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Cost-effective and high-efficiency catalysts play a central role in various sustainable electrochemical energy conversion technologies that are being developed to generate clean energy while reducing carbon emissions, such as fuel cells, metal-air batteries, water electrolyzers, and carbon dioxide conversion. In this context, a recent climax in the exploitation of advanced earth-abundant catalysts has been witnessed for diverse electrochemical reactions involved in the above mentioned sustainable pathways. In particular, polymer catalysts have garnered considerable interest and achieved substantial progress very recently, mainly owing to their pyrolysis-free synthesis, highly tunable molecular composition and microarchitecture, readily adjustable electrical conductivity, and high stability. In this review, we present a timely and comprehensive overview of the latest advances in organic polymers as emerging materials for powerful electrocatalysts. First, we present the general principles for the design of polymer catalysts in terms of catalytic activity, electrical conductivity, mass transfer, and stability. Then, the state-of-the-art engineering strategies to tailor the polymer catalysts at both molecular (i.e., heteroatom and metal atom engineering) and macromolecular (i.e., chain, topology, and composition engineering) levels are introduced. Particular attention is paid to the insightful understanding of structure-performance correlations and electrocatalytic mechanisms. The fundamentals behind these critical electrochemical reactions, including the oxygen reduction reaction, hydrogen evolution reaction, CO2 reduction reaction, oxygen evolution reaction, and hydrogen oxidation reaction, as well as breakthroughs in polymer catalysts, are outlined as well. Finally, we further discuss the current challenges and suggest new opportunities for the rational design of advanced polymer catalysts. By presenting the progress, engineering strategies, insightful understandings, challenges, and perspectives, we hope this review can provide valuable guidelines for the future development of polymer catalysts.
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Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3-mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer.
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Neoplasias Colorretais , Fator de Iniciação 3 em Eucariotos , Regulação Neoplásica da Expressão Gênica , Fosfoglicerato Desidrogenase , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/fisiopatologia , Metiltransferases/metabolismo , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , RNA Mensageiro/metabolismo , Fator de Iniciação 3 em Eucariotos/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Regulação para Cima , Técnicas de Silenciamento de Genes , Regulação Neoplásica da Expressão Gênica/genética , Animais , Camundongos , Camundongos Endogâmicos BALB C , Feminino , XenoenxertosRESUMO
BACKGROUND: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22-150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. RESULTS: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. CONCLUSIONS: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.
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Lactação , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Animais , Bovinos/genética , Lactação/genética , Feminino , Splicing de RNA , Estudo de Associação Genômica Ampla , Perfilação da Expressão Gênica , Íntrons , TranscriptomaRESUMO
Drought stress is a common abiotic challenge that profoundly impacts plant growth and development. As sessile organisms, plants rely on various physiological and morphological adaptations to cope with drought conditions. The CIPK (calcineurin B-like protein-interacting protein kinase) family proteins play a pivotal role in mediating plant responses to abiotic stress through modulation of cellular membrane events via the CBL-CIPK complex. However, reports documenting the CIPKs' regulation of non-membrane events are scant. In this study, we discovered a novel subcellular localisation pattern of the AtCIPK20 protein of Arabidopsis, specifically to cortical microtubules (cMT), which is distinct from previously reported localisation patterns of plant CIPKs. AtCIPK20 regulates ABA-induced loss of cMT organisation in guard cells, thereby facilitating stomatal closure, mitigating leaf water loss, and protecting plants from drought stress in Arabidopsis. The C-terminal regulatory domain of AtCIPK20 governs its cMT targeting, whereas the interaction of AtCIPK20 with its CBL partners disrupts this localisation. Notably, the cMT targeting characteristic of AtCIPK20 is not exclusive, as several other CIPK members in Arabidopsis, maize, and rice exhibit similar localisation patterns. These findings broaden our current understanding of the role of plant CIPK members in abiotic stress resistance and suggest that future exploration of CIPK molecular functions should adopt a more comprehensive perspective.
