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Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome.
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Células-Tronco Embrionárias/virologia , Retrovirus Endógenos/genética , Provírus/genética , Animais , Fator 1 de Modelagem da Cromatina/genética , Fator 1 de Modelagem da Cromatina/metabolismo , Células-Tronco de Carcinoma Embrionário/virologia , Epigênese Genética , Camundongos , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismoRESUMO
Body mass index (BMI) has been found to have an impact on neurodegenerative diseases such as Parkinson's disease (PD). Several studies suggested that patients with PD have a lower BMI compared with controls. However, some studies indicated the differences between patients and controls as statistically insignificant. We performed this meta-analysis to clarify the relationship between BMI and PD based on the studies published from 1975 to April 2023 in the PubMed, Embase, and Cochrane Library databases. In total, 18 case-control studies met the inclusion criteria for meta-analysis. We found a statistically significant difference in mean BMI between patients with PD and healthy controls {standardized mean difference (SMD) [95% confidence interval (CI)] = -0.36 (-0.43, -0.29), P < 0.05}. Regarding sex, seven studies were included in the meta-analysis for female/male patients with PD. The mean BMI was significantly different between males with PD and healthy males [SMD (95% CI) = -0.34 (-0.47, -0.22), P < 0.05]. Moreover, the mean BMI of females with PD was significantly different from that of corresponding healthy females [SMD (95% CI) = -0.44 (-0.57, -0.30), P < 0.05]. The meta-analysis demonstrates a significantly lower BMI in patients with PD, but no gender differences, when compared with their respective healthy individuals.NEW & NOTEWORTHY The meta-analysis demonstrates a significantly lower body mass index in patients with PD, but no gender differences, when compared with their respective healthy individuals.
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Índice de Massa Corporal , Doença de Parkinson , Doença de Parkinson/fisiopatologia , Humanos , Masculino , Feminino , Fatores SexuaisRESUMO
Alpha-synuclein (α-syn) is a major component of Lewy bodies, which is a biomarker of Parkinson's disease (PD). It accumulates in substantia nigra pars compacta (SNpc) to form insoluble aggregates and cause neurotoxicity, which is often accompanied by iron deposition. We compared the iron reductase activity between monomeric α-syn (M-α-syn) and oligomeric α-syn (O-α-syn) and investigated the effect of α-syn on iron metabolism of BV2 microglia cells as well. α-syn had ferric reductase activity, and O-α-syn had stronger enzyme activity than M-α-syn. M-α-syn upregulated iron uptake protein, divalent metal transporter1 (DMT1) expression, and iron influx but did not regulate iron release protein ferroportin1 (FPN1) expression and iron efflux. O-α-syn elevated the expression of both DMT1 and FPN1 and thus increased the iron influx and efflux in BV2 microglial cells, but the expressions of iron regulatory protein1 (IRP1) and hypoxia-inducible factor 2α (HIF-2α) had no significant change. Moreover, both M-α-syn and O-α-syn could increase the mRNA expressions of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in BV2 microglia cells. Both types of α-syn can activate microglia, which leads to increased expressions of proinflammatory factors. α-syn can affect DMT1 and FPN1 expressions in BV2 microglia cells, which might be through its ferric reductase activity.NEW & NOTEWORTHY The effects of monomeric α-syn (M-α-syn) and oligomeric α-syn (O-α-syn) on the iron metabolism of BV2 microglia cells were detected by exogenous α-syn treatment. This study provides a strong experimental basis for α-syn involvement in iron metabolism in microglia.
