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To fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.
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Bases de Dados Genéticas , Suínos , Animais , Estudo de Associação Genômica Ampla , Genótipo , Herança Multifatorial , Fenótipo , Suínos/genética , MultiômicaRESUMO
Studies have suggested that microglial IL-6 modulates inflammatory pain; however, the exact mechanism of action remains unclear. We therefore hypothesized that PKCε and MEG2 competitively bind to STAT3 and contribute to IL-6-mediated microglial hyperalgesia during inflammatory pain. Freund's complete adjuvant (FCA) and lipopolysaccharide (LPS) were used to induce hyperalgesia model mice and microglial inflammation. Mechanical allodynia was evaluated using von Frey tests in vivo. The interaction among PKCε, MEG2, and STAT3 was determined using ELISA and immunoprecipitation assay in vitro. The PKCε, MEG2, t-STAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, GLUT3, and TREM2 were assessed by Western blot. IL-6 promoter activity and IL-6 concentration were examined using dual luciferase assays and ELISA. Overexpression of PKCε and MEG2 promoted and attenuated inflammatory pain, accompanied by an increase and decrease in IL-6 expression, respectively. PKCε displayed a stronger binding ability to STAT3 when competing with MEG2. STAT3Ser727 phosphorylation increased STAT3 interaction with both PKCε and MEG2. Moreover, LPS increased PKCε, MEG2, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and GLUT3 levels and decreased TREM2 during microglia inflammation. IL-6 promoter activity was enhanced or inhibited by PKCε or MEG2 in the presence of STAT3 and LPS stimulation, respectively. In microglia, overexpression of PKCε and/or MEG2 resulted in the elevation of tSTAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and TREM2, and the reduction of GLUT3. PKCε is more potent than MEG2 when competitively binding to STAT3, displaying dual modulatory effects of IL-6 production, thus regulating the GLUT3 and TREM2 in microglia during inflammatory pain sensation.
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Hiperalgesia , Inflamação , Interleucina-6 , Microglia , Proteína Quinase C-épsilon , Fator de Transcrição STAT3 , Animais , Masculino , Camundongos , Adjuvante de Freund , Hiperalgesia/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Dor/metabolismo , Fosforilação , Ligação Proteica , Proteína Quinase C-épsilon/metabolismo , Proteína Quinase C-épsilon/genética , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Fator de Transcrição STAT3/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismoRESUMO
BACKGROUND: The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation. METHODS: Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on oral bacteria proliferation activity was investigated in vitro. RESULTS: Taxon-based analysis indicated that PPI administration increased Streptococcus abundance in gut microbiota (P<0.001), and the increased species of Streptococcus were found to be from the oral site or oral/nasal sites, in which Streptococcus anginosus was identified as the significantly changed species (P<0.004). Microbial source tracker revealed that PPI significantly increased the contribution of oral bacteria to gut microbiota (P=0.026), and no significant difference was found in PM group (P=0.467). Compared to the baseline, there was a 42-fold increase in gut abundance of Streptococcus anginosus in PP group (P=0.002), and the times decreased to 16-fold in PM group (P=0.029). Mouse models showed that combination of PPI and Streptococcus anginosus significantly increased the gut abundance of Streptococcus anginosus compared with using PPI or Streptococcus anginosus only. Furthermore, Streptococcus anginosus cannot survive in vitro at a pH lower than 5. CONCLUSIONS: PPIs altered gut microbiota by promoting oral-originated Streptococcus translocation into gut.