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Strong metal-support interaction (SMSI) is widely proposed as a key factor in tuning catalytic performances. Herein, the classical SMSI between Au nanoparticles (NPs) and BiVO4 (BVO) supports (Au/BVO-SMSI) is discovered and used innovatively for photoelectrochemical (PEC) water splitting. Owing to the SMSI, the electrons transfer from V4+ to Au NPs, leading to the formation of electron-rich Au species (Auδ-) and strong electronic interaction (i.e., Auδ--Ov-V4+), which readily contributes to extract photogenerated holes and promote charge separation. Benefitted from the SMSI effect, the as-prepared Au/BVO-SMSI photoanode exhibits a superior photocurrent density of 6.25â mA cm-2 at 1.23â V versus the reversible hydrogen electrode after the deposition of FeOOH/NiOOH cocatalysts. This work provides a pioneering view for extending SMSI effect to bimetal oxide supports for PEC water splitting, and guides the interfacial electronic and geometric structure modulation of photoanodes consisting of metal NPs and reducible oxides for improved solar energy conversion efficiency.
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BACKGROUND: Folic acid is a water-soluble B vitamin (B9), which is closely related to the body's immune and other metabolic pathways. The folic acid synthesized by rumen microbes has been unable to meet the needs of high-yielding dairy cows. The incidence rate of subclinical mastitis in dairy herds worldwide ranged between 25%~65% with no obvious symptoms, but it significantly causes a decrease in lactation and milk quality. Therefore, this study aims at exploring the effects of folic acid supplementation on the expression profile of lncRNAs, exploring the molecular mechanism by which lncRNAs regulate immunity in subclinical mastitic dairy cows. RESULTS: The analysis identified a total of 4384 lncRNA transcripts. Subsequently, differentially expressed lncRNAs in the comparison of two groups (SF vs. SC, HF vs. HC) were identified to be 84 and 55 respectively. Furthermore, the weighted gene co-expression network analysis (WGCNA) and the KEGG enrichment analysis result showed that folic acid supplementation affects inflammation and immune response-related pathways. The two groups have few pathways in common. One important lncRNA MSTRG.11108.1 and its target genes (ICAM1, CCL3, CCL4, etc.) were involved in immune-related pathways. Finally, through integrated analysis of lncRNAs with GWAS data and animal QTL database, we found that differential lncRNA and its target genes could be significantly enriched in SNPs and QTLs related to somatic cell count (SCC) and mastitis, such as MSTRG.11108.1 and its target gene ICAM1, CXCL3, GRO1. CONCLUSIONS: For subclinical mastitic cows, folic acid supplementation can significantly affect the expression of immune-related pathway genes such as ICAM1 by regulating lncRNAs MSTRG.11108.1, thereby affecting related immune phenotypes. Our findings laid a ground foundation for theoretical and practical application for feeding folic acid supplementation in subclinical mastitic cows.
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Mastite Bovina , RNA Longo não Codificante , Feminino , Bovinos , Animais , Humanos , RNA Longo não Codificante/genética , Mastite Bovina/genética , Mastite Bovina/prevenção & controle , Ácido Fólico/farmacologia , Suplementos NutricionaisRESUMO
BACKGROUND: 5α-Hydroxycostic acid is a eudemane sesquiterpene that is isolated from the natural plant, Laggera alata. It exerts anti-inflammatory and anti-angiogenic effects on human breast cancer cells, but its role and underlying mechanism in choroidal neovascularization (CNV) are still unclear. We conducted a study to verify that 5α-Hydroxycostic acid can inhibit the formation and leakage of CNV, and describe the possible dual pathway by which it exerts its inhibitory effects in this process. METHODS: An in vitro model of choroidal neovascularization was established using VEGF164, while a rat model of choroidal neovascularization was established using a 532 nm laser. In both models, the effects of 5α-Hydroxycostic acid in vivo and in vitro were evaluated to determine its inhibitory effect on abnormal cell proliferation, migration and tubule formation, as well as its effect on pathological changes in choroidal tissues and the area of neovascularization leakage in rats. The levels of components in the VEGF/VEGFR and Ang2/Tie2 signaling pathways were measured in tissues and cells. RESULTS: In vitro experiments have shown that 5α-Hydroxycostic acid can inhibit abnormal cell proliferation, migration and angiogenesis. Additionally, 5α-Hydroxycostic acid enhances cell adhesion by inhibiting the phosphorylation pathways of VEGFR2 and Tie2. In vivo experiments demonstrated that 5α-Hydroxycostic acid has a positive therapeutic effect on choroidal neovascularization in rats. It can effectively reduce vascular leakage, consistent with the results of the cell experiments. CONCLUSION: 5α-Hydroxycostic acid can inhibit choroidal neovascularization by interfering with the VEGF- and Ang2/Tie2-related pathways, and it may be a good candidate drug for treating CNV.