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Proteínas de Transporte de Cátions , FMN Redutase , Ferro , Microglia , alfa-Sinucleína , Microglia/metabolismo , Animais , Camundongos , Proteínas de Transporte de Cátions/metabolismo , alfa-Sinucleína/metabolismo , FMN Redutase/metabolismo , Ferro/metabolismo , Linhagem Celular , Proteína 1 Reguladora do Ferro/metabolismo , Interleucina-1beta/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
BACKGROUND: To establish a strategy for stem cell-related tissue regeneration therapy, human gingival mesenchymal stem cells (hGMSCs) were loaded with three-dimensional (3D) bioengineered Matrigel matrix scaffolds in high-cell density microtissues to promote local tissue restoration. METHODS: The biological performance and stemness of hGMSCs under 3D culture conditions were investigated by viability and multidirectional differentiation analyses. A SpragueâDawley (SD) rat full-thickness buccal mucosa wound model was established, and hGMSCs/Matrigel were injected into the submucosa of the wound. Autologous stem cell proliferation and wound repair in local tissue were assessed by histomorphometry and immunohistochemical staining. RESULTS: Three-dimensional suspension culture can provide a more natural environment for extensions and contacts between hGMSCs, and the viability and adipogenic differentiation capacity of hGMSCs were significantly enhanced. An animal study showed that hGMSCs/Matrigel significantly accelerated soft tissue repair by promoting autologous stem cell proliferation and enhancing the generation of collagen fibers in local tissue. CONCLUSION: Three-dimensional cell culture with hydrogel scaffolds, such as Matrigel, can effectively improve the biological function and maintain the stemness of stem cells. The therapeutic efficacy of hGMSCs/Matrigel was confirmed, as these cells could effectively stimulate soft tissue repair to promote the healing process by activating the host microenvironment and autologous stem cells.
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Colágeno , Combinação de Medicamentos , Laminina , Células-Tronco Mesenquimais , Proteoglicanas , Ratos Sprague-Dawley , Alicerces Teciduais , Cicatrização , Animais , Laminina/química , Proteoglicanas/química , Colágeno/química , Humanos , Ratos , Células-Tronco Mesenquimais/citologia , Alicerces Teciduais/química , Diferenciação Celular , Proliferação de Células , Gengiva/citologia , Técnicas de Cultura de Células em Três Dimensões/métodos , Células Cultivadas , Engenharia Tecidual/métodos , Masculino , Mucosa Bucal/citologiaRESUMO
BACKGROUND: Cerebral malaria (CM) is the most lethal complication of malaria, and survivors usually endure neurological sequelae. Notably, the cytotoxic effect of infiltrating Plasmodium-activated CD8+ T cells on cerebral microvasculature endothelial cells is a prominent feature of the experimental CM (ECM) model with blood-brain barrier disruption. However, the damage effect of CD8+ T cells infiltrating the brain parenchyma on neurons remains unclear. Based on the immunosuppressive effect of the PD-1/PD-L1 pathway on T cells, our previous study demonstrated that the systemic upregulation of PD-L1 to inhibit CD8+ T cell function could effectively alleviate the symptoms of ECM mice. However, it has not been reported whether neurons can suppress the pathogenic effect of CD8+ T cells through the PD-1/PD-L1 negative immunomodulatory pathway. As the important inflammatory factor of CM, interferons can induce the expression of PD-L1 via different molecular mechanisms according to the neuro-immune microenvironment. Therefore, this study aimed to investigate the direct interaction between CD8+ T cells and neurons, as well as the mechanism of neurons to alleviate the pathogenic effect of CD8+ T cells through up-regulating PD-L1 induced by IFNs. METHODS: Using the ECM model of C57BL/6J mice infected with Plasmodium berghei ANKA (PbA), morphological observations were conducted in vivo by electron microscope and IF staining. The interaction between the ECM CD8+ T cells (immune magnetic bead sorting from spleen of ECM mice) and primary cultured cortical neurons in vitro was observed by IF staining and time-lapse photography. RNA-seq was performed to analyze the signaling pathway of PD-L1 upregulation in neurons induced by IFNß or IFNγ, and verified through q-PCR, WB, IF staining, and flow cytometry both in vitro and in vivo using IFNAR or IFNGR gene knockout mice. The protective effect of adenovirus-mediated PD-L1 IgGFc fusion protein expression was verified in ECM mice with brain stereotaxic injection in vivo and in primary cultured neurons via viral infection in vitro. RESULTS: In vivo, ECM mice showed infiltration of activated CD8+ T cells and neuronal injury in the brain parenchyma. In vitro, ECM CD8+ T cells were in direct contact with neurons and induced axonal damage, as an active behavior. The PD-L1 protein level was elevated in neurons of ECM mice and in primary cultured neurons induced by IFNß, IFNγ, or ECM CD8+ T cells in vitro. Furthermore, the IFNß or IFNγ induced neuronal expression of PD-L1 was mediated by increasing STAT1/IRF1 pathway via IFN receptors. The increase of PD-L1 expression in neurons during PbA infection was weakened after deleting the IFNAR or IFNGR. Increased PD-L1 expression by adenovirus partially protected neurons from CD8+ T cell-mediated damage both in vitro and in vivo. CONCLUSION: Our study demonstrates that both type I and type II IFNs can induce neurons to upregulate PD-L1 via the STAT1/IRF1 pathway mediated by IFN receptors to protect against activated CD8+ T cell-mediated damage, providing a targeted pathway to alleviate neuroinflammation during ECM.
