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1.
J Biol Chem ; 299(1): 102748, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436564

RESUMO

Crustaceans have an open vascular system in which hemocytes freely circulate in hemolymph. Hemocytes are rich in hemocyanin, a specific oxygen-transport protein in crustaceans; therefore, understanding the response of hemocytes to hypoxia is crucial. Although hemocytes take up glucose during hypoxia, the molecular mechanism of glucose uptake in crustaceans remains unclear. Herein, we identified two highly conserved glucose transporters (GLUT1 and GLUT2) in Macrobrachium nipponense (oriental river prawn) and analyzed their tissue-specific expression patterns. Our immunofluorescence assays showed that GLUT1 and GLUT2 are located on the cell membrane, with a strong GLUT1 signal in primary hemocytes under hypoxia. We found that during acute hypoxia, hypoxia-inducible factor-1α-related metabolic alterations result in decreased mitochondrial cytochrome c oxidase activity, implying a classic glycolytic mechanism. As a proof of concept, we replicated these findings in insect S2 cells. Acute hypoxia significantly induced hypoxia-inducible factor-1α, GLUT1, and pyruvate dehydrogenase kinase isozyme 1 expression in primary hemocytes, and hypoxia-induced increases in glucose uptake and lactate secretion were observed. GLUT1 knockdown induced intracellular reactive oxygen species generation and apoptosis in vitro and in vivo, resulting in increased prawn mortality and more apoptotic cells in their brains, implying a vital function of GLUT1 in hypoxia adaptation. Taken together, our results suggest a close relationship between hypoxia-mediated glycolysis and GLUT1 in hemocytes. These results demonstrated that in crustaceans, adaptation to hypoxia involves glucose metabolic plasticity.


Assuntos
Palaemonidae , Animais , Palaemonidae/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Hemócitos/metabolismo , Regulação da Expressão Gênica , Hipóxia/metabolismo , Glucose/metabolismo
2.
J Cell Physiol ; 239(5): e31250, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38477420

RESUMO

Parkinson's disease (PD) is the most prevalent neurodegenerative disorder. Neuroinflammation mediated by activated microglia and apoptosis of dopaminergic (DA) neurons in the midbrain are its primary pathological manifestations. Leucine-rich repeat protein kinase 2 (LRRK2) kinase has been observed to increase expression during neuroinflammation, however, the effect of LRRK2 on microglia activation remains poorly understood. In this study, we have established lipopolysaccharide (LPS) treated BV2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models for both in vivo and in vitro investigation. Our data in vivo reveal that LRRK2 can promote microglia activation by regulating ferroptosis and activating nuclear factor-κB. Inhibition of LRRK2 expression effectively suppressed the LPS-induced pro-inflammatory cytokines and facilitated the secretion of neuroprotective factors. Importantly, by co-overexpressing LRRK2 and glutathione peroxidase 4 (GPX4), we identified the system Xc-GSH-GPX4 pathway as a crucial component in LRRK2-mediated microglial ferroptosis and inflammatory responses. Using a microglial culture supernatant (MCS) transfer model, we found that inhibiting LRRK2 or downregulating ferroptosis in BV2 cells prevented SH-SY5Y cell apoptosis. Additionally, we observed abundant expression of LRRK2 and P-P65 in the midbrain, which was elevated in the MPTP-induced PD model, along with microglia activation. LRRK2 and P-P65 expression inhibition with PF-06447475 attenuated microglia activation in the nigrostriatal dense part of MPTP-treated mice. Based on our findings, it is evident that LRRK2 plays a critical role in promoting the neuroinflammatory response during the pathogenesis of PD by regulating the system Xc-GSH-GPX4 pathway. Taken together, our data highlights the potential research and therapeutic value of targeting LRRK2 to regulate neuroinflammatory response in PD through ferroptosis.