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Neovascularização de Coroide , Fator A de Crescimento do Endotélio Vascular , Ratos , Humanos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Angiopoietina-2 , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Transdução de Sinais , Modelos Animais de DoençasRESUMO
Spring viremia of carp virus (SVCV) is strongly contagious and pathogenic to common carp and cyprinoid species. However, knowledge of how SVCV enters host cells is still inadequate. In this study, mass spectrometry (MS) was incorporated with tandem affinity purification (TAP) to identify host proteins that interact with SVCV glycoprotein, the main attachment protein of SVCV. Specifically, prohibitin (PHB) received the utmost attention from all the candidate proteins, and its interaction with the SVCV-G protein was confirmed by immunoprecipitation and immunofluorescence assays. Treatment with PHB-specific inhibitors or knockdown of the expression of PHB by siRNAs resulted in a marked reduction in binding and entry of SVCV on host cells, while overexpression of PHB increased SVCV attachment and invasion. Furthermore, binding of SVCV to ZF4 and FHM cells was inhibited by pre-incubating the virus with recombinant PHB protein (rPHB) or blocking the cell surface PHB with its polyclonal antibodies. In addition, overexpression of PHB on SVCV-nonpermissive Grouper spleen cells (GSs) conferred susceptibility to SVCV infection. In vivo, treatment of rPHB could significantly inhibit SVCV propagation within zebrafish and benefit the survival rate of SVCV-infected zebrafish. These results demonstrate that PHB plays a crucial role in both the attachment and entry stages of SVCV infection.
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Carpas , Doenças dos Peixes , Infecções por Rhabdoviridae , Rhabdoviridae , Animais , Carpas/genética , Peixe-Zebra , Viremia , ProibitinasRESUMO
In soybeans (Glycine max (L.) Merr.), their growth periods, DSF (days of sowing-to-flowering), and DFM (days of flowering-to-maturity) are determined by their required accumulative day-length (ADL) and active temperature (AAT). A sample of 354 soybean varieties from five world eco-regions was tested in four seasons in Nanjing, China. The ADL and AAT of DSF and DFM were calculated from daily day-lengths and temperatures provided by the Nanjing Meteorological Bureau. The improved restricted two-stage multi-locus genome-wide association study using gene-allele sequences as markers (coded GASM-RTM-GWAS) was performed. (i) For DSF and its related ADLDSF and AATDSF, 130-141 genes with 384-406 alleles were explored, and for DFM and its related ADLDFM and AATDFM, 124-135 genes with 362-384 alleles were explored, in a total of six gene-allele systems. DSF shared more ADL and AAT contributions than DFM. (ii) Comparisons between the eco-region gene-allele submatrices indicated that the genetic adaptation from the origin to the geographic sub-regions was characterized by allele emergence (mutation), while genetic expansion from primary maturity group (MG)-sets to early/late MG-sets featured allele exclusion (selection) without allele emergence in addition to inheritance (migration). (iii) Optimal crosses with transgressive segregations in both directions were predicted and recommended for breeding purposes, indicating that allele recombination in soybean is an important evolutionary drive. (iv) Genes of the six traits were mostly trait-specific involved in four categories of 10 groups of biological functions. GASM-RTM-GWAS showed potential in detecting directly causal genes with their alleles, identifying differential trait evolutionary drives, predicting recombination breeding potentials, and revealing population gene networks.
