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1.
Insect Biochem Mol Biol ; 170: 104138, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38762126

ABSTRACT

The dysregulation of intensity and duration in innate immunity can result in detrimental effects on the body, emphasizing the crucial need for precise regulation. However, the intricate and accurate nature of innate immunity implies the existence of numerous undiscovered innate immunomodulators, particularly transcription factors. In this study, we have identified a Drosophila C2H2 zinc finger protein CG18262, named Immune-mediated Zinc Finger protein (IMZF), capable of suppressing immune responses of Imd pathway. Mechanistically, IMZF serves as a transcription factor that represses the expression of Imd and Tak1. Intriguingly, our findings also reveal that Relish, an NF-κB transcription factor, positively regulates the expression of IMZF, consequently inhibiting the activation of Imd and Tak1 to prevent an exaggerated immune response. Additionally, we have elucidated the pivotal role played by the Relish-IMZF-Imd/Tak1 axis in restoring immune homeostasis of Drosophila Imd pathway. In summary, our findings not only unveil a novel C2H2 zinc finger immunoregulatory transcription factor, IMZF, along with its specific mechanism of immune regulation, but also shed light on the dual functionality of Relish in different stages of the immune response by modulating distinct effectors. This discovery provides new insights and enlightenment into the complex regulation of Drosophila innate immunity.


Subject(s)
Drosophila Proteins , Homeostasis , Immunity, Innate , MAP Kinase Kinase Kinases , Transcription Factors , Animals , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Kinase Kinases/genetics , Drosophila melanogaster/immunology , Drosophila melanogaster/metabolism , Drosophila melanogaster/genetics , Drosophila/metabolism , Drosophila/genetics , Drosophila/immunology , Zinc Fingers
2.
Nucleic Acids Res ; 52(12): 6906-6927, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38742642

ABSTRACT

MicroRNAs (miRNAs) play crucial regulatory roles in controlling immune responses, but their dynamic expression mechanisms are poorly understood. Here, we firstly confirm that the conserved miRNA miR-210 negatively regulates innate immune responses of Drosophila and human via targeting Toll and TLR6, respectively. Secondly, our findings demonstrate that the expression of miR-210 is dynamically regulated by NF-κB factor Dorsal in immune response of Drosophila Toll pathway. Thirdly, we find that Dorsal-mediated transcriptional inhibition of miR-210 is dependent on the transcriptional repressor Su(Hw). Mechanistically, Dorsal interacts with Su(Hw) to modulate cooperatively the dynamic expression of miR-210 in a time- and dose-dependent manner, thereby controlling the strength of Drosophila Toll immune response and maintaining immune homeostasis. Fourthly, we reveal a similar mechanism in human cells, where NF-κB/RelA cooperates with E4F1 to regulate the dynamic expression of hsa-miR-210 in the TLR immune response. Overall, our study reveals a conservative regulatory mechanism that maintains animal innate immune homeostasis and provides new insights into the dynamic regulation of miRNA expression in immune response.


Subject(s)
Drosophila Proteins , Immunity, Innate , MicroRNAs , Transcription Factors , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Humans , Immunity, Innate/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Gene Expression Regulation , Drosophila melanogaster/genetics , Drosophila melanogaster/immunology , NF-kappa B/metabolism , Toll-Like Receptor 6/genetics , Toll-Like Receptor 6/metabolism , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics , Repressor Proteins/metabolism , Repressor Proteins/genetics , Signal Transduction , Cell Line , Drosophila/genetics , Drosophila/immunology , Toll-Like Receptors/genetics , Toll-Like Receptors/metabolism , Nuclear Proteins , Phosphoproteins
3.
Dev Comp Immunol ; 151: 105105, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38013113

ABSTRACT

Non-coding RNAs play important roles in the innate immunity of Drosophila, with various lncRNAs and miRNAs identified to maintain Drosophila innate immune homeostasis by regulating protein functions. However, it remains unclear whether interactions between lncRNAs and miRNAs give rise to a ceRNA network. In our previous study, we observed the highest differential expression levels of lncRNA-CR11538, lncRNA-CR33942, and lncRNA-CR46018 in wild-type flies after Gram-positive bacterial infection, prompting us to investigate their role in the regulation of Drosophila Toll immune response through RNA-seq analysis. Herein, our comprehensive bioinformatics analysis revealed that lncRNA-CR11538, lncRNA-CR33942, and lncRNA-CR46018 are involved in defense mechanisms and stimulus response. Moreover, lncRNA-CR11538 and lncRNA-CR46018 can also participate in the metabolic recovery processes following Gram-positive bacterial infection. Subsequently, we employed GSEA screening and RT-qPCR to identify seven miRNAs (miR-957, miR-1015, miR-982, miR-993, miR-1007, miR-193, and miR-978) that may be regulated by these three lncRNAs. Furthermore, we predicted the potential target genes in the Toll signaling pathway for these miRNAs and their interaction with the three lncRNAs using TargetScan and miRanda software and preliminary verification. As a result, we established a potential ceRNA regulatory network for Toll immune responses in Drosophila, comprising three lncRNAs and seven miRNAs. This study provides evidence of a ceRNA regulatory network in Drosophila Toll immune responses and offers novel insights into understanding the regulatory networks involved in the innate immunity of other animals.