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Esomeprazol , Fezes , Microbioma Gastrointestinal , Inibidores da Bomba de Prótons , Saliva , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Adulto Jovem , Translocação Bacteriana/efeitos dos fármacos , Clorexidina/farmacologia , Esomeprazol/farmacologia , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Voluntários Saudáveis , Concentração de Íons de Hidrogênio , Boca/microbiologia , Antissépticos Bucais/farmacologia , Estudos Prospectivos , Inibidores da Bomba de Prótons/farmacologia , RNA Ribossômico 16S , Saliva/microbiologia , Streptococcus anginosus/efeitos dos fármacos , Streptococcus anginosus/isolamento & purificaçãoRESUMO
Increasing planting density is one of the most effective ways to improve crop yield. However, one major factor that limits crop planting density is the weakened immunity of plants to pathogens and insects caused by dim light (DL) under shade conditions. The molecular mechanism underlying how DL compromises plant immunity remains unclear. Here, we report that DL reduces rice (Oryza sativa) resistance against brown planthopper (BPH; Nilaparvata lugens) by elevating ethylene (ET) biosynthesis and signaling in a Phytochrome B (OsPHYB)-dependent manner. The DL-reduced BPH resistance is relieved in osphyB mutants, but aggravated in OsPHYB overexpressing plants. Further, we found that DL reduces the nuclear accumulation of OsphyB, thus alleviating Phytochrome Interacting Factor Like14 (OsPIL14) degradation, consequently leading to the up-regulation of 1-Aminocyclopropane-1-Carboxylate Oxidase1 (OsACO1) and an increase in ET levels. In addition, we found that nuclear OsphyB stabilizes Ethylene Insensitive Like2 (OsEIL2) by competitively interacting with EIN3 Binding F-Box Protein (OsEBF1) to enhance ET signaling in rice, which contrasts with previous findings that phyB blocks ET signaling by facilitating Ethylene Insensitive3 (EIN3) degradation in other plant species. Thus, enhanced ET biosynthesis and signaling reduces BPH resistance under DL conditions. Our findings provide insights into the molecular mechanism of the light-regulated ET pathway and host-insect interactions and potential strategies for sustainable insect management.
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Etilenos , Hemípteros , Oryza , Fitocromo B , Animais , Etilenos/metabolismo , Hemípteros/metabolismo , Oryza/metabolismo , Fitocromo B/genética , Fitocromo B/metabolismoRESUMO
One of the functions of organism cells is to maintain energy homeostasis to promote metabolism and adapt to the environment. The 3 major pathways of cellular energy metabolism are glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS). Neurons, astrocytes, and microglia are crucial in allodynia, hyperalgesia, and sensitization in nociceptive pathways. This review focused on these 3 major cellular energy metabolism pathways, aiming to elucidate the relationship between neurocyte and pain sensation and present the reprogramming of energy metabolism on pain, as well as the cellular and molecular mechanism underlying various forms of pain. The clinical and preclinical drugs involved in pain treatment and molecular mechanisms via cellular energy metabolism were also discussed.
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BACKGROUND: Pulmonary fibromatosis (PF) is a specific variant of fibromatosis, which is rarely reported occurring in the lung. PF with HIPK2-YAP1 fusion was a novel entity. CASE PRESENTATION: In this report, a 66-year-old male with PF had been smoking over 40 years. Multiple cords and small nodules in both lungs had been detected in a health examination two years earlier at our hospital. But approximately twofold enlarged in the lingual segment of the upper lobe in the left lung were disclosed in this year. Immunohistochemical analysis demonstrated that the vimentin and ß-Catenin were positive in the largest nodule. After underwent a DNA/RNA panel next-generation sequencing (NGS), missense mutations and HIPK2-YAP1 fusion were found in this sample. Ultimately, the case diagnosis as PF with HIPK2-YAP1 fusion after multidisciplinary treatment. Currently, the patient is doing well and recurrence-free at 14 months post-surgery. CONCLUSIONS: It's difficult for patients with complex morphology to make accurate diagnosis solely based on morphology and immunohistochemistry. But molecular detection is an effective method for further determining pathological subtypes.