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Estudo de Associação Genômica Ampla , Glycine max , Glycine max/genética , Alelos , Desequilíbrio de Ligação , Locos de Características Quantitativas , Melhoramento Vegetal , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Soybean (Glycine max (L.) Merr.) has been disseminated globally as a photoperiod/temperature-sensitive crop with extremely diverse days to flowering (DTF) and days to maturity (DTM) values. A population with 371 global varieties covering 13 geographic regions and 13 maturity groups (MGs) was analyzed for its DTF and DTM QTL-allele constitution using restricted two-stage multi-locus genome-wide association study (RTM-GWAS). Genotypes with 20 701 genome-wide SNPLDBs (single-nucleotide polymorphism linkage disequilibrium blocks) containing 55 404 haplotypes were observed, and 52 DTF QTLs and 59 DTM QTLs (including 29 and 21 new ones) with 241 and 246 alleles (two to 13 per locus) were detected, explaining 84.8% and 74.4% of the phenotypic variance, respectively. The QTL-allele matrix characterized with all QTL-allele information of each variety in the global population was established and subsequently separated into geographic and MG set submatrices. Direct comparisons among them revealed that the genetic adaptation from the origin to geographic subpopulations was characterized by new allele/new locus emergence (mutation) but little allele exclusion (selection), while that from the primary MG set to emerged early and late MG sets was characterized by allele exclusion without allele emergence. The evolutionary changes involved mainly 72 DTF and 71 DTM alleles on 28 respective loci, 10-12 loci each with three to six alleles being most active. Further recombination potential for faster maturation (12-21 days) or slower maturation (14-56 days) supported allele convergence (recombination) as a constant genetic factor in addition to migration (inheritance). From the QTLs, 44 DTF and 36 DTM candidate genes were annotated and grouped respectively into nine biological processes, indicating multi-functional DTF/DTM genes are involved in a complex gene network. In summary, we identified QTL-alleles relatively thoroughly using RTM-GWAS for direct matrix comparisons and subsequent analysis.
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Adaptação Fisiológica/genética , Glycine max/crescimento & desenvolvimento , Glycine max/genética , Locos de Características Quantitativas , Proteínas de Soja/genética , Alelos , Evolução Biológica , Flores/genética , Flores/fisiologia , Ontologia Genética , Estudo de Associação Genômica Ampla , Haplótipos , Desequilíbrio de Ligação , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Proteínas de Soja/metabolismoRESUMO
Spring viraemia of carp virus (SVCV) is a fierce pathogen causing high mortality in the common carp. At present, the treatment of spring viraemia of carp (SVC) is limited. Innate immunity is the host's first line of defense against microbial pathogens. Retinoic acid-inducible gene I (RIG-I) activation plays an essential role in the antiviral immune response. Virus infection can activate the RIG-I signaling and induce the production of interferon (IFN) and the expression of IFN-stimulated genes (ISGs). STUB1 (STIP1 homology and U-box containing protein 1) is a highly conserved cytoplasmic protein. This protein is known to exist widely in many biological systems and plays an important role in the process of immune regulation, but little is known in fish. To explore the immune function of STUB1 in fish, STUB1 gene was cloned from zebrafish and analyzed in this study. Zebrafish STUB1 showed 77% and 79% amino acid sequence homology with those from human and mouse, respectively. The amino acid sequence of zebrafish STUB1 contains three TPR domains and one U-box domain. Subcellular localization study revealed that STUB1 is located in the cytoplasm. And overexpression of zebrafish STUB1 resulted in the activation of the transcription of IFN1 and ISGs. Functional analysis showed that STUB1 was able to activate RIG-I signaling, and promote the expression of RIG-I, but STUB1 can degrade RIG-I in mammals. The proliferation of SVCV was significantly inhibited after the overexpression of STUB1 and N-terminal TPR domain of STUB1 in EPC cells. And through secondary structure analysis, overexpression of the mutant of STUB1 110 amino acid resulted in weakened antiviral ability. The expression of STUB1 was attenuated by poly(I:C) treatment and SVCV infection. In summary, this study demonstrated for the first time that STUB1 can induce the production of IFN, enhance the expression of ISGs by promoting the expression of RIG-I and inhibiting viral replication in fish. These findings may form the essential basis for the development of antiviral targets and drugs.
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Carpas , Rhabdoviridae , Animais , Antivirais/metabolismo , Antivirais/farmacologia , Carpas/metabolismo , Imunidade Inata/genética , Mamíferos/metabolismo , Camundongos , Rhabdoviridae/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Antimicrobial peptides (AMPs) and their mimics are rapidly gaining attention as a new class of antimicrobials due to their clinical potential. AMPs are widely distributed throughout nature and participate in the innate host defense. In this study, 18 AMPs, including 3 ß-defensins, 3 hepcidins, 4 liver-expressed antimicrobial peptide 2 (LEAP-2) compounds, 4 g-type lysozymes, 2 c-type lysozymes, and 2 NK-lysins, were identified from the genome of Carassius auratus by a homologous search and were further classified based on their fundamental structural features and molecular phylogeny. C. auratus AMPs were found to be ubiquitously distributed in all tested tissues and showed similar expression profiles, with the exception of ß-defensins, when RT-qPCR was used to investigate the tissue distribution of AMPs in healthy Carassius gibel. In addition, the expression levels of NK-lysin genes in the tested tissues tended to be upregulated upon bacterial and viral infection when representative NK-lysins were chosen to examine their relative expression levels in various tissues. Importantly, the synthetic peptide caNKL2102-119, which targets the functional domain of saposin B in caNK-lysins, could effectively counter Aeromonas hydrophila, Staphylococcus aureus, and Escherichia coli with minimum inhibitory concentration (MIC) values of 3-6 µg/mL, as well as inhibit the proliferation of spring viraemia of carp virus (SVCV). These results provide potential targets for antibiotic-free breeding in the aquaculture industry.
