicate that frenolicin B may be a potential agrochemical fungicide for controlling head blight.
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http://dx.doi.org/10.1021/acs.jafc.0c04277DOI Listing
February 2021

Development and Validation of a DFT-Based Force Field for a Hydrated Homoalanine Polypeptide.

J Phys Chem B 2021 02 8;125(6):1568-1581. Epub 2021 Feb 8.

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, United States.

A new force field has been created for simulating hydrated alanine polypeptides using the adaptive force matching (AFM) method. Only density functional theory calculations using the Perdew-Burke-Ernzerhof exchange-correlation functional and the D3 dispersion correction were used to fit the force field. The new force field, AFM2020, predicts NMR scalar coupling constants for hydrated homopolymeric alanine in better agreements with experimental data than several other models including those fitted directly to such data. For Ala, the new force field shows about 15% helical conformations, 20% conformation in the β basin, and 65% polyproline II. The predicted helical population of short hydrated alanine is higher than previous estimates based on the same experimental data. Gas-phase simulations indicate that the force field developed by AFM solution-phase data is likely to produce a reasonable conformation distribution when hydration water is no longer present, such as the interior of a protein.
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http://dx.doi.org/10.1021/acs.jpcb.0c11618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899179PMC
February 2021

Advances in Understanding Fungicide Resistance in in China.

Phytopathology 2021 Mar 4;111(3):455-463. Epub 2021 Feb 4.

Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Gray mold, caused by , is a devastating disease that causes significant yield losses in various economically important plants. Fungicide application is one of the main strategies for management of gray mold; however, has developed resistance to various groups of fungicide. In China, benzimidazole-, dicarboximide-, and quinone outside inhibitor-resistant populations of have become dominant. Substitute mutations in fungicide target genes are responsible for resistance in . Based on known resistance mechanisms, molecular methods including loop-mediated isothermal amplification have been developed for rapid detection of resistant isolates of Because is able to quickly develop resistance to various fungicides, various integrated strategies have been implemented in the last decade, including biological and agricultural practices, to manage fungicide resistance in .
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http://dx.doi.org/10.1094/PHYTO-07-20-0313-IADOI Listing
March 2021

EGR1-mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer.

Cell Prolif 2021 Jan 3;54(1):e12922. Epub 2020 Nov 3.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China.

Objectives: Long non-coding RNAs (lncRNAs) are key mediators in various malignancies. Linc01503 was previously elucidated to promote gastric cancer (GC) cell invasion. However, the upstream mechanism of linc01503 and its involvement in GC cell cycle, apoptosis and tumorigenesis still remain unclear.

Materials And Methods: Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays were implicated to detect linc01503 level in GC. The role of linc01503 was detected by in vitro functional assays and in vivo xenograft tumour models. The association between linc01503 and its upstream effector was identified by chromatin immunoprecipitation (ChIP) assays. The mechanistic model of linc01503 was clarified using subcellular separation, fluorescence in situ hybridization, RNA-sequencing, RNA immunoprecipitation (RIP) and ChIP assays.

Results: Linc01503 was remarkably elevated in GC and tightly linked with the overall survival of patients with GC. The key transcription factor early growth response protein 1 (EGR1) critically activated the transcription of linc01503. Functionally, linc01503 knockdown resulted in the activation of apoptosis and G1/G0 phase arrest in GC. Mechanistically, linc01503 interacted with histone modification enzyme enhancer of zeste 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1), thereby mediating the transcriptional silencing of dual-specificity phosphatase 5 (DUSP5) and cyclin-dependent kinase inhibitor 1A (CDKN1A) in GC.

Conclusions: EGR1-activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics.
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http://dx.doi.org/10.1111/cpr.12922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791171PMC
January 2021

The m6A epitranscriptome opens a new charter in immune system logic.

Epigenetics 2021 Aug 19;16(8):819-837. Epub 2020 Oct 19.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing, China.