Assuntos
Ferroptose , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Microglia , Doenças Neuroinflamatórias , Doença de Parkinson , Animais , Humanos , Masculino , Camundongos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Ferroptose/efeitos dos fármacos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , NF-kappa B/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Transdução de Sinais , Pirimidinas/farmacologia , Pirróis/farmacologia
3.
Biochem Biophys Res Commun ; 722: 150156, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38797155

RESUMO

Osteosarcoma, considered as the primary cause of malignant bone tumors in children, necessitates novel therapeutic strategies to enhance overall survival rates. KAT7, a histone acetyltransferase, exerts pivotal functions in gene transcription and immune modulation. In light of this, our study identified a significant upregulation of KAT7 in the mRNA and protein levels in human osteosarcoma, boosting cell proliferation in vivo and in vitro. In addition, KAT7-mediated H3K14ac activation induced MMP14 transcription, leading to increased expression and facilitation of osteosarcoma cell metastasis. Subsequent bioinformatics analyses highlighted a correlation between KAT7 and adaptive immune responses, indicating CCL3 as a downstream target of KAT7. Mechanistically, STAT1 was found to transcriptionally upregulate CCL3 expression. Furthermore, overexpression of KAT7 suppressed CCL3 secretions, whereas knockdown of KAT7 enhanced its release. Overall, these findings underscore the oncogenic role of KAT7 in regulating immune responses for osteosarcoma treatment.


Assuntos
Neoplasias Ósseas , Quimiocina CCL3 , Regulação Neoplásica da Expressão Gênica , Histona Acetiltransferases , Osteossarcoma , Fator de Transcrição STAT1 , Transdução de Sinais , Animais , Humanos , Camundongos , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Quimiocina CCL3/metabolismo , Quimiocina CCL3/genética , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Camundongos Nus , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética
4.
Plant Biotechnol J ; 22(6): 1468-1490, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38169146

RESUMO

Variation in anthocyanin biosynthesis in pear fruit provides genetic germplasm resources for breeding, while dwarfing is an important agronomic trait, which is beneficial to reduce the management costs and allow for the implementation of high-density cultivation. Here, we combined bulked segregant analysis (BSA), quantitative trait loci (QTL), and structural variation (SV) analysis to identify a 14-bp deletion which caused a frame shift mutation and resulted in the premature translation termination of a B-box (BBX) family of zinc transcription factor, PyBBX24, and its allelic variation termed PyBBX24ΔN14. PyBBX24ΔN14 overexpression promotes anthocyanin biosynthesis in pear, strawberry, Arabidopsis, tobacco, and tomato, while that of PyBBX24 did not. PyBBX24ΔN14 directly activates the transcription of PyUFGT and PyMYB10 through interaction with PyHY5. Moreover, stable overexpression of PyBBX24ΔN14 exhibits a dwarfing phenotype in Arabidopsis, tobacco, and tomato plants. PyBBX24ΔN14 can activate the expression of PyGA2ox8 via directly binding to its promoter, thereby deactivating bioactive GAs and reducing the plant height. However, the nuclear localization signal (NLS) and Valine-Proline (VP) motifs in the C-terminus of PyBBX24 reverse these effects. Interestingly, mutations leading to premature termination of PyBBX24 were also identified in red sports of un-related European pear varieties. We conclude that mutations in PyBBX24 gene link both an increase in pigmentation and a decrease in plant height.