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Peptídeos Antimicrobianos , Doenças dos Peixes , Proteínas de Peixes , Carpa Dourada , beta-Defensinas , Animais , Anti-Infecciosos , Peptídeos Antimicrobianos/genética , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Carpa Dourada/genética , Carpa Dourada/imunologia , beta-Defensinas/genéticaRESUMO
Lysozymes, acting as antimicrobial molecules, play a vital role in the host's innate immune response to pathogen infections. In the present study, a g-type lysozyme gene termed Tf-LyzG from roughskin sculpin, Trachidermus fasciatus was firstly reported. The deduced amino acid sequence of Tf-LyzG contained 188 residues and possessed conserved catalytic residues (Glu71, Asp84, and Asp95). Gene expression analysis revealed that Tf-LyzG was widely distributed in the tested eleven tissues with the highest expression in the gill and could be significantly induced post lipopolysaccharide (LPS) challenge. The lysozyme activity of the purified recombinant protein (rTf-LyzG) was found to be most active at pH 5.5 and 37 °C. rTf-LyzG exhibited a wide spectrum of potent bacteriolytic activity against four Gram-positive bacteria and six Gram-negative bacteria. It also displayed a high affinity to polysaccharides on bacteria surfaces including LPS, lipoteichoic acid (LTA), and peptidoglycan (PGN). rTf-LyzG was capable of binding and agglutinating all nine bacteria. Flow cytometry assay further revealed that rTf-LyzG could disrupt the membrane of Micrococcus lysodeikticus which is confirmed by scanning electron microscope (SEM) analysis that reveals blebs around the bacterial cell membrane. In summary, these data indicate that Tf-LyzG is of great importance in the fish immune response against pathogens invasion.
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Muramidase , Perciformes , Animais , Antibacterianos , Sequência de Bases , Gansos/genética , Gansos/metabolismo , Imunidade Inata/genética , Lipopolissacarídeos/farmacologia , FilogeniaRESUMO
Transcriptional programs regulated by the NF-κB family are essential for the inflammatory response as well as for innate and adaptive immunity. NF-κB activation occurs via two major signaling pathways: the canonical and the noncanonical. The canonical NF-κB pathway responds to diverse immune stimulations and leads to rapid but transient activation. As a member of the canonical NF-κB family, p65 is thought to be a key regulator of viral infection. Because of the embryonic lethality of p65-null mice, the physiological role of p65 in the antiviral immune response is still unclear. In this study, we generated p65-null zebrafish, which were viable and indistinguishable from their wildtype (WT) siblings under normal conditions. However, p65-null zebrafish were more sensitive to spring viremia of carp virus infection than their WT siblings. Further assays indicated that proinflammatory and antiviral genes, including IFN, were downregulated in p65-null zebrafish after spring viremia of carp virus infection compared with their WT siblings. Our results thus suggested that p65 is required for the antiviral response, activating not only proinflammatory genes but also antiviral genes (including IFN).