Subject(s)
Gram-Positive Bacterial Infections , MicroRNAs , RNA, Long Noncoding , Animals , Drosophila/genetics , Gene Regulatory Networks , Immunity, Innate/genetics , MicroRNAs/genetics , RNA, Competitive Endogenous , RNA, Long Noncoding/genetics
4.
ChemSusChem ; 15(13): e202200186, 2022 Jul 07.
Article in English | MEDLINE | ID: mdl-35257487

ABSTRACT

2,5-Bis(hydroxymethyl)furan (BHMF) as well as furfuryl alcohol (FFA) are considered as highly valuable biomass-derived alcohols resembling aromatic monomers in polymer synthesis. Herein, a series of cobaltic nitrogen-doped carbon (Co-NC) catalysts calcinated at different temperatures were synthesized and tested for the solvent-free hydrogenation of 5-hydroxymethylfurfural (HMF) to prepare BHMF. It was found that the Co-NC catalyst calcinated at 600 °C (Co-NC-600) exhibited a superior catalytic activity in the hydrogenation reaction mainly due to the doping of graphitic N, which probably facilitated the polarization of H2 to afford H+ and H- . Consequently, Co-NC-600 offered a high BHMF/FFA yield greater than 90 % with a nearly complete conversion of HMF/furfural (FF) at the optimal conditions (80 °C, 4 h, and 5 MPa H2 ). After the hydrogenation reaction, Co-NC catalyst was facilely recycled by magnetic separation, and the obtained BHMF/FFA was then successfully transformed into hypercrosslinked polymers with an excellent CO2 /H2 storage capacity comparable to aromatic hydroxymethyl polymers. Therefore, this is a novel and facile two-step pathway for the conversion of biomass-derived HMF/FF towards functional polymers from both industrial and environmental perspectives.


Subject(s)
Alcohols , Furaldehyde , Carbon , Furaldehyde/analogs & derivatives , Hydrogenation , Polymers , Solvents
5.
J Comput Chem ; 38(24): 2100-2107, 2017 09 15.
Article in English | MEDLINE | ID: mdl-28627078

ABSTRACT

A novel type of porous organic frameworks, based on Mg-porphyrin, with diamond-like topology, named POF-Mgs is computationally designed, and the gas uptakes of CO2 , H2 , N2 , and H2 O in POF-Mgs are investigated by Grand canonical Monte Carlo simulations based on first-principles derived force fields (FF). The FF, which describes the interactions between POF-Mgs and gases, are fitted by dispersion corrected double-hybrid density functional theory, B2PLYP-D3. The good agreement between the obtained FF and the first-principle energies data confirms the reliability of the FF. Furthermore our simulation shows the presence of a small amount of H2 O (≤ 0.01 kPa) does not much affect the adsorption quantity of CO2 , but the presence of higher partial pressure of H2 O (≥ 0.1 kPa) results in the CO2 adsorption decrease significantly. The good performance of POF-Mgs in the simulation inspires us to design novel porous materials experimentally for gas adsorption and purification. © 2017 Wiley Periodicals, Inc.

6.
J Mol Model ; 20(7): 2346, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24980986

ABSTRACT

The selectivity of indoor pollution gases (including formaldehyde, benzene, and toluene) over N2 on a set of 37 covalent organic frameworks (COFs) was modeled by combining classical grand canonical Monte Carlo (GCMC) methods and periodic density functional theory with dispersion correction (DFT-D2). The pore volume, pore size, and the isosteric heat (Q st) of gases on COFs were investigated to explore the origin of the high selectivity of pollution gases over N2. We found that the size match between the pore of the COFs and the corresponding pollution gases is the key factor for high selectivity. Additionally, the Q st for the investigated four gases follows the order of toluene > benzene > formaldehyde > N2, which is consistent with the order of selectivity. Furthermore, the favorite sites and interaction energies of pollution gases on COFs were calculated by the periodic DFT-D2 method. Our simulation procedure offers an alternative approach with which to evaluate or design the best candidate porous materials in capture pollution gases.


Subject(s)
Air Pollutants/chemistry , Air Pollution, Indoor , Construction Materials , Models, Chemical , Nitrogen/chemistry , Volatile Organic Compounds/chemistry , Adsorption , Benzene/chemistry , Computer Simulation , Formaldehyde/chemistry , Gases , Models, Molecular , Monte Carlo Method , Porosity , Temperature , Toluene/chemistry
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