N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate network architecture by which m6A epitranscriptome impacts on immune response and function. However, it was only until recently that the mechanisms underlying the involvement of m6A modification in immune system were uncovered. Here, we systematically review the m6A involvement in the regulation of innate and adaptive immune cells. Further, the interplay between m6A modification and anti-inflammatory, anti-viral and anti-tumour immunity is also comprehensively summarized. Finally, we focus on the future prospects of m6A modification in immune modulation. A better understanding of the crosstalk between m6A modification and immune system is of great significance to reveal new pathogenic pathways and to develop promising therapeutic targets of diseases.
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http://dx.doi.org/10.1080/15592294.2020.1827722DOI Listing
August 2021

N6-methyladenosine (m6A) RNA modification in cancer stem cells.

Stem Cells 2020 Sep 27. Epub 2020 Sep 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing People's Republic of, China.

Cancer stem cells (CSCs), a unique subset of undifferentiated cells with stem cell-like properties, have emerged as driving forces in mediating tumor growth, metastasis, and therapeutic resistance. Recent advances have highlighted that N6-methyladenosine (m6A) RNA modification plays an important role in cancer biology and CSCs. Dynamic m6A decoration has been demonstrated to be involved in CSC generation and maintenance, governing cancer progression and therapeutic resistance. In this review, we provide the first overview of the current knowledge of m6A modification implicated in CSCs and their impact on CSC properties, tumor progression, and responses to treatment. Finally, we also highlight the potential of m6A machinery as novel targets for cancer therapeutics. The involvement of m6A modification in CSCs provides a new direction for exploring cancer pathogenesis and inspires the development of effective strategies to fully eliminate both cancer cells and CSCs.
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http://dx.doi.org/10.1002/stem.3279DOI Listing
September 2020

Effects of Mutations in the Phenamacril-Binding Site of Myosin-1 on Its Motor Function and Phenamacril Sensitivity.

ACS Omega 2020 Sep 20;5(34):21815-21823. Epub 2020 Aug 20.

Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Phenamacril is a -specific fungicide used for head blight management. The target of phenamacril is FgMyo1, the sole class I myosin in . The point mutation S217L in FgMyo1 is responsible for the high resistance of to phenamacril. Recent structural studies have shown that phenamacril binds to the 50 kDa cleft of the FgMyo1 motor domain, forming extensive interactions, including a hydrogen bond between the cyano group of phenamacril and the hydroxyl group of S217. Here, we produced FgMyo1, a truncated FgMyo1 composed of the motor domain and two IQ motifs complexed with the calmodulin in insect Sf9 cells. Phenamacril potently inhibited both the basal and the actin-activated ATPase activities of FgMyo1, with an IC in a micromolar range. S217 mutations of FgMyo1 substantially increased the IC of phenamacril. S217T or S217L each increased the IC of phenamacril for ∼60-fold, while S217A only increased the IC for ∼4-fold. These results indicate that the hydroxyl group of S217 plays an important, but nonessential role in phenamacril binding and that the bulky side chain at the position 217 sterically hinders phenamacril binding. On the other hand, S217P, which might alter the local conformation of the phenamacril-binding site, completely abolished the phenamacril inhibition. Because the cyano group of phenamacril does not form discernible interactions with FgMyo1 other than the nonessential hydrogen bond with the S217 hydroxyl group, we propose the cyano group of phenamacril as a key modification site for the development of novel fungicides.
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http://dx.doi.org/10.1021/acsomega.0c02886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469408PMC
September 2020

System-wide characterization of subtilases reveals that subtilisin-like protease FgPrb1 of Fusarium graminearum regulates fungal development and virulence.

Fungal Genet Biol 2020 11 2;144:103449. Epub 2020 Sep 2.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Zhejiang University, Hangzhou 310058, China.

Subtilases represent the second largest subfamily of serine proteases, and are important for various biological processes. However, the biological function of subtilases has not been systematically characterized in plant pathogens. In present study, 32 subtilases were identified in the genome of wheat scab fungus Fusarium graminearum, a devastating cereal plant pathogen. Deletion mutants of each subtilase were obtained and functionally characterized. Among them, the deletion of FgPrb1 resulted in greatly reduced virulence of F. graminearum. The regulatory mechanisms of FgPrb1 in virulence were investigated in details. Our results showed that the loss of FgPrb1 led to defects in deoxynivalenol (DON) production, responses to environmental stimuli, and lipid metabolism. Additionally, we found that FgPrb1 was involved in autophagy regulation. Taken together, the systematic functional characterization of subtilases showed that the FgPrb1 of F. graminearum is critical for plant infection by regulating multiple different cellular processes.
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http://dx.doi.org/10.1016/j.fgb.2020.103449DOI Listing
November 2020

Idiopathic intracranial hypertension in patients with anemia: A retrospective observational study.