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Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte , Neoplasias Pulmonares , Proteínas Serina-Treonina Quinases , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Masculino , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Mutação de Sentido IncorretoRESUMO
High-precision mapping based on portable X-ray fluorescence (PXRF) data is currently being studied extensively; however, owing to poor correlation with soil metal concentration, the original PXRF data directly used for co-kriging interpolation (CKI) cannot accurately map contaminated sites with heterogeneous concentrations. Therefore, this study selected a landfill-contaminated site for research, explored the best correlation mode between PXRF variants and actual heavy metal concentration, analyzed the impact of improving the correlation model on the CKI of the spatial distribution of heavy metals, and explored the most appropriate CKI mode and point density. The results showed the following: (1) After nonlinear transformation, the correlation model between PXRF and the actual concentration was significantly improved, and the correlation coefficients of five heavy metals increased from 0.214-0.232 to 0.936-0.986. (2) The introduction of corrected PXRF data significantly improves the accuracy of CKI. Compared with the original PXRF co-kriging interpolation (OP-CKI), the ME of the corrected PXRF co-kriging interpolation (CP-CKI) for Zn, Pb, and Cu decreased by 78.2 %, 45.5 %, and 65.3 %, respectively. In terms of the spatial distribution of heavy metal pollutant concentrations, CP-CKI effectively improved the influence of local anomalous high-value points on the interpolation accuracy. (3) When the sample density measured by inductively coupled plasma mass spectrometry (ICP-MS) was less than 4 boreholes/hm2, CKI accuracy decreased significantly, indicating that the sample density should not be less than a certain threshold during CKI. (4) When the sample density measured by PXRF exceeded 7 boreholes/hm2, the mean error and root mean square error of CKI continued to decrease, suggesting that the introduction of enough sample density measured by PXRF can effectively improve the accuracy of CKI.
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Metais Pesados , Poluentes do Solo , Raios X , Espectrometria por Raios X/métodos , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Análise Espacial , Solo/químicaRESUMO
The domestic pig (Sus scrofa) and its subfamilies have experienced long-term and extensive gene flow, particularly in Southeast Asia. Here, we analyzed 236 pigs, focusing on Yunnan indigenous, European commercial, East Asian, and Southeast Asian breeds, using the Pig Genomics Reference Panel (PGRP v1) of Pig Genotype-Tissue Expression (PigGTEx) to investigate gene flow and associated complex traits by integrating multiple database resources. In this study, we discovered evidence of admixtures from European pigs into the genome of Yunnan indigenous pigs. Additionally, we hypothesized that a potential conceptual gene flow route that may have contributed to the genetic composition of the Diannan small-ear pig is a gene exchange from the Vietnamese pig. Based on the most stringent gene introgression scan using the fd statistic, we identified three specific loci on chromosome 8, ranging from 51.65 to 52.45 Mb, which exhibited strong signatures of selection and harbored the NAF1, NPY1R, and NPY5R genes. These genes are associated with complex traits, such as fat mass, immunity, and litter weight, in pigs, as supported by multiple bio-functionalization databases. We utilized multiple databases to explore the potential dynamics of genetic exchange in Southeast Asian pig populations and elucidated specific gene functionalities.
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Fluxo Gênico , Animais , Sudeste Asiático , Suínos/genética , Bases de Dados Genéticas , Sus scrofa/genética , Genética Populacional , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Genótipo , Cruzamento , População do Sudeste AsiáticoRESUMO
The physical and chemical characteristics of fly ash has changed significantly under ultra-low emission system and the current leaching system is no longer suitable for high alkalinity fly ash. This work investigated the pH values and evolution of physical and chemical characteristics of fly ash from 24 typical municipal solid waste incineration plants in China. The pH value of the leaching solution obtained by HJ/T 300-2007 presented two different acid and alkali characteristics, where high and low alkalinity fly ash accounted for 54.17% and 45.83%, respectively. The alkali content in fly ash increased significantly after ultra-low emission standard, increasing by 18.24% compared with before the implementation of GB 18485-2014. The leaching behavior of high alkalinity fly ash showed the illusion that they could enter the landfill only by the addition of a small amount of chelating agent or even without stabilization treatment, and its long-term landfill risk is significant. The phase change of high alkalinity fly ash and pH value change of the leaching solution after carbonation were the key factors for the leaching concentration change of heavy metals. Therefore, it is recommended to improve the existing leaching system or conduct accelerated carbonization experiments to scientifically evaluate the long-term leaching characteristics of high alkalinity fly ash, and to reduce the risk of heavy metal release from high alkalinity FA after entering the landfill site.