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Doenças dos Peixes/metabolismo , Proteínas de Peixes/metabolismo , NF-kappa B/metabolismo , Infecções por Rhabdoviridae/imunologia , Rhabdoviridae/fisiologia , Peixe-Zebra/imunologia , eIF-2 Quinase/metabolismo , Imunidade Adaptativa , Animais , Animais Geneticamente Modificados , Células Cultivadas , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Técnicas de Silenciamento de Genes , Imunidade Inata , Inflamação/genética , Interferons/genética , Camundongos , Transdução de Sinais , Peixe-Zebra/virologia , eIF-2 Quinase/genéticaRESUMO
Type I IFN mediates the innate immune system to provide defense against viral infections. NF-κB-inducing kinase (NIK) potentiates the basal activation of endogenous STING, which facilitates the recruitment of TBK1 with the ectopically expressed IRF3 to induce IFN production. Moreover, NIK phosphorylates IKKα and confers its ability to phosphorylate p100 (also known as NF-κB2) in mammals. Our study demonstrated that NIK plays a critical role in IFN production in teleost fish. It was found that NIK interacts with IKKα in the cytoplasm and that IKKα phosphorylates the NIK at the residue Thr432, which is different from the mammals. Overexpression of NIK caused the activation of IRF3 and NF-κB, which in turn led to the production of IFN and IFN-stimulated genes (ISGs). Furthermore, the ectopic expression of NIK was observed to be associated with a reduced replication of the fish virus, whereas silencing of endogenous NIK had an opposite effect in vitro. Furthermore, NIK knockdown significantly reduced the expression of IFN and key ISGs in zebrafish larvae after spring viremia of carp virus infection. Additionally, the replication of spring viremia of carp virus was enhanced in NIK knockdown zebrafish larvae, leading to a lower survival rate. In summary, our findings revealed a previously undescribed function of NIK in activating IFN and ISGs as a host antiviral response. These findings may facilitate the establishment of antiviral therapy to combat fish viruses.
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Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/metabolismo , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Carpas/metabolismo , Carpas/virologia , Linhagem Celular , Quinase I-kappa B/metabolismo , Viremia/metabolismo , Viremia/virologia , Peixe-Zebra , Quinase Induzida por NF-kappaBRESUMO
RNA polymerase II is one of the most vital macromolecular complexes in eukaryotes and the assembly of such complete enzyme requires many factors. Three members of GPN-loop GTPase family Npa3/Gpn1, Gpn2, and Gpn3 participate in the biogenesis of RNA polymerase II with nonredundant roles. We show here that rapid degradation of each GPN protein in yeast leads to cytoplasmic accumulation of Rpb1 and defects in the assembly of RNA polymerase II, suggesting conserved functions of GPN paralogs for RNA polymerase II biogenesis as in humans. Taking advantage of a multicopy genetic screening, we identified GPN3 and assembly factor RBA50 among others as strong suppressors of npa3ts mutants. We further demonstrated that Npa3 interacts with Gpn3 and Rba50, similarly human Gpn1 physically interacts with Gpn3 and RPAP1 (human analog of Rba50). Moreover, a mutual dependency of protein levels of Npa3 and Gpn3 was also clearly presented in yeast using an auxin-inducible degron (AID) system. Interestingly, Rpb2, the second largest subunit of RNA polymerase II was determined to be the subunit that interacts with both Gpn1 and Rba50, indicating a close association of Npa3 and Rba50 in Rpb2 subcomplex assembly. Based on these results, we conclude that Npa3 interacts with Gpn3 and Rba50, for RNA polymerase II biogenesis. We therefore propose that multiple factors may coordinate through conserved regulatory mechanisms in the assembly of RNA polymerase complex.
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Proteínas de Transporte/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , RNA Polimerase II/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte/genética , Núcleo Celular/metabolismo , Citoplasma/metabolismo , GTP Fosfo-Hidrolases/genética , Proteínas de Ligação ao GTP/genética , Humanos , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Mutação , Ligação Proteica , RNA Polimerase II/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Risk and resilience assessment of disasters plays a critical role in decision making for emergency response and postdisaster recovery. Yet, there is still a lack of modeling framework that could capture the effectiveness of economic resilience under uncertain disaster conditions. The objective of this study is to develop a novel integrated framework that is able to help decisionmakers understand the effectiveness of resilience performance under various risk conditions. Using hazard data of the Bohai Sea and throughput data of the Port of Yingkou (China) as an example, the copula-modeling method was adopted for the risk assessment of sea ice disasters on seaport operations. This study shows that the Gumbel Copula method, with consideration of ice thickness level and area of ice cover, provides the most robust risk assessment outcome. In addition, a grid chart system with an overlap of a joint return period and port throughput change provides a straightforward understanding of resilience performance under different risk levels. In particular, economic resilience tactics, such as production recapture and effective management, were confirmed to be effective resilience strategies, especially when a risk level is high, as port operational losses can be avoided up to 86.8%. Overall, the study provides insights that could help stakeholders improve the effectiveness of disaster risk management through an improved understanding of the linkage between risk and resilience.