PLoS One 2020 31;15(7):e0236828. Epub 2020 Jul 31.

Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Idiopathic intracranial hypertension (IIH) mostly affects obese women in childbearing age, leading to frustrating headache and permanent visual impairment. The exact etiology of this condition is poorly understood, and the population at risk and clinical presentation seems to be homogeneous. However, little attention has been paid to the clinical features of IIH patients with anemia. We herein performed a retrospective observational study by using the data of patients with presumed IIH who were referred to the neurology department of Beijing Tongren Hospital from January 2014 to August 2019 to describe the clinical features and radiological findings in patients with IIH and anemia, and compared these with those without anemia. The patients were divided into two groups based on the presence of anemic diseases. Clinical data including demographic characteristics, clinical features, past medical history, laboratory and neuroradiological findings, diagnoses, treatments and prognosis of these patients were reviewed and compared in both the groups. A total of 153 patients with IIH were enrolled, which included 22 cases with anemia (mean age, 33.23±9.68 years; 19 [86.36%] female) and 131 cases without anemia (mean age 37.11±11.56 years; 97 [74.05%] female). In the anemia group, 19/22 cases had iron deficiency anemia and 3/22 had renal anemia. Compared with patients in the non-anemia group, IIH patients with anemia had a shorter disease course, and tended to present pulsatile tinnitus and transverse sinus stenosis (TSS), faster and better prognosis after treatments for correcting anemia and reducing intracranial pressure. Our findings highlighted the importance of obtaining full blood counts in IIH patients with subacute onset, and provided appropriate and prompt treatments if proven anemic in order to bring better outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236828PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394431PMC
September 2020

WITHDRAWN: Correlation Factor Analysis of Infections and Neurological Complications after Interventional Chemoembolization of Liver Cancer by Digital Subtraction Angiography Images.

Neurosci Lett 2020 Jun 23:135200. Epub 2020 Jun 23.

Cath Lab, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning, China. Electronic address:

This article has been withdrawn at the request of the Editor-in-Chief. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.neulet.2020.135200DOI Listing
June 2020

The RasGEF FgCdc25 regulates fungal development and virulence in Fusarium graminearum via cAMP and MAPK signalling pathways.

Environ Microbiol 2020 12 15;22(12):5109-5124. Epub 2020 Jul 15.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.

Ras GTPases act as molecular switches to control various cellular processes by coupling integrated signals in eukaryotes. Activities of Ras GTPases are triggered by Ras GTPase guanine nucleotide exchange factors (RasGEFs) in general, whereas the role of RasGEF in plant pathogenic fungi is largely unknown. In this study, we characterized the only RasGEF protein in Fusarium graminearum, FgCdc25, by combining genetic, cytological and phenotypic strategies. FgCdc25 directly interacted with RasGTPase FgRas2, but not FgRas1, to regulate growth and sexual reproduction. Mutation of the FgCDC25 gene resulted in decreased toxisome formation and deoxynivalenol (DON) production, which was largely depended on cAMP signalling. In addition, FgCdc25 indirectly interacted with FgSte11 in FgSte11-Ste7-Gpmk1 cascade, and the ΔFgcdc25 strain totally abolished the formation of infection structures and was nonpathogenic in planta, which was partially recovered by addition of exogenous cAMP. In contrast, FgCdc25 directly interplayed with FgBck1 in FgBck1-MKK1-Mgv1 cascade to negatively control cell wall integrity. Collectively, these results suggest that FgCdc25 modulates cAMP and MAPK signalling pathways and further regulates fungal development, DON production and plant infection in F. graminearum.
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http://dx.doi.org/10.1111/1462-2920.15129DOI Listing
December 2020

Host-induced gene silencing of multiple genes of Fusarium graminearum enhances resistance to Fusarium head blight in wheat.