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Antígeno B7-H1 , Linfócitos T CD8-Positivos , Malária Cerebral , Camundongos Endogâmicos C57BL , Neurônios , Fator de Transcrição STAT1 , Regulação para Cima , Animais , Camundongos , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Fator Regulador 1 de Interferon/metabolismo , Interferon gama/metabolismo , Malária Cerebral/imunologia , Malária Cerebral/metabolismo , Malária Cerebral/patologia , Camundongos Knockout , Neurônios/metabolismo , Plasmodium berghei , Transdução de Sinais/fisiologia , Fator de Transcrição STAT1/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Soybean is a short-day plant that typically flowers earlier when exposed to short-day conditions. However, the identification of genes associated with earlier flowering time but without a yield penalty is rare. In this study, we conducted genome-wide association studies (GWAS) using two re-sequencing datasets that included 113 wild soybeans (G. soja) and 1192 cultivated soybeans (G. max), respectively, and simultaneously identified a candidate flowering gene, qFT13-3, which encodes a protein homologous to the pseudo-response regulator (PRR) transcription factor. We identified four major haplotypes of qFT13-3 in the natural population, with haplotype H4 (qFT13-3H4) being lost during domestication, while qFT13-3H1 underwent natural and artificial selection, increasing in proportion from 4.5% in G. soja to 43.8% in landrace and to 81.9% in improve cultivars. Notably, most cultivars harbouring qFT13-3H1 were located in high-latitude regions. Knockout of qFT13-3 accelerated flowering and maturity time under long-day conditions, indicating that qFT13-3 functions as a flowering inhibitor. Our results also showed that qFT13-3 directly downregulates the expression of GmELF3b-2 which is a component of the circadian clock evening complex. Field trials revealed that the qft13-3 mutants shorten the maturity period by 11 days without a concomitant penalty on yield. Collectively, qFT13-3 can be utilized for the breeding of high-yield cultivars with a short maturity time suitable for high latitudes.
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Estudo de Associação Genômica Ampla , Glycine max , Glycine max/genética , Melhoramento Vegetal , Haplótipos/genética , Fotoperíodo , Flores/genética , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genéticaRESUMO
As space exploration programs progress, manned space missions will become more frequent and farther away from Earth, putting a greater emphasis on astronaut health. Through the collaborative efforts of researchers from various countries, the effect of the space environment factors on living systems is gradually being uncovered. Although a large number of interconnected research findings have been produced, their connection seems to be confused, and many unknown effects are left to be discovered. Simultaneously, several valuable data resources have emerged, accumulating data measuring biological effects in space that can be used to further investigate the unknown biological adaptations. In this review, the previous findings and their correlations are sorted out to facilitate the understanding of biological adaptations to space and the design of countermeasures. The biological effect measurement methods/data types are also organized to provide references for experimental design and data analysis. To aid deeper exploration of the data resources, we summarized common characteristics of the data generated from longitudinal experiments, outlined challenges or caveats in data analysis and provided corresponding solutions by recommending bioinformatics strategies and available models/tools.
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Disciplinas das Ciências Biológicas , Voo Espacial , Biologia ComputacionalRESUMO
The common wheat line 4N0461 showed adult-plant resistance to leaf rust. 4N0461 was crossed with susceptible cultivars Nongda4503 and Shi4185 to map the causal resistance gene(s). Segregation of leaf rust response in F2 populations from both crosses was 9 resistant:7 susceptible, indicative of two complementary dominant resistance genes. The genes were located on chromosome arms 3BS and 4BL and temporarily named LrN3B and LrN4B, respectively. Subpopulations from 4N0461 × Nongda4503 with LrN3B segregating as a single allele were used to fine-map LrN3B locus. LrN3B was delineated in a genetic interval of 0.07 cM, corresponding to 106 kb based on the Chinese Spring reference genome (IWGSC RefSeq v1.1). Four genes were annotated in this region, among which TraesCS3B02G014800 and TraesCS3B02G014900 differed between resistant and susceptible genotypes, and both were required for LrN3B resistance in virus-induced gene silencing experiments. Diagnostic markers developed for checking the polymorphism of each candidate gene, can be used for marker-assisted selection in wheat breeding programs.