Assuntos
Proteínas de Plantas , Pyrus , Pyrus/genética , Pyrus/metabolismo , Pyrus/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Alelos , Antocianinas/metabolismo , Pigmentação/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Locos de Características Quantitativas/genética , Plantas Geneticamente Modificadas/genética , Frutas/genética , Frutas/metabolismo , Frutas/crescimento & desenvolvimento , Nicotiana/genética , Nicotiana/metabolismo , Fenótipo
5.
Plant Physiol ; 192(4): 2604-2627, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37163660

RESUMO

Fruit crops cultivated in almost all countries and regions around the world serve as important agricultural commodities of significant economic value because they contribute to overall food security by providing a diverse food and nutrient supply to sustain human life and human health. Recent advances in high-throughput sequencing technologies offer unprecedented opportunities for pursuing genomic and genetic studies of fruit crops. Here, we will review major advances in fruit crop genome sequencing efforts undertaken over the past 15 years that have contributed to significant accumulation of publicly available genomic resources. We will highlight the expanding pool of genomic data that offer unprecedented opportunities to better unravel the genetic origin and domestication of fruit trees, as well as in deciphering the genetics of important horticultural traits of these fruit trees. Furthermore, we will explore how utilization of these genetic features of fruit trees along with new genomic-assisted tools, including genomic selection and gene editing, are informing and guiding plant geneticists and breeders in moving forward in their fruit crop breeding efforts. Finally, we will outline future prospects and unresolved questions that remain in both genomic research and genetic improvement of fruit crops.


Assuntos
Domesticação , Frutas , Humanos , Frutas/genética , Melhoramento Vegetal , Genômica , Produtos Agrícolas/genética , Genoma de Planta/genética
6.
Plant Physiol ; 192(3): 1997-2014, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37011145

RESUMO

Lignified stone cell content is a key factor used to evaluate fruit quality, influencing the economic value of pear (Pyrus pyrifolia) fruits. However, our understanding of the regulatory networks of stone cell formation is limited due to the complex secondary metabolic pathway. In this study, we used a combination of co-expression network analysis, gene expression profiles, and transcriptome analysis in different pear cultivars with varied stone cell content to identify a hub MYB gene, PbrMYB24. The relative expression of PbrMYB24 in fruit flesh was significantly correlated with the contents of stone cells, lignin, and cellulose. We then verified the function of PbrMYB24 in regulating lignin and cellulose formation via genetic transformation in homologous and heterologous systems. We constructed a high-efficiency verification system for lignin and cellulose biosynthesis genes in pear callus. PbrMYB24 transcriptionally activated multiple target genes involved in stone cell formation. On the one hand, PbrMYB24 activated the transcription of lignin and cellulose biosynthesis genes by binding to different cis-elements [AC-I (ACCTACC) element, AC-II (ACCAACC) element and MYB-binding sites (MBS)]. On the other hand, PbrMYB24 bound directly to the promoters of PbrMYB169 and NAC STONE CELL PROMOTING FACTOR (PbrNSC), activating the gene expression. Moreover, both PbrMYB169 and PbrNSC activated the promoter of PbrMYB24, enhancing gene expression. This study improves our understanding of lignin and cellulose synthesis regulation in pear fruits through identifying a regulator and establishing a regulatory network. This knowledge will be useful for reducing the stone cell content in pears via molecular breeding.


Assuntos
Frutas , Pyrus , Frutas/genética , Frutas/metabolismo , Pyrus/genética , Pyrus/metabolismo , Lignina/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas
7.
Kidney Blood Press Res ; 49(1): 60-68, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38167222