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Cinza de Carvão , Incineração , Resíduos Sólidos , Cinza de Carvão/análise , Cinza de Carvão/química , Resíduos Sólidos/análise , China , Metais Pesados/análise , Concentração de Íons de Hidrogênio , Eliminação de ResíduosRESUMO
Layer-by-layer (LbL) deposition of active layers in organic solar cells (OSCs) offers immense potential for optimizing performance through precise tailoring of each layer. However, achieving high-performance LbL OSCs with distinct solid additives in each layer remains challenging. In this study, we explore a novel approach that strategically incorporates different solid additives into specific layers of LbL devices. To this end, we introduce FeCl3 into the lower donor (D18) layer as a p-type dopant to enhance hole concentration and mobility. Concurrently, we incorporate the wide-band gap conjugated polymer poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) into the upper acceptor (L8-BO) layer to improve the morphology and prolong exciton lifetime. Unlike previous studies, our approach combines these two strategies to achieve higher and more balanced electron and hole mobility without affecting device open-circuit voltage, while also suppressing charge recombination. Consequently, the power conversion efficiency (PCE) of the D18+FeCl3/L8-BO device increases to 18.12 %, while the D18/L8-BO+PFO device attains a PCE of 18.79 %. These values represent substantial improvements over the control device's PCE of 17.59 %. Notably, when both FeCl3 and PFO are incorporated, the D18+FeCl3/L8-BO+PFO device achieves a remarkable PCE of 19.17 %. In summary, our research results demonstrate the effectiveness of the layered solid additive strategy in improving OSC performance.
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BACKGROUND: Chinese indigenous pigs in Yunnan exhibit considerable phenotypic diversity, but their population structure and the biological interpretation of signatures of artificial selection require further investigation. To uncover population genetic diversity, migration events, and artificial selection signatures in Chinese domestic pigs, we sampled 111 Yunnan pigs from four breeds in Yunnan which is considered to be one of the centres of livestock domestication in China, and genotyped them using Illumina Porcine SNP60K BeadChip. We then leveraged multiple bioinformatics database tools to further investigate the signatures and associated complex traits. RESULTS: Population structure and migration analyses showed that Diannanxiaoer pigs had different genetic backgrounds from other Yunnan pigs, and Gaoligongshan may undergone the migration events from Baoshan and Saba pigs. Intriguingly, we identified a possible common target of sharing artificial selection on a 265.09 kb region on chromosome 5 in Yunnan indigenous pigs, and the genes on this region were associated with cardiovascular and immune systems. We also detected several candidate genes correlated with dietary adaptation, body size (e.g., PASCIN1, GRM4, ITPR2), and reproductive performance. In addition, the breed-sharing gene MMP16 was identified to be a human-mediated gene. Multiple lines of evidence at the mammalian genome, transcriptome, and phenome levels further supported the evidence for the causality between MMP16 variants and the metabolic diseases, brain development, and cartilage tissues in Chinese pigs. Our results suggested that the suppression of MMP16 would directly lead to inactivity and insensitivity of neuronal activity and skeletal development in Chinese indigenous pigs. CONCLUSION: In this study, the population genetic analyses and identification of artificial selection signatures of Yunnan indigenous pigs help to build an understanding of the effect of human-mediated selection mechanisms on phenotypic traits in Chinese indigenous pigs. Further studies are needed to fully characterize the process of human-mediated genes and biological mechanisms.
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Metaloproteinase 16 da Matriz , Sus scrofa , Humanos , Suínos/genética , Animais , Metaloproteinase 16 da Matriz/genética , China , Sus scrofa/genética , Genoma , Biologia Computacional , Seleção Genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
CRISPR-based directed evolution is an effective breeding biotechnology to improve agronomic traits in plants. However, its gene diversification is still limited using individual single guide RNA. We described here a multiplexed orthogonal base editor (MoBE), and a randomly multiplexed sgRNAs assembly strategy to maximize gene diversification. MoBE could induce efficiently orthogonal ABE (<36.6%), CBE (<36.0%), and A&CBE (<37.6%) on different targets, while the sgRNA assembling strategy randomized base editing events on various targets. With respective 130 and 84 targets from each strand of the 34th exon of rice acetyl-coenzyme A carboxylase (OsACC), we observed the target-scaffold combination types up to 27 294 in randomly dual and randomly triple sgRNA libraries. We further performed directed evolution of OsACC using MoBE and randomly dual sgRNA libraries in rice, and obtained single or linked mutations of stronger herbicide resistance. These strategies are useful for in situ directed evolution of functional genes and may accelerate trait improvement in rice.
