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1.
Genes Dev ; 33(13-14): 844-856, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31123065

RESUMO

The Piwi-interacting RNA (piRNA) pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires a specialized machinery that converts long single-stranded precursors into small RNAs of ∼25-nucleotides in length. This process involves factors that operate in two different subcellular compartments: the nuage/Yb body and mitochondria. How these two sites communicate to achieve accurate substrate selection and efficient processing remains unclear. Here, we investigate a previously uncharacterized piRNA biogenesis factor, Daedalus (Daed), that is located on the outer mitochondrial membrane. Daed is essential for Zucchini-mediated piRNA production and the correct localization of the indispensable piRNA biogenesis factor Armitage (Armi). We found that Gasz and Daed interact with each other and likely provide a mitochondrial "anchoring platform" to ensure that Armi is held in place, proximal to Zucchini, during piRNA processing. Our data suggest that Armi initially identifies piRNA precursors in nuage/Yb bodies in a manner that depends on Piwi and then moves to mitochondria to present precursors to the mitochondrial biogenesis machinery. These results represent a significant step in understanding a critical aspect of transposon silencing; namely, how RNAs are chosen to instruct the piRNA machinery in the nature of its silencing targets.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , RNA Helicases/metabolismo , RNA Interferente Pequeno/biossíntese , Animais , Linhagem Celular , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Técnicas de Silenciamento de Genes , Ligação Proteica , Transporte Proteico , RNA Interferente Pequeno/metabolismo
2.
BMC Plant Biol ; 24(1): 105, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342903

RESUMO

BACKGROUND: Nitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes. RESULTS: Total N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar. CONCLUSIONS: N deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.


Assuntos
Panax notoginseng , Plantas Medicinais , Nitrogênio/metabolismo , Plantas Medicinais/genética , Plantas Medicinais/metabolismo , Panax notoginseng/genética , Panax notoginseng/metabolismo , Simulação de Acoplamento Molecular , Melhoramento Vegetal , Aminoácidos/metabolismo , Regulação da Expressão Gênica de Plantas
3.
Mol Phylogenet Evol ; 196: 108084, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38688440

RESUMO

The tribe Collabieae (Epidendroideae, Orchidaceae) comprises approximately 500 species. Generic delimitation within Collabieae are confusing and phylogenetic interrelationships within the Collabieae have not been well resolved. Plastid genomes and nuclear internal transcribed spacer (ITS) sequences were used to estimate the phylogenetic relationships, ancestral ranges, and diversification rates of Collabieae. The results showed that Collabieae was subdivided into nine clades with high support. We proposed to combine Ancistrochilus and Pachystoma into Spathoglottis, merge Collabium and Chrysoglossum into Diglyphosa, and separate Pilophyllum and Hancockia as distinctive genera. The diversification of the nine clades of Collabieae might be associated with the uplift of the Himalayas during the Late Oligocene/Early Miocene. The enhanced East Asian summer monsoon in the Late Miocene may have promoted the rapid diversification of Collabieae at a sustained high diversification rate. The increased size of terrestrial pseudobulbs may be one of the drivers of Collabieae diversification. Our results suggest that the establishment and development of evergreen broadleaved forests facilitated the diversification of Collabieae.


Assuntos
Orchidaceae , Filogenia , Orchidaceae/genética , Orchidaceae/classificação , Florestas , Genomas de Plastídeos/genética , Filogeografia , DNA Espaçador Ribossômico/genética , Análise de Sequência de DNA , Ásia , DNA de Plantas/genética
4.
Gastrointest Endosc ; 99(5): 667-675.e1, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38184117