RESUMO

INTRODUCTION: It has been reported that rapamycin inhibited inflammation in renal interstitial diseases. We therefore hypothesized that rapamycin could attenuate inflammation in polycystic kidney disease (PKD). METHODS: Han:SPRD rats were treated with rapamycin by daily gavage from 4 weeks to 12 weeks of age at the dosage of 0.5 mg/kg/day (low dose) or 1 mg/kg/day (high dose). WT9-12 human PKD cells were treated with various concentrations of rapamycin. RESULTS: Two-kidney/total body weight ratio and cystic index in Cy/+ kidneys were significantly reduced with the treatment of low-dose rapamycin and further reduced by the treatment with high-dose rapamycin. However, the renal function of Cy/+ rats was equally improved by the treatment with either low-dose or high-dose rapamycin. The renal cell proliferation was significantly decreased in Cy/+ kidneys with the treatment of low-dose rapamycin and was further decreased with the treatment of high-dose rapamycin as examined by Ki67 staining. The phosphorylation of S6K in cystic kidneys was decreased by low-dose rapamycin and further decreased by high-dose rapamycin. Both low-dose and high-dose rapamycin treatment decreased macrophage infiltration and the expression of complement factor B (CFB), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) to a similar level. The expression of CFB, MCP-1, and TNF-α and phosphorylation of S6K were inhibited in WT9-12 cells treated with 10 nm rapamycin at 24 h and 48 h, respectively. Moreover, the phosphorylation of Akt was not increased by 1 nm and 10 nm of rapamycin and enhanced by 1 µm rapamycin treatment. Interestingly, WT9-12 cell proliferation could be inhibited by 1 µm rapamycin. CONCLUSION: Low dose of rapamycin could inhibit inflammation and protect renal function in PKD. Inflammation is more sensitive than cell proliferation in response to rapamycin treatment in PKD.


Assuntos
Doenças Renais Policísticas , Rim Policístico Autossômico Dominante , Ratos , Humanos , Animais , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/metabolismo , Fator de Necrose Tumoral alfa , Doenças Renais Policísticas/patologia , Rim/patologia , Inflamação/patologia , Proliferação de Células , Modelos Animais de Doenças
8.
Entropy (Basel) ; 26(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38539734

RESUMO

Aiming at the difficult problem of extracting fault characteristics and the low accuracy of fault diagnosis throughout the full life cycle of rolling bearings, a fault diagnosis method for rolling bearings based on grey relation degree is proposed in this paper. Firstly, the subtraction-average-based optimizer is used to optimize the parameters of the variational mode decomposition algorithm. Secondly, the vibration signals of bearings are decomposed by using the optimized results, and the feature vector of the intrinsic mode function component corresponding to the minimum envelope entropy is extracted. Finally, the grey proximity and similarity relation degree based on standard distance entropy are weighted to calculate the grey comprehensive relation degree between the feature vector of vibration signals and each standard state. By comparing the results, the diagnosis of different fault states and degrees of rolling bearings is realized. The XJTU-SY dataset was used for experimentation, and the results show that the proposed method achieves a diagnostic accuracy of 95.24% and has better diagnosis performance compared to various algorithms. It provides a reference for the fault diagnosis of rolling bearings throughout the full life cycle.

9.
Zhongguo Zhong Yao Za Zhi ; 49(2): 315-324, 2024 Jan.
Artigo em Zh | MEDLINE | ID: mdl-38403307

RESUMO

Drying is an indispensable processing step for Chinese medicinal materials after harvesting. It often leads to significant changes in the active components of these materials, thus impacting their medicinal values. Understanding the mechanisms behind the changes during the drying process is of great importance for regulating the transformation of key active components. Therefore, this paper reviews the available studies and comprehensively expounds the mechanisms underlying the changes in active components during the drying process. The aim is to offer insights for the development of regulatory strategies and the improvement of drying techniques for Chinese medicinal materials.


Assuntos
Medicamentos de Ervas Chinesas , Dessecação
10.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1699-1704, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621954

RESUMO

The quality of traditional Chinese medicine preparations is directly related to the safety of patients. Among the various factors, the process and corresponding critical equipment are critical factors influencing the quality of the preparations. To improve the quality of traditional Chinese medicine preparations, this article summarizes and analyzes the problems in the process links and corresponding critical equipment in the manufacturing process of traditional Chinese medicine preparations. Furthermore, a critical quality attribute evaluation system is established based on safety and effectiveness combined with the drug properties, preparation process, and preparation characteristics, providing a basis for the process and equipment improvements aimed at quality enhancement.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Controle de Qualidade , Comércio
11.
Angew Chem Int Ed Engl ; 63(2): e202313796, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38015565