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Basidiomycota , Mapeamento Cromossômico , Cromossomos de Plantas , Resistência à Doença , Genes de Plantas , Doenças das Plantas , Triticum , Triticum/genética , Triticum/microbiologia , Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Basidiomycota/patogenicidade , Basidiomycota/fisiologia , Cromossomos de Plantas/genética , Marcadores Genéticos , Genótipo , AlelosRESUMO
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of iron in the substantia nigra. While iron accumulation and inflammation are implicated in PD pathogenesis, their impact on oligodendrocytes, the brain's myelin-forming cells, remains elusive. This study investigated the influence of interleukin-1ß (IL-1ß), an elevated proinflammatory cytokine in PD, on iron-related proteins in MO3.13 oligodendrocytes. We found that IL-1ß treatment in undifferentiated MO3.13 oligodendrocytes increased iron regulatory protein 1 and transferrin receptor 1 (TfR1) expression while decreasing ferroportin 1 (FPN1) expression. Consequently, iron uptake was enhanced, and iron release was reduced, leading to intracellular iron accumulation. Conversely, IL-1ß treatment in differentiated MO3.13 oligodendrocytes exhibited the opposite effect, with decreased TfR1 expression, increased FPN1 expression, and reduced iron uptake. These findings suggest that IL-1ß-induced dysregulation of iron metabolism in oligodendrocytes may contribute to the pathological processes observed in PD. IL-1ß can increase the iron content in undifferentiated oligodendrocytes, thus facilitating the differentiation of undifferentiated MO3.13 oligodendrocytes. In differentiated oligodendrocytes, IL-1ß may facilitate iron release, providing a potential source of iron for neighboring dopaminergic neurons, thereby initiating a cascade of deleterious events. This study provides valuable insights into the intricate interplay between inflammation, abnormal iron accumulation, and oligodendrocyte dysfunction in PD. Targeting the IL-1ß-mediated alterations in iron metabolism may hold therapeutic potential for mitigating neurodegeneration and preserving dopaminergic function in PD.
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Proteína 1 Reguladora do Ferro , Doença de Parkinson , Humanos , Interleucina-1beta/metabolismo , Proteína 1 Reguladora do Ferro/metabolismo , Doença de Parkinson/metabolismo , Ferro/metabolismo , Inflamação/metabolismo , Oligodendroglia/metabolismoRESUMO
Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.
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Doenças Cardiovasculares , Pequeno RNA não Traduzido , RNA de Transferência , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Animais , RNA de Transferência/genética , RNA de Transferência/metabolismo , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/uso terapêutico , Pequeno RNA não Traduzido/metabolismoRESUMO
Alkylamine ligand-induced evolutions of ZnSe magic sized clusters (MSCs) toward divergent products have been discovered for the first time. With correspondingly assigned molecular structures, the same ZnSe MSC was found to undergo either single-atom growth or dissolution through the elaborate tailoring of alkylamine ligands.
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Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a destructive wheat disease pathogen. Thinopyrum elongatum is a valuable germplasm including diploid, tetraploid, and decaploid with plenty of biotic and abiotic resistance. In a previous study, we generated a stripe rust-resistant wheat-tetraploid Th. elongatum 1E/1D substitution line, K17-841-1. To further apply the wild germplasm for wheat breeding, we selected and obtained a new homozygous wheat-tetraploid Th. elongatum translocation line, T1BSâ 1EL, using genomic in situ hybridization, fluorescence in situ hybridization (FISH), oligo-FISH painting, and the wheat 55K single nucleotide polymorphism genotyping array. The T1BSâ 1EL is highly resistant to stripe rust at the seedling and adult stages. Pedigree and molecular marker analyses revealed that the resistance gene was located on the chromosome arm 1EL of tetraploid Th. elongatum, tentatively named Yr1EL. In addition, we developed and validated 32 simple sequence repeat markers and two kompetitive allele-specific PCR assays that were specific to the tetraploid Th. elongatum chromosome arm 1EL to facilitate marker-assisted selection for alien 1EL stripe rust resistance breeding. This will help us explore and locate the stripe rust resistance gene mapping on the 1E chromosome and deploy it in the wheat breeding program.