RESUMO

BACKGROUND AND AIMS: The aim of this study was to determine if utilization of artificial intelligence (AI) in the course of endoscopic procedures can significantly diminish both the adenoma miss rate (AMR) and the polyp miss rate (PMR) compared with standard endoscopy. METHODS: We performed an extensive search of various databases, encompassing PubMed, Embase, Cochrane Library, Web of Science, and Scopus, until June 2023. The search terms used were artificial intelligence, machine learning, deep learning, transfer machine learning, computer-assisted diagnosis, convolutional neural networks, gastrointestinal (GI) endoscopy, endoscopic image analysis, polyp, adenoma, and neoplasms. The main study aim was to explore the impact of AI on the AMR, PMR, and sessile serrated lesion miss rate. RESULTS: A total of 7 randomized controlled trials were included in this meta-analysis. Pooled AMR was markedly lower in the AI group versus the non-AI group (pooled relative risk [RR], .46; 95% confidence interval [CI], .36-.59; P < .001). PMR was also reduced in the AI group in contrast with the non-AI control (pooled RR, .43; 95% CI, .27-.69; P < .001). The results showed that AI decreased the miss rate of sessile serrated lesions (pooled RR, .43; 95% CI, .20 to .92; P < .05) and diminutive adenomas (pooled RR, .49; 95% CI, .26-.93) during endoscopy, but no significant effect was observed for advanced adenomas (pooled RR, .48; 95% CI, .17-1.37; P = .17). The average number of polyps (Hedges' g = -.486; 95% CI, -.697 to -.274; P = .000) and adenomas (Hedges' g = -.312; 95% CI, -.551 to -.074; P = .01) detected during the second procedure also favored AI. However, AI implementation did not lead to a prolonged withdrawal time (P > .05). CONCLUSIONS: This meta-analysis suggests that AI technology leads to significant reduction of miss rates for GI adenomas, polyps, and sessile serrated lesions during endoscopic surveillance. These results underscore the potential of AI to improve the accuracy and efficiency of GI endoscopic procedures.

5.
Dig Dis Sci ; 69(5): 1889-1896, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38517560

RESUMO

AIM: Endoscopic necrosectomy has become the first-line treatment option for infectious necrotizing pancreatitis (INP), especially walled-off necrosis. However, the problems, including operation-related adverse events (AEs) and the need for multiple endoscopic procedures, have not been effectively addressed. We sought to evaluate the clinical safety and efficacy of anhydrous ethanol-assisted endoscopic ultrasound (EUS)-guided transluminal necrosectomy in INP. METHODS: A single-center observational cohort study of INP patients was conducted in a tertiary endoscopic center. Anhydrous ethanol-assisted EUS-guided transluminal necrosectomy (modified group) and conventional endoscopic necrosectomy (conventional group) were retrospectively compared in INP patients. The technical and clinical success rates, operation time, perioperative AEs, postoperative hospital stay, and recurrent INP rates were analyzed, respectively. RESULTS: A total of 55 patients were enrolled. No statistically significant differences were observed between the two groups regarding baseline characteristics. Compared to patients in the conventional group, patients in the modified group demonstrated significantly reduced times of endoscopic transluminal necrosectomies (1.96 ± 0.89 vs. 2.73 ± 0.98; P = 0.004) and comparable perioperative AEs (P = 0.35). Meanwhile, no statistically significant differences were observed in the technical and clinical success rates (P = 0.92), operation time (P = 0.59), postoperative hospital stay (P = 0.36), and recurrent INP rates (P = 1.00) between the two groups. CONCLUSION: Anhydrous ethanol-assisted EUS-guided transluminal necrosectomy seemed safe and effective in treating INP. Compared with conventional endoscopic transluminal necrosectomy, its advantage was mainly in reducing the number of endoscopic necrosectomies without increasing perioperative AEs.