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Edição de Genes , Oryza , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , Oryza/genética , Melhoramento VegetalRESUMO
BACKGROUND: Sepsis-associated encephalopathy (SAE) is characterized by diffuse brain dysfunction, long-term cognitive impairment, and increased morbidity and mortality. The current treatment for SAE is mainly symptomatic; the lack of specific treatment options and a poor understanding of the underlying mechanism of disease are responsible for poor patient outcomes. Fgr is a member of the Src family of tyrosine kinases and is involved in the innate immune response, hematologic cancer, diet-induced obesity, and hemorrhage-induced thalamic pain. This study investigated the protection provided by an Fgr kinase inhibitor in SAE and the underlying mechanism(s) of action. METHODS: A cecal ligation and puncture (CLP)-induced mouse sepsis model was established. Mice were treated with or without an Fgr inhibitor and a PGC-1α inhibitor/activator. An open field test, a novel object recognition test, and an elevated plus maze were used to assess neurobehavioral changes in the mice. Western blotting and immunofluorescence were used to measure protein expression, and mRNA levels were measured using quantitative PCR (qPCR). An enzyme-linked immunosorbent assay was performed to quantify inflammatory cytokines. Mitochondrial membrane potential and morphology were measured by JC-1, electron microscopy, and the MitoTracker Deep Red probe. Oxidative stress and mitochondrial dysfunction were analyzed. In addition, the regulatory effect of Fgr on sirtuin 1 (SIRT1) was assessed. RESULTS: CLP-induced sepsis increased the expression of Fgr in the hippocampal neurons. Pharmacological inhibition of Fgr attenuated CLP-induced neuroinflammation, the survival rate, cognitive and emotional dysfunction, oxidative stress, and mitochondrial dysfunction. Moreover, Fgr interacted with SIRT1 and reduced its activity and expression. In addition, activation of SIRT1/PGC-1α promoted the protective effects of the Fgr inhibitor on CLP-induced brain dysfunction, while inactivation of SIRT1/PGC-1α counteracted the benefits of the Fgr inhibitor. CONCLUSIONS: To our knowledge, this is the first report of Fgr kinase inhibition markedly ameliorating SAE through activation of the SIRT1/PGC-1α pathway, and this may be a promising therapeutic target for SAE.
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Antineoplásicos , Encefalopatia Associada a Sepse , Sepse , Camundongos , Animais , Encefalopatia Associada a Sepse/complicações , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Sirtuína 1/metabolismo , Doenças Neuroinflamatórias , Mitocôndrias/metabolismo , Estresse Oxidativo , Transdução de Sinais , Sepse/complicações , Sepse/tratamento farmacológico , Modelos Animais de Doenças , Antineoplásicos/farmacologiaRESUMO
The most important difference between ultrastrong and non-ultrastrong coupling regimes is that the ground state contains excitations. We consider a qubit-plasmon-phonon ultrastrong coupling (USC) system with a three-level atom coupled to the photon and phonon via its upper two energy levels and show that spontaneous emission of the atom from its intermediate to its ground state produces photon and phonon pairs. It is shown that the current system can produce a strong photon/phonon stream and the atom-phonon coupling plays the active role, which ensures the experimental detection. The emission spectrum and various high-order correlation functions confirm the generation of the pairs of photons and phonons. Our study has important implications for future research on virtual photon and phonon pairs creation in the ground state of the USC regime.