RESUMO

Modulation of the microenvironment on the electrode surface is one of the effective means to improve the efficiency of electrocatalytic carbon dioxide reduction (eCO2 RR). To achieve high conversion rates, the phase boundary at the electrode surface should be finely controlled to overcome the limitation of CO2 solubility in the aqueous electrolyte. Herein, we developed a simple and efficient method to structure electrocatalyst with a superhydrophobic surface microenvironment by one-step co-electrodeposition of Cu and polytetrafluoroethylene (PTFE) on carbon paper. The super-hydrophobic Cu-based electrode displayed a high ethylene (C2 H4 ) selectivity with a Faraday efficiency (FE) of 67.3 % at -1.25 V vs. reversible hydrogen electrode (RHE) in an H-type cell, which is 2.5 times higher than a regular Cu electrode without PTFE. By using PTFE as a surface modifier, the activity of eCO2 RR is enhanced and water (proton) adsorption is inhibited. This strategy has the potential to be applied to other gas-conversion electrocatalysts.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 378-384, 2024 Apr 15.
Artigo em Zh | MEDLINE | ID: mdl-38660902

RESUMO

OBJECTIVES: To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI. METHODS: A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves. RESULTS: Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group (P<0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup (P<0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores (P<0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment (P<0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively (P<0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively (P<0.05). CONCLUSIONS: Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.


Assuntos
Proteína Beclina-1 , Lesões Encefálicas Traumáticas , Subunidade alfa do Fator 1 Induzível por Hipóxia , Proteínas de Membrana , Humanos , Masculino , Feminino , Lesões Encefálicas Traumáticas/sangue , Criança , Proteínas de Membrana/sangue , Pré-Escolar , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Proteína Beclina-1/sangue , Prognóstico , Proteínas Proto-Oncogênicas/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Estudos Prospectivos , Lactente , Adolescente
13.
BMC Plant Biol ; 23(1): 430, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37710163

RESUMO

BACKGROUND: Pears are among the most important temperate fruit trees in the world, with significant research efforts increasing over the last years. However, available omics data for pear cannot be easily and quickly retrieved to enable further studies using these biological data. DESCRIPTION: Here, we present a publicly accessible multi-omics pear resource platform, the Pear Genomics Database (PGDB). We collected and collated data on genomic sequences, genome structure, functional annotation, transcription factor predictions, comparative genomics, and transcriptomics. We provide user-friendly functional modules to facilitate querying, browsing and usage of these data. The platform also includes basic and useful tools, including JBrowse, BLAST, phylogenetic tree building, and additional resources providing the possibility for bulk data download and quick usage guide services. CONCLUSIONS: The Pear Genomics Database (PGDB, http://pyrusgdb.sdau.edu.cn ) is an online data analysis and query resource that integrates comprehensive multi-omics data for pear. This database is equipped with user-friendly interactive functional modules and data visualization tools, and constitutes a convenient platform for integrated research on pear.


Assuntos
Pyrus , Pyrus/genética , Multiômica , Filogenia , Bases de Dados Factuais , Genômica
14.
Plant Biotechnol J ; 21(7): 1408-1425, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37031416

RESUMO

Stone cells are often present in pear fruit, and they can seriously affect the fruit quality when present in large numbers. The plant growth regulator NAA, a synthetic auxin, is known to play an active role in fruit development regulation. However, the genetic mechanisms of NAA regulation of stone cell formation are still unclear. Here, we demonstrated that exogenous application of 200 µM NAA reduced stone cell content and also significantly decreased the expression level of PbrNSC encoding a transcriptional regulator. PbrNSC was shown to bind to an auxin response factor, PbrARF13. Overexpression of PbrARF13 decreased stone cell content in pear fruit and secondary cell wall (SCW) thickness in transgenic Arabidopsis plants. In contrast, knocking down PbrARF13 expression using virus-induced gene silencing had the opposite effect. PbrARF13 was subsequently shown to inhibit PbrNSC expression by directly binding to its promoter, and further to reduce stone cell content. Furthermore, PbrNSC was identified as a positive regulator of PbrMYB132 through analyses of co-expression network of stone cell formation-related genes. PbrMYB132 activated the expression of gene encoding cellulose synthase (PbrCESA4b/7a/8a) and lignin laccase (PbrLAC5) binding to their promotors. As expected, overexpression or knockdown of PbrMYB132 increased or decreased stone cell content in pear fruit and SCW thickness in Arabidopsis transgenic plants. In conclusion, our study shows that the 'PbrARF13-PbrNSC-PbrMYB132' regulatory cascade mediates the biosynthesis of lignin and cellulose in stone cells of pear fruit in response to auxin signals and also provides new insights into plant SCW formation.