Assuntos
Endossonografia , Etanol , Pancreatite Necrosante Aguda , Humanos , Pancreatite Necrosante Aguda/cirurgia , Pancreatite Necrosante Aguda/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Etanol/administração & dosagem , Endossonografia/métodos , Estudos Retrospectivos , Adulto , Resultado do Tratamento , Idoso , Tempo de Internação/estatística & dados numéricos , Ultrassonografia de Intervenção/métodos , Duração da Cirurgia
6.
J Am Soc Nephrol ; 34(5): 895-908, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36749126

RESUMO

SIGNIFICANCE STATEMENT: Polymorphisms of HLA genes may confer susceptibility to acute tubulointerstitial nephritis (ATIN), but small sample sizes and candidate gene design have hindered their investigation. The first genome-wide association study of ATIN identified two significant loci, risk haplotype DRB1*14-DQA1*0101-DQB1*0503 (DR14 serotype) and protective haplotype DRB1*1501-DQA1*0102-DQB1*0602 (DR15 serotype), with amino acid position 60 in the peptide-binding groove P10 of HLA-DR ß 1 key. Risk alleles were shared among different causes of ATIN and HLA genotypes associated with kidney injury and immune therapy response. HLA alleles showed the strongest association. The findings suggest that a genetically conferred risk of immune dysregulation is part of the pathogenesis of ATIN. BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare immune-related disease, accounting for approximately 10% of patients with unexplained AKI. Previous elucidation of the relationship between genetic factors that contribute to its pathogenesis was hampered because of small sample sizes and candidate gene design. METHODS: We undertook the first two-stage genome-wide association study and meta-analysis involving 544 kidney biopsy-defined patients with ATIN and 2346 controls of Chinese ancestry. We conducted statistical fine-mapping analysis, provided functional annotations of significant variants, estimated single nucleotide polymorphism (SNP)-based heritability, and checked genotype and subphenotype correlations. RESULTS: Two genome-wide significant loci, rs35087390 of HLA-DQA1 ( P =3.01×10 -39 ) on 6p21.32 and rs2417771 of PLEKHA5 on 12p12.3 ( P =2.14×10 -8 ), emerged from the analysis. HLA imputation using two reference panels suggested that HLA-DRB1*14 mainly drives the HLA risk association . HLA-DRB1 residue 60 belonging to pocket P10 was the key amino acid position. The SNP-based heritability estimates with and without the HLA locus were 20.43% and 10.35%, respectively. Different clinical subphenotypes (drug-related or tubulointerstitial nephritis and uveitis syndrome) seemed to share the same risk alleles. However, the HLA risk genotype was associated with disease severity and response rate to immunosuppressive therapy. CONCLUSIONS: We identified two candidate genome regions associated with susceptibility to ATIN. The findings suggest that a genetically conferred risk of immune dysregulation is involved in the pathogenesis of ATIN.


Assuntos
Estudo de Associação Genômica Ampla , Nefrite Intersticial , Humanos , Cadeias HLA-DRB1/genética , Nefrite Intersticial/genética , Genótipo , Cadeias alfa de HLA-DQ/genética , Haplótipos , Alelos , Predisposição Genética para Doença
7.
Int J Mol Sci ; 25(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38338856

RESUMO

Epipogium roseum, commonly known as one of the ghost orchids due to its rarity and almost transparent color, is a non-photosynthetic and fully mycoheterotrophic plant. Given its special nutritional strategies and evolutionary significance, the mitogenome was first characterized, and three plastomes sampled from Asia were assembled. The plastomes were found to be the smallest among Orchidaceae, with lengths ranging from 18,339 to 19,047 bp, and exhibited high sequence variety. For the mitogenome, a total of 414,552 bp in length, comprising 26 circular chromosomes, were identified. A total of 54 genes, including 38 protein-coding genes, 13 tRNA genes, and 3 rRNA genes, were annotated. Multiple repeat sequences spanning a length of 203,423 bp (45.47%) were discovered. Intriguingly, six plastid regions via intracellular gene transfer and four plastid regions via horizontal gene transfer to the mitogenome were observed. The phylogenomics, incorporating 90 plastomes and 56 mitogenomes, consistently revealed the sister relationship of Epipogium and Gastrodia, with a bootstrap percentage of 100%. These findings shed light on the organelle evolution of Orchidaceae and non-photosynthetic plants.