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Resistência à Doença , Doenças das Plantas , Poaceae , Puccinia , Tetraploidia , Translocação Genética , Triticum , Triticum/microbiologia , Triticum/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Resistência à Doença/genética , Poaceae/genética , Poaceae/microbiologia , Puccinia/fisiologia , Cromossomos de Plantas/genética , Basidiomycota/fisiologia , Melhoramento Vegetal , Hibridização in Situ Fluorescente , Polimorfismo de Nucleotídeo Único/genética , Genoma de Planta/genéticaRESUMO
PURPOSE: To investigate the balance between post-treatment effect and continued nature growth after maxillary protraction treatment in patients with skeletal class III malocclusion. METHODS: 31 patients aged 8.79 ± 1.65 years with skeletal Class III malocclusion had been treated with maxillary protraction and the treatment lasted an average of 1.16 years. The average observation duration after treatment in the maxillary protraction group was 2.05 ± 0.39 years. In the control groups, a sample of 22 patients (9.64 ± 2.53 years) with untreated skeletal class III malocclusion and 24 patients (9.28 ± 0.96 years) with skeletal class I malocclusion were matched to the treatment group according to age, sex and observation period. The mean observation interval of the control groups was 2.39 ± 1.29 years in the class III group and 1.97 ± 0.49 years in the class I group. RESULTS: The active orthopedic treatment effect showed a opposite trend to the natural craniomaxillofacial growth effect after treatment in many aspects. In the observation duration of treatment group, decrease in ANB, Wits appraisal and BAr-AAr were statistically significant compared to class I control group (p < 0.001), and there was a significant increase in NA-FH (P < 0.001) which was contrary to class III control group. Treatment group presented a significant increase in Gn-Co (P < 0.01) and Co-Go (P < 0.001), except for changes in the extent of the mandibular base (Pog-Go, P = 0.149) compared to class I control group. The vertical maxillomandibular skeletal variables (Gonial; MP-SN; MP-FH; Y-axis) in treatment group decreased significantly compared to those in class III control group (P < 0.01). U1-SN and L1-MP showed a significant increase, which was similar to the class I group (P > 0.05), and overjet decreased significantly relative to both of the two control groups (P < 0.05). CONCLUSION: Maxillary protraction therapy led to stable outcomes in approximately 77.42% of children with Class III malocclusion approximately 2 years after treatment. Unfavorable skeletal changes were mainly due to the greater protrusion of the mandible but maxillary protraction did have a certain degree of postimpact on the mandibular base. Protraction therapy does not fundamentally change the mode of maxillary growth in Class III subjects except for the advancement of the maxilla. Craniomaxillofacial region tend to restabilize after treatment and lead to skeletal growth rotation and more dentoalveolar compensation.
Assuntos
Má Oclusão Classe III de Angle , Má Oclusão , Criança , Humanos , Maxila , Estudos Retrospectivos , Grupos Controle , Cefalometria , Má Oclusão Classe III de Angle/terapia , MandíbulaRESUMO
OBJECTIVE: To understand the prevalence, genetic characteristics and drug resistance features of Salmonella Kentucky ST314 in Shenzhen. METHODS: Whole genome sequencing of 14 strains of Salmonella Kentucky ST314 collected from 2010-2021 by the Foodborne Disease Surveillance Network of Shenzhen Center for Disease Control and Prevention for phylogenetic evolutionary analysis, drug resistance gene and plasmid detection; drug susceptibility experiments were performed by micro-broth dilution method. RESULTS: A total of 57 strains of Salmonella Kentucky were collected from the foodborne disease surveillance network, 14 of which were ST314. The Shenzhen isolates were clustered with isolates from Southeast Asian countries such as Vietnam and Thailand on clade 314.2, and the single nucleotide polymorphism distance between local strains in Shenzhen was large, indicating dissemination. In this study, a total of 17 drug resistance genes/mutations in 9 categories were detected in the genome of Salmonella Kentucky ST314, carrying 3 extended spectrum beta-lactamases(ESBLs), including bla_(CTX-M-24)(14.3%, 2/14), bla_(CTX-M-55)(7.1%, 1/14), and bla_(CTX-M-130)(14.3%, 2/14), all located on plasmids. Regarding quinolone resistance factors, two plasmid-mediated quinolone resistance(PMQR) genes were identified in the genome: qnrB6(71.4%, 10/14) and aac(6')Ib-cr(78.6%, 11/14), a quinolone resistance quinolone resistance-determining regions(QRDR) mutation T57 S(100%, 14/14). The multi-drug resistance rate of Salmonella Kentucky ST314 in Shenzhen was 92.86%(13/14)with the highest rate of resistance to tetracycline and cotrimoxazole(100%, 14/14), followed by chloramphenicol(92.86%, 13/14), cefotaxime and ampicillin(78.57%, 11/14), ciprofloxacin and nalidixic acid(71.43%, 10/14), and ampicillin-sulbactam had the lowest resistance rate(21.43%, 3/14). CONCLUSION: ST314 is the second most prevalent ST type among Salmonella Kentucky in Shenzhen, mainly isolated from food, especially poultry; phylogenetic analysis suggests that ST314 is a disseminated infection and the genome shows a highly genetically conserved phenotype. Drug resistance of Salmonella Kentucky ST314 is very serious, especially QRDR mutation, PMQR gene co-mediated quinolone resistance and plasmid-mediated cephalosporin resistance are prominent and deserve extensive attention.