Assuntos
Arabidopsis , Pyrus , Frutas/metabolismo , Lignina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas
15.
Am J Physiol Regul Integr Comp Physiol ; 324(1): R128-R142, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468826

RESUMO

The hypoxia-inducible factor 1 (HIF-1) cascade is an ancient and strongly evolutionarily conserved signaling pathway that is involved in the hypoxic responses of most metazoans. Despite immense advances in the understanding of the HIF-1-mediated regulation of hypoxic responses in mammals, the contribution of the hif-1 cascade in the hypoxic adaptation of nonmodel invertebrates remains unclear. In this study, we used the oriental river prawn Macrobrachium nipponense for investigating the roles of hif-1-regulated mitophagy in crustacean testes under hypoxic conditions. We identified that the Bcl-2/adenovirus E1B 19-kDa interacting protein (bnip3) functions as a regulator of mitophagy in M. nipponense and demonstrated that hif-1α activates bnip3 by binding to the bnip3 promoter. Hif-1α knockdown suppressed the expression of multiple mitophagy-related genes, and prawns with hif-1α knockdown exhibited higher mortality under hypoxic conditions. We observed that the levels of BNIP3 were induced under hypoxic conditions and detected that bnip3 knockdown inhibited the mitochondrial translocation of dynamin-related protein 1 (drp1), which is associated with mitochondrial fission. Notably, bnip3 knockdown inhibited hypoxia-induced mitophagy and aggravated the deleterious effects of hypoxia-induced reactive oxygen species (ROS) production and apoptosis. The experimental studies demonstrated that hypoxia induced mitochondrial fission in M. nipponense via drp1. Altogether, the study elucidated the mechanism underlying hif-1/bnip3-mediated mitochondrial fission and mitophagy and demonstrated that this pathway protects crustaceans against ROS production and apoptosis induced by acute hypoxia.


Assuntos
Mitofagia , Testículo , Masculino , Animais , Mitofagia/genética , Espécies Reativas de Oxigênio/metabolismo , Testículo/metabolismo , Dinâmica Mitocondrial , Hipóxia/metabolismo , Apoptose , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mamíferos/metabolismo
16.
Phys Rev Lett ; 131(25): 256002, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38181352

RESUMO

The Fe_{4}Se_{5} with a sqrt[5]×sqrt[5] Fe vacancy order is suggested to be a Mott insulator and the parent state of bulk FeSe superconductor. The iron vacancy ordered state has been considered as a Mott insulator and the parent compound of bulk FeSe-based superconductors. However, for the superconducting FeSe/SrTiO_{3} monolayer (FeSe/STO) with an interface-enhanced high transition temperature (T_{c}), the electronic evolution from its Fe vacancy ordered parent phase to the superconducting state, has not been explored due to the challenge to realize an Fe vacancy order in the FeSe/STO monolayer, even though important to the understanding of superconductivity mechanism. In this study, we developed a new method to generate Fe vacancies within the FeSe/STO monolayer in a tunable fashion, with the assistance of atomic hydrogen. As a consequence, an insulating sqrt[5]×sqrt[5] Fe vacancy ordered monolayer is realized as the parent state. By using scanning tunneling microscopy and scanning tunneling spectroscopy, the spectral evolution from superconductivity to insulator is fully characterized. Surprisingly, a prominent spectral weight transfer occurs, thus implying a strong electron correlation effect. Moreover, the Fe vacancy induced insulating gap exhibits no Mott gap-like features. This work provides new insights in understanding the high-T_{c} superconductivity in FeSe/STO monolayer.