Assuntos
Genomas de Plastídeos , Orchidaceae , Filogenia , Plastídeos , Orchidaceae/genética , Ásia , Evolução Molecular
8.
BMC Genomics ; 24(1): 126, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932328

RESUMO

BACKGROUND: Late embryogenesis abundant (LEA) proteins play an important role in dehydration process of seed maturation. The seeds of Panax notoginseng (Burkill) F. H. Chen are typically characterized with the recalcitrance and are highly sensitive to dehydration. However, it is not very well known about the role of LEA proteins in response to dehydration stress in P. notoginseng seeds. We will perform a genome-wide analysis of the LEA gene family and their transcriptional responses to dehydration stress in recalcitrant P. notoginseng seeds. RESULTS: In this study, 61 LEA genes were identified from the P. notoginseng genome, and they were renamed as PnoLEA. The PnoLEA genes were classified into seven subfamilies based on the phylogenetic relationships, gene structure and conserved domains. The PnoLEA genes family showed relatively few introns and was highly conserved. Unexpectedly, the LEA_6 subfamily was not found, and the LEA_2 subfamily contained 46 (75.4%) members. Within 19 pairs of fragment duplication events, among them 17 pairs were LEA_2 subfamily. In addition, the expression of the PnoLEA genes was obviously induced under dehydration stress, but the germination rate of P. notoginseng seeds decreased as the dehydration time prolonged. CONCLUSIONS: We found that the lack of the LEA_6 subfamily, the expansion of the LEA_2 subfamily and low transcriptional levels of most PnoLEA genes might be implicated in the recalcitrant formation of P. notoginseng seeds. LEA proteins are essential in the response to dehydration stress in recalcitrant seeds, but the protective effect of LEA protein is not efficient. These results could improve our understanding of the function of LEA proteins in the response of dehydration stress and their contributions to the formation of seed recalcitrance.


Assuntos
Panax notoginseng , Panax notoginseng/genética , Panax notoginseng/metabolismo , Desidratação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Sementes/metabolismo , Desenvolvimento Embrionário , Regulação da Expressão Gênica de Plantas
9.
BMC Plant Biol ; 23(1): 67, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36721119

RESUMO

BACKGROUND: Panax notoginseng (Burk) F.H. Chen is an essential plant in the family of Araliaceae. Its seeds are classified as a type of morphophysiological dormancy (MPD), and are characterized by recalcitrance during the after-ripening process. However, it is not clear about the molecular mechanism on the after-ripening in recalcitrant seeds. RESULTS: In this study, exogenous supply of gibberellic acid (GA3) with different concentrations shortened after-ripening process and promoted the germination of P. notoginseng seeds. Among the identified plant hormone metabolites, exogenous GA3 results in an increased level of endogenous hormone GA3 through permeation. A total of 2971 and 9827 differentially expressed genes (DEGs) were identified in response to 50 mg L-1 GA3 (LG) and 500 mg L-1 GA3 (HG) treatment, respectively, and the plant hormone signal and related metabolic pathways regulated by GA3 was significantly enriched. Weighted gene co-expression network analysis (WGCNA) revealed that GA3 treatment enhances GA biosynthesis and accumulation, while inhibiting the gene expression related to ABA signal transduction. This effect was associated with higher expression of crucial seed embryo development and cell wall loosening genes, Leafy Contyledon1 (LEC1), Late Embryogenesis Abundant (LEA), expansins (EXP) and Pectinesterase (PME). CONCLUSIONS: Exogenous GA3 application promotes germination and shorts the after-ripening process of P. notoginseng seeds by increasing GA3 contents through permeation. Furthermore, the altered ratio of GA and ABA contributes to the development of the embryo, breaks the mechanical constraints of the seed coat and promotes the protrusion of the radicle in recalcitrant P. notoginseng seeds. These findings improve our knowledge of the contribution of GA to regulating the dormancy of MPD seeds during the after-ripening process, and provide new theoretical guidance for the application of recalcitrant seeds in agricultural production and storage.