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Curcumin has anti-inflammatory, antioxidant, and anticancer effects and is used to treat diseases such as dermatological diseases, infection, stress, depression, and anxiety. J147, an analogue of curcumin, is designed and synthesized with better stability and bioavailability. Accumulating evidence demonstrates the potential role of J147 in the prevention and treatment of Alzheimer's disease, diabetic neuropathy, ischemic stroke, depression, anxiety, and fatty liver disease. In this narrative review, we summarized the background and biochemical properties of J147 and discussed the role and mechanism of J147 in different diseases. Overall, the mechanical attributes of J147 connote it as a potential target for the prevention and treatment of neurological diseases.
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Curcumina , Neuropatias Diabéticas , Humanos , Ansiedade , Transtornos de AnsiedadeRESUMO
BACKGROUND: Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces antinociception via glycolysis and mitochondria-related pathways is still unclear. METHODS: Right hind paw inflammatory pain in mice was induced by intraplantar injection of Freund's Complete Adjuvant (FCA). Von Frey test was then used to measure the paw withdrawal threshold. The detection of glycolysis and mitochondrial pathway-related proteins and IL-8 were determined by Western blot and ELISA. The potential interaction between Dexa and fructose-1,6-bisphosphate (FBP, a PKM2 activator) was examined by simulation predictions using molecular docking. RESULTS: Intrathecal administration of Dexa (20 µg/20 µL) had an obvious analgesic effect in FCA-treated mice, which was counteracted by the glycolysis inhibitor 2-deoxyglucose (2-DG, 5 mg/20 µL) or the mitochondria-related pathway inhibitor oligomycin complex (Oligo, 5 µg/20 µL). In the glycolysis pathway, Dexa decreased GLUT3 and had no impact on HIF-1α expression during FCA-induced inflammation. Additionally, Dexa further increased the PKM2 level, accompanied by the formation of hydrogen bonds between Dexa and the PKM2 activator fructose-1,6-bisphosphate (FBP). In the mitochondrial pathway, Dexa downregulated the expression of Mfn2 protein but not the PGC-1α and SIRT-1 levels in the spinal cord. Moreover, both 2-DG and Oligo decreased Mfn2 expression. Finally, IL-8 level was reduced by the single or combined administration of Dexa, 2-DG, and Oligo. CONCLUSION: Dexa attenuated IL-8 expression via glycolysis and mitochondrial pathway-related proteins, thus mediating the analgesic effect during inflammatory pain.
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Frutose , Interleucina-8 , Animais , Camundongos , Simulação de Acoplamento Molecular , Glicólise , Mitocôndrias , Dexametasona/farmacologia , AnalgésicosRESUMO
Brown planthopper (BPH) is one of the most destructive insects affecting rice (Oryza sativa L.) production. Phenylalanine ammonia-lyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority of PALs in rice is significantly induced by BPH feeding. Knockdown of OsPALs significantly reduces BPH resistance, whereas overexpression of OsPAL8 in a susceptible rice cultivar significantly enhances its BPH resistance. We found that OsPALs mediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression of OsPAL6 and OsPAL8 in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice.
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Hemípteros/efeitos dos fármacos , Oryza/enzimologia , Oryza/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Fenilalanina Amônia-Liase/farmacologia , Doenças das Plantas/imunologia , Fatores de Transcrição/metabolismo , Animais , DNA de Plantas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Genes de Plantas , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/fisiologia , Lignina/metabolismo , Oryza/genética , Oryza/imunologia , Fenilalanina Amônia-Liase/genética , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Ácido Salicílico/metabolismoRESUMO
Plant defense responses against insect pests are intricately regulated by highly complex regulatory networks. Post-translational modifications (PTMs) of histones modulate the expression of genes involved in various biological processes. However, the role of PTMs in conferring insect resistance remains unclear. Through the screening of a T-DNA insertion activation-tagged mutant collection in rice, we identified the mutant planthopper susceptible 1 (phs1), which exhibits heightened expression of SET domain group 703 (SDG703). This overexpression is associated with increased susceptibility to the small brown planthopper (SBPH), an economically significant insect pest affecting rice crops. SDG703 is constitutively expressed in multiple tissues and shows substantial upregulation in response to SBPH feeding. SDG703 demonstrates the activity of histone H3K9 methyltransferase. Transcriptomic analysis revealed the downregulation of genes involved in effector-triggered immunity (ETI) and pattern-triggered immunity (PTI) in plants overexpressing SDG703. Among the downregulated genes, the overexpression of SDG703 in plants resulted in a higher level of histone H3K9 methylation compared to control plants. Collectively, these findings indicate that SDG703 suppresses the expression of defense-related genes through the promotion of histone methylation, consequently leading to reduced resistance against SBPH. The defense-related genes regulated by histone methylation present valuable targets for developing effective pest management strategies in future studies. Furthermore, our study provides novel insight into the epigenetic regulation involved in plant-insect resistance.