Plant Biotechnol J 2020 12 11;18(12):2373-2375. Epub 2020 Jun 11.

Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

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http://dx.doi.org/10.1111/pbi.13401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680546PMC
December 2020

Correction: Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer.

Mol Omics 2020 Apr 24;16(2):174-175. Epub 2020 Feb 24.

The Second Clinical Medical College of Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.

Correction for 'Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer' by Zhonghua Ma et al., Mol. BioSyst., 2017, 13, 2350-2361.
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http://dx.doi.org/10.1039/c9mo90013fDOI Listing
April 2020

Circular RNAs in the tumour microenvironment.

Mol Cancer 2020 01 14;19(1). Epub 2020 Jan 14.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.

Background: Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs (ncRNAs) widely expressed in eukaryotic cells. Mounting evidence has highlighted circRNAs as critical regulators of various tumours. More importantly, circRNAs have been revealed to recruit and reprogram key components involved in the tumour microenvironment (TME), and mediate various signaling pathways, thus affecting tumourigenesis, angiogenesis, immune response, and metastatic progression. In this review, we briefly introduce the biogenesis, characteristics and classification of circRNAs, and describe various mechanistic models of circRNAs. Further, we provide the first systematic overview of the interplay between circRNAs and cellular/non-cellular counterparts of the TME and highlight the potential of circRNAs as prospective biomarkers or targets in cancer clinics. Finally, we discuss the biological mechanisms through which the circRNAs drive development of resistance, revealing the mystery of circRNAs in drug resistance of tumours.

Short Conclusion: Deep understanding the emerging role of circRNAs and their involvements in the TME may provide potential biomarkers and therapeutic targets for cancer patients. The combined targeting of circRNAs and co-activated components in the TME may achieve higher therapeutic efficiency and become a new mode of tumour therapy in the future.
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http://dx.doi.org/10.1186/s12943-019-1113-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958568PMC
January 2020

TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2.

Mol Cancer 2020 01 10;19(1). Epub 2020 Jan 10.

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

Background: Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms.

Methods: LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays.

Results: It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions.

Conclusions: Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.
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http://dx.doi.org/10.1186/s12943-019-1104-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953272PMC
January 2020

LncRNA SNHG15: A new budding star in human cancers.

Cell Prolif 2020 Jan 27;53(1):e12716. Epub 2019 Nov 27.

Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

Objectives: Long non-coding RNAs (lncRNAs) represent an important group of non-coding RNAs (ncRNAs) with more than 200 nucleotides in length that are transcribed from the so-called genomic "dark matter." Mounting evidence has shown that lncRNAs have manifested a paramount function in the pathophysiology of human diseases, especially in the pathogenesis and progression of cancers. Despite the exponential growth in lncRNA publications, our understanding of regulatory mechanism of lncRNAs is still limited, and a lot of controversies remain in the current lncRNA knowledge.The purpose of this article is to explore the clinical significance and molecular mechanism of SNHG15 in tumors.

Materials & Methods: We have systematically searched the Pubmed, Web of Science, Embase and Cochrane databases. We provide an overview of current evidence concerning the functional role, mechanistic models and clinical utilities of SNHG15 in human cancers in this review.

Results: Small nucleolar RNA host gene 15 (SNHG15), a novel lncRNA, is identified as a key regulator in tumorigenesis and progression of various human cancers, including colorectal cancer (CRC), gastric cancer (GC), pancreatic cancer (PC) and hepatocellular carcinoma (HCC). Dysregulation of SNHG15 has been revealed to be dramatically correlated with advanced clinicopathological factors and predicts poor prognosis, suggesting its potential clinical value as a promising biomarker and therapeutic target for cancer patients.

Conclusions: LncRNA SNHG15 may serve as a prospective and novel biomarker for molecular diagnosis and therapeutics in patients with cancer.
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http://dx.doi.org/10.1111/cpr.12716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985667PMC
January 2020

Leveraging local MP2 to reduce basis set superposition errors: An efficient first-principles based force-field for carbon dioxide.