Assuntos
Panax notoginseng , Plantas Medicinais , Reguladores de Crescimento de Plantas , Germinação , Sementes
10.
Mol Phylogenet Evol ; 184: 107797, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37086913

RESUMO

Pleione is an orchid endemically distributed in high mountain areas across the Hengduan Mountains (HDM), Himalayas, Southeast Asia and South of China. The unique flower shapes, rich colors and immense medicinal importance of Pleione are valuable ornamental and economic resources. However, the phylogenetic relationships and evolutionary history of the genus have not yet been comprehensively resolved. Here, the evolutionary history of Pleione was investigated using single-copy gene single nucleotide polymorphisms and chloroplast genome datasets. The data revealed that Pleione could be divided into five clades. Discordance in topology between the two phylogenetic trees and network and D-statistic analyses indicated the occurrence of reticulate evolution in the genus. The evolution could be attributed to introgression and incomplete lineage sorting. Ancestral area reconstruction suggested that Pleione was originated from the HDM. Uplifting of the HDM drove rapid diversification by creating conditions favoring rapid speciation. This coincided with two periods of consolidation of the Asian monsoon climate, which caused the first rapid diversification of Pleione from 8.87 to 7.83 Mya, and a second rapid diversification started at around 4.05 Mya to Pleistocene. The interaction between Pleione and climate changes, especially the monsoons, led to the current distribution pattern and shaped the dormancy characteristic of the different clades. In addition to revealing the evolutionary relationship of Pleione with orogeny and climate changes, the findings of this study provide insights into the speciation and diversification mechanisms of plants in the East Asian flora.


Assuntos
Genoma de Cloroplastos , Plantas , Filogenia , China , Flores
11.
Neurochem Res ; 48(5): 1382-1394, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36460840

RESUMO

BACKGROUND: Ischemic stroke is a very dangerous disease with high incidence, fatality and disability rate in human beings. Massive evidence has indicated that oxidative stress and inflammation are intimately correlated with progression of ischemic stroke. Additionally, LncRNAs were reported to be involved in ischemic stroke. Here, we aim to explore the effects and molecular mechanism of lncRNA OIP5-AS1 on oxidative stress and inflammation in ischemic stroke. METHODS: HMC3 and SH-SY5Y cells were under the condition of oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to establish cell models of ischemic stroke. Commercial kits were employed to detect the indicators of oxidative stress including ROS, MDA and SOD. The expression of OIP5-AS1, miR-155-5p and IRF2BP2 mRNA was determined using RT-qPCR. The protein levels of inflammatory factors including TNF-α, IL-1ß and IL-6 and IRF2BP2 were assessed by western blot and/or ELISA. Luciferase activity assay was employed to validate their correlations among OIP5-AS1, miR-155-5p and IRF2BP2. RESULTS: In OGD/R-induced HMC3 and SH-SY5Y cells, the expression of OIP5-AS1 and IRF2BP2 was reduced while miR-155-5p was elevated. OGD/R induction promoted oxidative stress and inflammatory response in HMC3 and SH-SY5Y cells, while OIP5-AS1 or IRF2BP2 sufficiency as well as miR-155-5p inhibitor attenuated OGD/R-induced these influences. In addition, IRF2BP2 knockdown abolished the suppressive impacts of OIP5-AS1 overexpression on oxidative stress and inflammatory response in OGD/R-induced HMC3 and SH-SY5Y cells. Mechanistically, OIP5-AS1 enhanced IRF2BP2 expression via sponging miR-155-5p. CONCLUSION: OIP5-AS1 suppressed oxidative stress and inflammatory response to alleviate cell injury caused by OGD/R induction in HMC3 and SH-SY5Y cells through regulating miR-155-5p/IRF2BP2 axis, which might offer novel targeted molecules for ischemic stroke therapy.