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The allotetraploid species Brassica juncea (mustard) is grown worldwide as oilseed and vegetable crops; the yellow seed-color trait is particularly important for oilseed crops. Here, to examine the factors affecting seed coat color, we performed a metabolic and transcriptomic analysis of yellow- and dark-seeded B. juncea seeds. In this study, we identified 236 compounds, including 31 phenolic acids, 47 flavonoids, 17 glucosinolates, 38 lipids, 69 other hydroxycinnamic acid compounds, and 34 novel unknown compounds. Of these, 36 compounds (especially epicatechin and its derivatives) accumulated significantly different levels during the development of yellow- and dark-seeded B. juncea. In addition, the transcript levels of BjuDFR, BjuANS,BjuBAN, BjuTT8, and BjuTT19 were closely associated with changes to epicatechin and its derivatives during seed development, implicating this pathway in the seed coat color determinant in B. juncea. Furthermore, we found numerous variations of sequences in the TT8A genes that may be associated with the stability of seed coat color in B. rapa, B. napus, and B. juncea, which might have undergone functional differentiation during polyploidization in the Brassica species. The results provide valuable information for understanding the accumulation of metabolites in the seed coat color of B. juncea and lay a foundation for exploring the underlying mechanism.
Assuntos
Mostardeira/genética , Mostardeira/metabolismo , Catequina/análogos & derivados , Catequina/metabolismo , Flavonoides/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Glucosinolatos/metabolismo , Metaboloma , Mostardeira/crescimento & desenvolvimento , Fenótipo , Pigmentação/genética , Sementes/genética , Sementes/metabolismoRESUMO
OBJECTIVE: To investigate the relationship between baseline characteristics and 90-day mortality in hepatitis B virus-related acute-on-chronic liver failure patients. METHODS: The retrospective study was conducted at Fuling Centre Hospital, Chongqing, China, and comprised data from July 2015 to June 2018 of hepatitis B virus-related acute-on-chronic liver failure patients. Demographic characteristics and clinical features at admission and 7 days post-admission were noted. The data was then divided into two groups based on a patient's 90-day survival status, and their clinical and lab characteristics were compared using SPSS 16. RESULTS: Of the 120 patients screened, 100(83.3%) were included; 75(75%) males and 25(25%) females. The overall mean age was 50.04±14.61 years. There were 68(68%) in the surviving group and 32(32%) in the non-surviving group. Patients who had hyper-leukocytosis, hypoalbuminaemia, lower prothrombin time activity, ascites, hepatic encephalopathy, higher alanine aminotransferase levels and renal dysfunction at admission had poor prognoses (p<0.05). At 7 days post-admission, the non-surviving group had lower platelet count, higher aspartate aminotransferase level, lower bilirubin normalisation rate and higher total bile acid levels (p<0.05). CONCLUSIONS: Baseline organ failure severity was found to determine the outcome more strongly than the underlying cause.
Assuntos
Insuficiência Hepática Crônica Agudizada , Hepatite B Crônica , Hepatite B , Adulto , Bilirrubina , China/epidemiologia , Feminino , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Long non-coding RNA (lncRNA) is a class of non-coding RNAs with a length greater than 200 nucleotides. Although lncRNAs do not have any protein coding capability, they can affect the phenotypes of traits by influencing gene expression through transcriptional regulation, post-transcriptional regulation, and epigenetic modification. In modern animal husbandry production, besides increasing growth and yield traits, investigations on the regulation mechanisms of immune factors, cytokines and other disease resistance-related indicators and traits are particularly important for improving the health and welfare of domesticated animals as well as public health. In recent years, researchers have made significant progress in understanding the regulatory mechanisms of lncRNA on the disease resistance traits of chickens (Gallus gallus), pigs (Sus scrofa), cattle (Bos taurus) and other important domesticated animals, thereby laying the basic foundation for the translational application of epigenetic markers in breeding of animals with disease resistance. In this review, we briefly introduce the biological functions and the origins of lncRNAs, then focus on the research progress on the regulatory effects of lncRNAs on disease resistance traits of domesticated animals, and thus providing the scientific basis for the research of lncRNA and its application in the breeding of disease-resistant animals.