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Doenças Transmitidas por Alimentos , Quinolonas , Humanos , Kentucky , Filogenia , Salmonella , Antibacterianos/farmacologia , Plasmídeos/genética , Resistência a Medicamentos , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/genética , beta-Lactamases/genéticaRESUMO
Alpha-synuclein (α-syn) is a major component of lewy bodies, which is biomarker of Parkinson's disease (PD). It accumulates in substantia nigra pars compacts (SNpc) to form insoluble aggregates and cause neurotoxicity, which is often accompanied by iron deposition. In this study, we compared the iron reductase activity between monomeric α-syn (M-α-syn) and oligomeric α-syn (O-α-syn), investigated the effect of α-syn on iron metabolism of BV2 microglia cells as well. We found that α-syn had ferric reductase activity, and O-α-syn had stronger enzyme activity than M-α-syn. M-α-syn upregulated iron uptake protein, divalent metal transporter1 (DMT1) expression and iron influx, but did not regulate iron release protein, ferroportin1 (FPN1) expression and iron efflux. O-α-syn elevated the expression of both DMT1 and FPN1, thus increased the iron influx and efflux in BV2 microglial cells, but the expressions of iron regulatory protein1 and hypoxia inducible factor2α have no significant change. Moreover, both M-α-syn and O-α-syn could increase the mRNA expressions of TNF-α and IL-1ß in BV2 microglia cells. Taken together, our data suggest that both types of α-syn can activate microglia, which leads to increased expressions of pro-inflammatory factors. α-syn can affect DMT1 and FPN1 expressions in BV2 microglia cells, which might be through its ferric reductase activity.
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Heme oxygenase-1 (HO-1) is the only way for cells to decompose heme. It can cleave heme to produce carbon monoxide (CO), ferrous iron (Fe2+ ), and biliverdin (BV). BV is reduced to bilirubin (BR) by biliverdin reductase(BVR). In previous studies, HO-1 was considered to have protective effects because of its anti-inflammatory, anti-apoptosis, and antiproliferation functions. However, emerging experimental studies have found that the metabolites derived from HO-1 can cause increase iin intracellular oxidative stress, mitochondrial damage, iron death, and autophagy. Because of its particularity, it is very meaningful to understand its exact mechanism. In this review, we summarized the protective and toxic effects of HO-1, its potential mechanism, its role in neurodegenerative diseases and related drug research. This knowledge may be beneficial to the development of new therapies for neurodegenerative diseases and is crucial to the development of new therapeutic strategies and biomarkers.
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N6-methyladenosine (m6A) plays a key role in many biological processes. However, the function and evolutionary relationship of m6A-related genes in insects remain largely unknown. Here we analysed the phylogeny of m6A-related genes among 207 insect species and found that m6A-related genes are evolutionarily conserved in insects. Subcellular localization experiments of m6A-related proteins in BmN cells confirmed that BmYTHDF3 was localized in the cytoplasm, BmMETTL3, BmMETTL14, and BmYTHDC were localized in the nucleus, and FL2D was localized to both the nucleus and cytoplasm. We examined the expression patterns of m6A-related genes during the embryonic development of Bombyx mori. To elucidate the function of BmMETTL3 during the embryonic stage, RNA sequencing was performed to measure changes in gene expression in silkworm eggs after BmMETTL3 knockdown, as well as in BmN cells overexpressing BmMETTL3. The global transcriptional pattern showed that knockdown of BmMETTL3 affected multiple cellular processes, including oxidoreductase activity, transcription regulator activity, and the cation binding. In addition, transcriptomic data revealed that many observed DEGs were associated with fundamental metabolic processes, including carbon metabolism, purine metabolism, amino acid biosynthesis, and the citrate cycle. Interestingly, we found that knockdown of BmMETTL3 significantly affected Wnt and Toll/Imd pathways in embryos. Taken together, these results suggest that BmMETTL3 plays an essential role in the embryonic development of B. mori, and deepen our understanding of the function of m6A-related genes in insects.