Assuntos
AVC Isquêmico , MicroRNAs , Neuroblastoma , Humanos , MicroRNAs/metabolismo , Inflamação/genética , Estresse Oxidativo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismo
12.
Phys Chem Chem Phys ; 25(41): 28465-28472, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37846475

RESUMO

The human heat shock protein plays a critical role in various diseases and is an important target for pharmacological modulation. Simulation of conformational changes and free energy profiles of the human heat shock protein derived by the ligand-leaving process is a challenging issue. In this work, steered molecular dynamics simulation was adopted to simulate the ligand-leaving process. Two composite systems of heat shock protein NHSP90 and small molecules 6FJ and 6G7 are selected as research objects. The free energy during the leaving of ligand small molecules is calculated using conventional molecular dynamics simulation, steered molecular dynamics simulation (SMD), and the umbrella sampling method. We found that the a slower pulling velocity (0.001 nm ns-1) will result in 2.19 kcal mol-1, and the umbrella sampling method gives a value of 3.26 kcal mol-1 for the free energy difference for the two systems, which reasonably agrees with experimental results. A faster-pulling velocity (0.01 nm ns-1) leads to a large overestimation of free energy. At the same time, the conformational analysis indicated that the faster pulling velocity may lead to the conformational change of NHSP90, which was proved to be false by the slower pulling velocity and the umbrella sampling method.


Assuntos
Proteínas de Choque Térmico , Simulação de Dinâmica Molecular , Humanos , Ligantes , Termodinâmica
13.
Mol Ther ; 30(2): 714-725, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-34478872

RESUMO

We and others have shown that MPM (micropeptide in mitochondria) regulates myogenic differentiation and muscle development. However, the roles of MPM in cancer development remain unknown. Here we revealed that MPM was downregulated significantly in human hepatocellular carcinoma (HCC) tissues and its decrease was associated with increased metastasis potential and HCC recurrence. Gain- and loss-of-function investigations disclosed that in vitro migration/invasion and in vivo liver/lung metastasis of hepatoma cells were repressed by restoring MPM expression and increased by silencing MPM. Mechanism investigations revealed that MPM interacted with NDUFA7. Mitochondrial complex I activity was inhibited by overexpressing MPM and enhanced by siMPM, and this effect of siMPM was attenuated by knocking down NDUFA7. The NAD+/NADH ratio, which was regulated by complex I, was reduced by MPM but increased by siMPM. Treatment with the NAD+ precursor nicotinamide abrogated the inhibitory effect of MPM on hepatoma cell migration. Further investigations showed that miR-17-5p bound to MPM and inhibited MPM expression. miR-17-5p upregulation was associated with MPM downregulation in HCC tissues. These findings indicate that a decrease in MPM expression may promote hepatoma metastasis by increasing mitochondrial complex I activity and the NAD+/NADH ratio.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Metástase Neoplásica
14.
Sensors (Basel) ; 23(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37177549

RESUMO

The use of artificial intelligence (AI) to detect phishing emails is primarily dependent on large-scale centralized datasets, which has opened it up to a myriad of privacy, trust, and legal issues. Moreover, organizations have been loath to share emails, given the risk of leaking commercially sensitive information. Consequently, it has been difficult to obtain sufficient emails to train a global AI model efficiently. Accordingly, privacy-preserving distributed and collaborative machine learning, particularly federated learning (FL), is a desideratum. As it is already prevalent in the healthcare sector, questions remain regarding the effectiveness and efficacy of FL-based phishing detection within the context of multi-organization collaborations. To the best of our knowledge, the work herein was the first to investigate the use of FL in phishing email detection. This study focused on building upon a deep neural network model, particularly recurrent convolutional neural network (RNN) and bidirectional encoder representations from transformers (BERT), for phishing email detection. We analyzed the FL-entangled learning performance in various settings, including (i) a balanced and asymmetrical data distribution among organizations and (ii) scalability. Our results corroborated the comparable performance statistics of FL in phishing email detection to centralized learning for balanced datasets and low organizational counts. Moreover, we observed a variation in performance when increasing the organizational counts. For a fixed total email dataset, the global RNN-based model had a 1.8% accuracy decrease when the organizational counts were increased from 2 to 10. In contrast, BERT accuracy increased by 0.6% when increasing organizational counts from 2 to 5. However, if we increased the overall email dataset by introducing new organizations in the FL framework, the organizational level performance improved by achieving a faster convergence speed. In addition, FL suffered in its overall global model performance due to highly unstable outputs if the email dataset distribution was highly asymmetric.