J Chem Phys 2019 Nov;151(18):184501

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA.

Pairwise additive model potentials for CO were developed by fitting to gradients computed with the local second order Møller Plesset Perturbation theory (LMP2) method, with and without consideration of 3-body dispersion using adaptive force matching. Without fitting to experiments, all models gave good predictions of properties of CO, such as the density-temperature diagram, diffusion constants, and radial distribution functions. For the prediction of vibrational spectra, the inclusion of a bond-bond coupling term has been shown to be important. The CO models developed only have pairwise additive terms, thus allowing microsecond time scale simulations to be performed with practical computational cost. LMP2 performed significantly better than second order Møller Plesset Perturbation theory (MP2) for the development of the CO model. This is attributed to the appreciable reduction in the basis set superposition error when the localized method was used. It is argued that LMP2 is a more appropriate method than MP2 for force matching for systems where the basis set superposition error is large.
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http://dx.doi.org/10.1063/1.5124811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008884PMC
November 2019

Capping proteins regulate fungal development, DON-toxisome formation and virulence in Fusarium graminearum.

Mol Plant Pathol 2020 02 6;21(2):173-187. Epub 2019 Nov 6.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.

Deoxynivalenol (DON) is an important trichothecene mycotoxin produced by the cereal pathogen Fusarium graminearum. DON is synthesized in organized endoplasmic reticulum structures called toxisomes. However, the mechanism for toxisome formation and the components of toxisomes are not yet fully understood. In a previous study, we found that myosin I (FgMyo1)-actin cytoskeleton participated in toxisome formation. In the current study, we identified two new components of toxisomes, the actin capping proteins (CAPs) FgCapA and FgCapB. These two CAPs form a heterodimer in F. graminearum, and physically interact with FgMyo1 and Tri1. The deletion mutants ΔFgcapA and ΔFgcapB and the double deletion mutant ΔΔFgcapA/B dramatically reduced hyphal growth, asexual and sexual reproduction and endocytosis. More importantly, the deletion mutants markedly disrupted toxisome formation and DON production, and attenuated virulence in planta. Collectively, these results suggest that the actin CAPs are associated with toxisome formation and contribute to the virulence and development of F. graminearum.
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http://dx.doi.org/10.1111/mpp.12887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988429PMC
February 2020

A fungal ABC transporter FgAtm1 regulates iron homeostasis via the transcription factor cascade FgAreA-HapX.

PLoS Pathog 2019 09 23;15(9):e1007791. Epub 2019 Sep 23.

State Key Laboratory of Rice Biology, Zhejiang University, Hangzhou, China.

Iron homeostasis is important for growth, reproduction and other metabolic processes in all eukaryotes. However, the functions of ATP-binding cassette (ABC) transporters in iron homeostasis are largely unknown. Here, we found that one ABC transporter (named FgAtm1) is involved in regulating iron homeostasis, by screening sensitivity to iron stress for 60 ABC transporter mutants of Fusarium graminearum, a devastating fungal pathogen of small grain cereal crops worldwide. The lack of FgAtm1 reduces the activity of cytosolic Fe-S proteins nitrite reductase and xanthine dehydrogenase, which causes high expression of FgHapX via activating transcription factor FgAreA. FgHapX represses transcription of genes for iron-consuming proteins directly but activates genes for iron acquisition proteins by suppressing another iron regulator FgSreA. In addition, the transcriptional activity of FgHapX is regulated by the monothiol glutaredoxin FgGrx4. Furthermore, the phosphorylation of FgHapX, mediated by the Ser/Thr kinase FgYak1, is required for its functions in iron homeostasis. Taken together, this study uncovers a novel regulatory mechanism of iron homeostasis mediated by an ABC transporter in an important pathogenic fungus.
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http://dx.doi.org/10.1371/journal.ppat.1007791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788720PMC
September 2019

Geminivirus C4 antagonizes the HIR1-mediated hypersensitive response by inhibiting the HIR1 self-interaction and promoting degradation of the protein.

New Phytol 2020 02 29;225(3):1311-1326. Epub 2019 Oct 29.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, Zhejiang, 310058, China.