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Bombyx , Animais , Bombyx/genética , Bombyx/metabolismo , Metiltransferases/genética , Regulação da Expressão Gênica , Perfilação da Expressão Gênica , Transcriptoma , Desenvolvimento Embrionário/genéticaRESUMO
Flavonoids and their methylated derivatives have immense market potential in the food and biomedical industries due to their multiple beneficial effects, such as antimicrobial, anti-inflammatory, and anticancer activities. The biological synthesis of flavonoids and their derivatives is often accomplished via the use of genetically modified microorganisms to ensure large-scale production. Therefore, it is pivotal to understand the properties of O-methyltransferases (OMTs) that mediate the methylation of flavonoids. However, the properties of these OMTs are governed by their: sources, substrate specificity, amino acid residues in the active sites, and the intricate mechanism. In order to obtain a clue for the selection of suitable OMTs for the biosynthesis of a target methylated flavonoid, we made a comprehensive review of the currently reported results, with a particular focus on their comparative regioselectivity for different flavonoid substrates. Additionally, the possible mechanisms for the diversity of this class of enzymes were explored using molecular simulation technology. Finally, major gaps in our understanding and areas for future studies were discussed. The findings of this study may be useful in selecting genes that encode OMTs and designing enzyme-based processes for synthesizing O-methylated flavonoids.
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Fungi-mediated synthesis of Gold nanoparticles (AuNPs) has advantages in: high efficiency, low energy consumption, no need for extra capping and stabilizing agents, simple operation, and easy isolation and purification. Many fungi have been found to synthesize AuNPs inside cells or outside cells, providing different composition and properties of particles when different fungi species or reaction conditions are used. This is good to produce AuNPs with different properties, but may cause challenges to precisely control the particle shape, size, and activities. Besides, low concentrations of substrate and fungal biomass are needed to synthesize small-size particles, limiting the yield of AuNPs in a large scale. To find clues for the development methods to solve these challenges, the reported mechanisms of the fungi-mediated synthesis of AuNPs were summarized. The mechanisms of intracellular AuNPs synthesis are dependent on gold ions absorption by the fungal cell wall via proteins, polysaccharides, or electric absorption, and the reduction of gold ions via enzymes, proteins, and other cytoplasmic redox mediators in the cytoplasm or cell wall. The extracellular synthesis of AuNPs is mainly due to the metabolites outside fungal cells, including proteins, peptides, enzymes, and phenolic metabolites. These mechanisms cause the great diversity of the produced AuNPs in functional groups, element composition, shapes, sizes, and properties. Many methods have been developed to improve the synthesis efficiency by changing: chloroauric acid concentrations, reaction temperature, pH, fungal mass, and reaction time. However, future studies are still required to precisely control the: shape, size, composition, and properties of fungal AuNPs.
RESUMO
Decades of spaceflight studies have provided abundant evidence that individual cells in vitro are capable of sensing space microgravity and responding with cellular changes both structurally and functionally. However, how microgravity is perceived, transmitted, and converted to biochemical signals by single cells remains unrevealed. Here in this review, over 40 cellular biology studies of real space fights were summarized. Studies on cells of the musculoskeletal system, cardiovascular system, and immune system were covered. Among all the reported cellular changes in response to space microgravity, cytoskeleton (CSK) reorganization emerges as a key indicator. Based on the evidence of CSK reorganization from space flight research, a possible mechanism from the standpoint of "cellular mechanical equilibrium" is proposed for the explanation of cellular response to space microgravity. Cytoskeletal equilibrium is broken by the gravitational change from ground to space and is followed by cellular morphological changes, cell mechanical properties changes, extracellular matrix reorganization, as well as signaling pathway activation/inactivation, all of which ultimately lead to the cell functional changes in space microgravity.