15.
Nano Lett ; 22(15): 6091-6097, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35877983

RESUMO

Skyrmion racetrack memories are highly attractive for next-generation data storage technologies. Skyrmions are noncollinear spin textures stabilized by chiral interactions. To achieve a fast-operating memory device, it is critical to move skyrmions at high speeds. The skyrmion dynamics induced by spin-orbit torques (SOTs) in the commonly studied ferromagnetic films is hindered by strong pinning effects and a large skyrmion Hall effect causing deflection of the skyrmion toward the racetrack edge, which can lead to information loss. Here, we investigate the current-induced nucleation and motion of skyrmions in ferrimagnetic Pt/CoGd/(W or Ta) thin films. We first reveal field-free skyrmion nucleation mediated by Joule heating. We then achieve fast skyrmion motion driven by SOTs with velocities as high as 610 m s-1 and a small skyrmion Hall angle |θSkHE| ≲ 3°. Our results show that ferrimagnets are better candidates for fast skyrmion-based memory devices with low risk of information loss.

16.
Plant J ; 106(3): 801-816, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33595139

RESUMO

Elucidating the biochemical and molecular basis of premature abscission in fruit crops should help develop strategies to enhance fruit set and yield. Here, we report that LcERF2 contributes to differential abscission rates and responses to ethylene in Litchi chinensis (litchi). Reduced LcERF2 expression in litchi was observed to reduce fruit abscission, concurrent with enhanced pedicel growth and increased levels of hexoses, particularly galactose, as well as pectin abundance in the cell wall. Ecoptic expression of LcERF2 in Arabidopsis thaliana caused enhanced petal abscission, together with retarded plant growth and reduced pedicel galactose and pectin contents. Transcriptome analysis indicated that LcERF2 modulates the expression of genes involved in cell wall modification. Yeast one-hybrid, dual-luciferase reporter and electrophoretic mobility shift assays all demonstrated that a UDP-glucose-4-epimerase gene (LcUGE) was the direct downstream target of LcERF2. This result was further supported by a significant reduction in the expression of the A. thaliana homolog AtUGE2-4 in response to LcERF2 overexpression. Significantly reduced pedicel diameter and enhanced litchi fruit abscission were observed in response to LcUGE silencing. We conclude that LcERF2 mediates fruit abscission by orchestrating cell wall metabolism, and thus pedicel growth, in part by repressing the expression of LcUGE.


Assuntos
Parede Celular/metabolismo , Frutas/metabolismo , Litchi/metabolismo , Proteínas de Plantas/metabolismo , UDPglucose 4-Epimerase/metabolismo , Arabidopsis , Ensaio de Desvio de Mobilidade Eletroforética , Frutas/enzimologia , Frutas/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Genes de Plantas/genética , Litchi/enzimologia , Litchi/crescimento & desenvolvimento , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , UDPglucose 4-Epimerase/genética
17.
BMC Microbiol ; 22(1): 36, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-35093006

RESUMO

The human gut is a reservoir of antibiotic resistance genes (ARGs). Even in the absence of antibiotics, ARGs are present in large quantities in faeces of adults, children and even newborns. However, where and when ARGs are acquired remains unclear, as does the types of ARGs acquired. Herein, we recruited 82 pairs of women and their caesarean section newborns. Conventional culture methods and quantitative PCR were employed to detect nine species and six ARG types in meconia, faeces from 3-day-old newborns, amniotic fluid, colostrum, and hospital ward air samples. Furthermore, ARG transfer was explored by tracking Staphylococcus epidermidis isolated from faeces of 3-day-old newborns, colostrum and ward air samples using multi-locus sequence typing (MLST). No ARGs or microorganisms were detected in meconia or amniotic fluid. One or more ARGs were detected in 90.2% of faeces from 3-day-old newborns, and the mecA gene exhibited the highest detection rate (45.1%). ARGs were detected in 85.4% of colostra consistent with ARGs in faeces from 3-day-old newborns. Some ARGs were detected in ward air, and might also be a source of ARGs in neonatal faeces. Isolation of S. epidermidis from neonatal faeces was consistent with antibiotic resistance and gene profiles for colostrum samples. Traceability analysis of S. epidermidis showed that ARGs in neonatal faeces mainly originated from colostrum, and partly from ward air. After birth, neonates born by caesarean section obtain a variety of ARGs mainly from colostrum, and partly from ward air.