Tomato leaf curl Yunnan virus (TLCYnV)-encoded C4 protein induces the upregulation of the hypersensitive induced reaction 1 (HIR1) gene but interferes with the HIR1-mediated hypersensitive response (HR). HIR1 self-interaction is essential for the HIR1-induced HR. TLCYnV C4 impairs the HIR1 self-interaction and concomitantly increases the amount of Leucine-Rich Repeat protein 1 (LRR1), a modulator of HIR1, which binds to HIR1. LRR1 promotes the degradation of HIR1, compromising the HIR1-mediated HR. This study provides new insights into the mechanisms employed by a viral protein to counter host resistance through the cooption of the host regulatory system.
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http://dx.doi.org/10.1111/nph.16208DOI Listing
February 2020

Clinical analysis of severe visual loss caused by inhalational methanol poisoning in a chronic process with acute onset:a retrospective clinical analysis.

BMC Ophthalmol 2019 Jun 7;19(1):124. Epub 2019 Jun 7.

Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.

Background: To analyze the clinical features and prognosis of the visual loss resulted from inhalational methanol poisoning in 8 Chinese patients.

Methods: Eight consecutive patients seen at the Beijing Tongren Hospital of Capital Medical University, Beijing, China between January 2003 to August 2017, with complains of vision loss in both eyes, identified as inhalational methanol poisoning. Detailed medical history was extracted. All patients underwent optic nerve and brain magnetic resonance imaging (MRI) scan, laboratory tests, and visual function analysis. Treatment protocols were large dosage of methylprednisolone and B vitamins over 3 months. Patients were seen at 3-month intervals until a year.

Results: Eight patients with optic neuropathy caused by inhalation toxicity of methanol were under observation, whose methanol-contact time spans were form 4 days to 5 years for occupational exposure. All the patients had acute onset, transient systemic symptoms on early stage, both eyes involved with severe visual impairment (visual acuity 0.1 or even worse). Retrobulbar optic nerves (ONs) were the major sites involved. Optic nerve MRI scan showed increased signal of bilateral ONs in the orbit and the canal parts, with enhancement. After treatment, the visual function of these patients got improved in different degree in a year follow-up, but not satisfactorily.

Conclusions: Inhalational methanol toxicity may lead to serious damage to ON in a process of chronic intoxication with acute attack, and with poor prognosis.
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http://dx.doi.org/10.1186/s12886-019-1127-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554876PMC
June 2019

High-Density 3D Printable Chipless RFID Tag with Structure of Passive Slot Rings.

Sensors (Basel) 2019 Jun 3;19(11). Epub 2019 Jun 3.

College of IoT Engineering, Jiangnan University, Wuxi 214122, China.

A three-dimensional (3D) printable chipless radio frequency identification (RFID) tag, with high density and sensitivity, is proposed and fulfilled on insulator substrates. By printing a rectangular slot ring and designing specific geometry on the substrate, the printed structure shows high sensitivity in a resonant manner, with the benefits of high density and low cost. Considering the multiple rectangular rings with different sizes in a concentric distribution, a bit coding sequence can be observed in frequency spectra because of the corresponding different resonant frequencies aroused by the printed slots. In this way, the 3D printable chipless RFID tag can be fulfilled by adopting the structure of the rectangular slot ring on the insulated substrates. The main characteristics of the designed rectangular slot rings are verified on both flexible and solid substrates. A 12-bit chipless tag based on the slot ring structures is designed and implemented. The simulation and experiment results show good agreement on its characteristics. The frequency response reveals the fact that the 2th, 3th and 4th harmonic do not exist, which is a unique merit for improving the encoding capacity and the sensitivity of the corresponding reader. The electric field direction of the electromagnetic wave of the reader excitation tag is demonstrated to be wide, up to 90° on the tag horizontal plane, 30° on the vertical direction.
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http://dx.doi.org/10.3390/s19112535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603627PMC
June 2019

The b-ZIP transcription factor FgTfmI is required for the fungicide phenamacril tolerance and pathogenecity in Fusarium graminearum.

Pest Manag Sci 2019 Dec 3;75(12):3312-3322. Epub 2019 Jun 3.