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Hemípteros , Oryza , Animais , Epigênese Genética , Histonas , Domínios PR-SET , Regulação para Baixo , Histona Metiltransferases , Oryza/genéticaRESUMO
Rice stripe virus (RSV) is one of the most destructive viral diseases affecting rice production. However, so far, only one RSV resistance gene has been cloned, the molecular mechanisms underlying host-RSV interaction are still poorly understood. Here, we show that increasing levels or signaling of brassinosteroids (BR) and jasmonic acid (JA) can significantly enhance the resistance against RSV. On the contrary, plants impaired in BR or JA signaling are more susceptible to RSV. Moreover, the enhancement of RSV resistance conferred by BR is impaired in OsMYC2 (a key positive regulator of JA response) knockout plants, suggesting that BR-mediated RSV resistance requires active JA pathway. In addition, we found that RSV infection suppresses the endogenous BR levels to increase the accumulation of OsGSK2, a key negative regulator of BR signaling. OsGSK2 physically interacts with OsMYC2, resulting in the degradation of OsMYC2 by phosphorylation and reduces JA-mediated defense to facilitate virus infection. These findings not only reveal a novel molecular mechanism mediating the crosstalk between BR and JA in response to virus infection and deepen our understanding about the interaction of virus and plants, but also suggest new effective means of breeding RSV resistant crops using genetic engineering.
Assuntos
Brassinosteroides/metabolismo , Ciclopentanos/metabolismo , Oryza , Oxilipinas/metabolismo , Plantas Geneticamente Modificadas , Transdução de Sinais , Tenuivirus , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Oryza/genética , Oryza/metabolismo , Oryza/virologia , Doenças das Plantas/genética , Doenças das Plantas/virologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/virologia , Tenuivirus/genética , Tenuivirus/metabolismoRESUMO
METHODS: A rat hyperalgesia model was induced using an intraplantar injection of Freund's complete adjuvant (FCA) or an intrathecal injection of IL-6. Mechanical allodynia was evaluated using von Frey filament tests after intrathecal injections of T-5224 (c-Fos/AP-1 inhibitor), minocycline (Mino, a specific microglia inhibitor), L-2-aminoadipic acid (LAA, an astroglial toxin), PKCε inhibitor peptide, APTSTAT3-9R (STAT3 inhibitor), or anti-IL-6 antibody. The c-Fos, GFAP, Iba-1, PKCε, STAT3, pSTAT3Tyr705 and pSTAT3Ser727, and IL-6 expression at the spinal cord level was assessed by Western blot analysis. The interactive effects of PKCε and STAT3 were determined using immunofluorescence staining and immunoprecipitation in vivo and in vitro. Interleukin-6 promoter activity was examined using luciferase assays. RESULTS: T-5224, Mino, and LAA attenuated FCA- or IL-6-mediated inflammatory pain, with a decrease in c-Fos, GFAP, Iba-1, PKCε, and IL-6 expression. PKCε inhibitor peptide and APTSTAT3-9R reversed FCA-induced nociceptive behavior, while decreasing pSTAT3Ser727, IL-6, c-Fos, GFAP, and Iba-1 expression and PKCε and STAT3 coexpression. Interleukin-6 promoter activity increased in the presence of PKCε and STAT3. The interaction with PKCε increased on phosphorylating STAT3 at Ser727 but not at Tyr705. CONCLUSION: STAT3 phosphorylation at Ser 727 and the interaction with PKCε contribute to hyperalgesia via the IL-6-mediated signaling pathway, thus regulating neuron-glia crosstalk during inflammatory pain.