17.
Int Arch Allergy Immunol ; 184(4): 376-390, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36603560

RESUMO

INTRODUCTION: As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. METHODS: The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components. RESULTS: The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. CONCLUSIONS: In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.


Assuntos
Rinite Alérgica , Camundongos , Animais , Regulação para Baixo , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/metabolismo , Mucosa Nasal/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Ovalbumina
18.
Int Arch Allergy Immunol ; 184(6): 529-538, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37231897

RESUMO

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.


Assuntos
Transtornos do Olfato , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/terapia , Humanos , Cavidade Nasal , Prognóstico , Inflamação
19.
FASEB J ; 36(8): e22477, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35881071

RESUMO

Diabetes may prevent kidney repair and sensitize the kidney to fibrosis or scar formation. To test this possibility, we examined renal fibrosis induced by unilateral ureteral obstruction (UUO) in diabetic mouse models. Indeed, UUO induced significantly more renal fibrosis in both Akita and STZ-induced diabetic mice than in nondiabetic mice. The diabetic mice also had more apoptosis and interstitial macrophage infiltration during UUO. In vitro, hypoxia induced higher expression of the fibrosis marker protein fibronectin in high glucose-conditioned renal tubular cells than in normal glucose cells. Mechanistically, hypoxia induced significantly more hypoxia-inducible factor-1 α (HIF-1 α) in high glucose cells than in normal glucose cells. Inhibition of HIF-1 attenuated the expression of fibronectin induced by hypoxia in high-glucose cells. Consistently, UUO induced significantly higher HIF-1α expression along with fibrosis in diabetic mice kidneys than in nondiabetic kidneys. The increased expression of fibrosis induced by UUO in diabetic mice was diminished in proximal tubule-HIF-1α-knockout mice. Together, these results indicate that diabetes sensitizes kidney tissues and cells to fibrogenesis probably by enhancing HIF-1 activation.


Assuntos
Diabetes Mellitus Experimental , Nefropatias , Obstrução Ureteral , Animais , Diabetes Mellitus Experimental/metabolismo , Fibronectinas/metabolismo , Fibrose , Glucose/metabolismo , Hipóxia/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Nefropatias/patologia , Camundongos , Obstrução Ureteral/metabolismo
20.
Acta Pharmacol Sin ; 44(4): 710-725, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36207402

RESUMO

C1q/tumor necrosis factor (TNF) related proteins (CTRPs) is a newly discovered adipokine family with conservative structure and ubiquitous distribution and is secreted by adipose tissues. Recently, CTRPs have attracted increasing attention due to the its wide-ranging effects upon inflammation and metabolism. To-date, 15 members of CTRPs (CTRP1-15) with the characteristic C1q domain have been characterized. Earlier in-depth phenotypic analyses of mouse models of CTRPs deficiency have also unveiled ample function of CTRPs in inflammation and metabolism. This review focuses on the rise of CTRPs, with a special emphasis on the latest discoveries with regards to the effects of the CTRP family on inflammation and metabolism as well as related diseases. We first introduced the structure of characteristic domain and polymerization of CTRPs to reveal its pleiotropic biological functions. Next, intimate association of CTRP family with inflammation and metabolism, as well as the involvement of CTRPs as nodes in complex molecular networks, were elaborated. With expanding membership of CTRP family, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.


Assuntos
Adipocinas , Inflamação , Animais , Camundongos , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Complemento C1q , Inflamação/metabolismo
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