State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Background: Fusarium head blight (FHB) is a devastating disease of cereal crops worldwide mainly caused by Fusarium graminearum. Due to the unavailability of FHB-resistant wheat cultivars, chemical fungicide application is currently the most effective approach for controlling FHB now. In the last few years, a novel cyanoacrylate fungicide, phenamacril, has been widely used in China for FHB disease management. In previous studies, we identified that myosin I (FgMyo1) is the target of phenamacril and is essential for mycotoxin deoxynivalenol (DON) biosynthesis and fungal growth. However, the regulation of FgMYO1 gene expression is still largely unknown.

Results: In this study, we identified a b-ZIP transcription factor, FgTfmI, which regulates the mRNA expression of FgMYO1 upon phenamacril treatment. The FgTfmI directly binds to the promoter region of FgMYO1, and is required for the upregulation of FgMYO1 in response to phenamacril treatment. The deletion mutant of FgTFMI (ΔFgTfmI) displayed a slight growth defect, while it showed hypersensitivity to phenamacril, but not to other tested fungicides. FgTfmI also contributed to DON biosynthesis and the infection process in planta.

Conclusions: The transcription factor FgTfmI plays an important role in regulating transcription of the genes involved in phenamacril tolerance, DON biosynthesis and virulence in F. graminearum. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5454DOI Listing
December 2019

Control of Wheat Fusarium Head Blight by Heat-Stable Antifungal Factor (HSAF) from .

Plant Dis 2019 Jun 17;103(6):1286-1292. Epub 2019 Apr 17.

1 Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Jiangsu Key Laboratory for Food Quality and Safety, State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014, P.R. China.

Heat-stable antifungal factor (HSAF), which belongs to the polycyclic tetramate macrolactam family, was isolated from fermentations and exhibited inhibitory activities against a wide range of fungal pathogens. In this study, the antifungal activity of HSAF against in vitro and in vivo was investigated. A total of 50% of mycelial growth of was suppressed with 4.1 μg/ml of HSAF (EC value). HSAF treatment resulted in abnormal morphology of the hyphae, such as curling, apical swelling, and depolarized growth. Furthermore, HSAF adequately inhibited conidial germination and conidiation of with an inhibition rate of 100% when 1 and 6 μg/ml of HSAF were applied, respectively. HSAF caused ultrastructural changes of , including cell wall thickening and plasmolysis. Moreover, the application of HSAF significantly controlled Fusarium head blight in wheat caused by in the field. Overall, these results indicate that HSAF has potential for development as a fungicide against .
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http://dx.doi.org/10.1094/PDIS-09-18-1517-REDOI Listing
June 2019

The endocytic cargo adaptor complex is required for cell-wall integrity via interacting with the sensor FgWsc2B in Fusarium graminearum.

Curr Genet 2019 Aug 5;65(4):1071-1080. Epub 2019 Apr 5.

Institute of Biotechnology, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.

AP2 is a heterotetrameric clathrin adaptor complex that owns important roles in vesicle generation and cargo recognition. Cell-wall integrity (CWI) pathway is essential for fungal development, virulence, and adaptation to environment stresses. To date, the relationship between AP2 and CWI is largely unknown in phytopathogenic fungi. In this study, we identified the adaptor complex FgAP2 in Fusarium graminearum. The biological function analysis showed that FgAP2 complex contains FgAP2α, FgAP2β, FgAP2σ, and FgAP2μ, and the subunit FgAP2μ, which is required for hyphal growth, conidiation, CWI, and virulence. Yeast two-hybrid showed that FgAP2μ interacts with the CWI sensor FgWsc2B. Consistently, western blotting analysis revealed that FgWsc2B positively regulates phosphorylation of FgMgv1, the MAP kinase of CWI. Moreover, the FgWsc2B deletion mutant exhibited defects in hyphal growth, virulence, and response to CWI damaging agents. Taken together, our data indicated that FgAP2μ is involved in CWI and virulence via interacting with FgWsc2B in F. graminearum.
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http://dx.doi.org/10.1007/s00294-019-00961-3DOI Listing
August 2019
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