Assuntos
Microbiologia do Ar , Bactérias/efeitos dos fármacos , Aleitamento Materno/estatística & dados numéricos , Cesárea/estatística & dados numéricos , Resistência Microbiana a Medicamentos/genética , Trato Gastrointestinal/efeitos dos fármacos , Genes Bacterianos/genética , Leite Humano , Adulto , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Técnicas de Tipagem Bacteriana , Fezes/microbiologia , Feminino , Trato Gastrointestinal/microbiologia , Hospitais , Humanos , Recém-Nascido , Masculino , Mães/estatística & dados numéricos , Tipagem de Sequências Multilocus , Gravidez
18.
J Arthroplasty ; 37(10): 2076-2081, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537614

RESUMO

BACKGROUND: The aim of this study was to evaluate the diagnostic performance of minor criteria from the 2018 International Consensus Meeting (ICM) for the diagnosis of chronic periprosthetic joint infection (PJI) in an Asian population. METHODS: We retrospectively reviewed 76 patients who underwent a revision knee or hip arthroplasty at an academic institution between September 2018 and December 2019. All major and minor 2018 ICM criteria were available for all patients included. Cases with at least 1 major criterion or score ≥6 in minor criteria were considered as infected. The diagnostic performance was evaluated by a receiver operative characteristic curve analysis and area under the curve (AUC) for each minor criterion. An AUC value of more than 0.9 was considered outstanding and 0.8-0.9 as excellent. RESULTS: When using 2018 ICM threshold, the diagnostic performance ranked based on AUC was the following: alpha defensin (0.92), positive histology (0.83), leukocyte esterase (0.82), synovial white blood cell (0.81), serum erythrocyte sedimentation rate (0.78), synovial polymorphonuclear neutrophils (0.77), serum C-reactive protein (0.74), D-dimer (0.59), single positive culture (0.53), and positive intraoperative purulence (0.51). Alpha defensin was considered as an outstanding test among the 2018 ICM minor criteria. Positive histology, leukocyte esterase, and synovial white blood cell were considered as excellent tests. CONCLUSION: Based on our findings, alpha-defensin has the best diagnostic performance in Asian population among the minor criteria of 2018 ICM.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , alfa-Defensinas , Artrite Infecciosa/diagnóstico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Biomarcadores , Proteína C-Reativa/análise , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/metabolismo , Estudos Retrospectivos , Sensibilidade e Especificidade , Líquido Sinovial/química , alfa-Defensinas/metabolismo
19.
J Arthroplasty ; 37(10): 2063-2070, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35490978

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a debilitating disease that primarily affects the hips of young adults. The purpose of this study is to report the mid-term results of impaction bone grafting augmented with a wire coil using the lightbulb technique for ONFH. METHODS: From 1998 to 2016, 50 hips with late precollapsed or early postcollapsed ONFH (28 hips with Association Research Circulation Osseous [ARCO] IIC and 22 with IIIA) were treated by impaction bone grafting augmented with a wire coil using the lightbulb technique. The survival rate was analyzed with conversion to total hip arthroplasty (THA) as the end point. RESULTS: Thirty-one of the 50 hips had a successful clinical result without conversion to THA at a mean follow-up of 109.2 months. The 5-year survival rate was 68%, 82.1%, and 50% for the entire cohort, ARCO stage IIC, and ARCO stage IIIA, respectively. The 19 hips that had failed were converted to THA at an average of 52.8 months. The multivariable Cox proportional hazards model showed that an ARCO stage IIIA disease, a lateral lesion, and a necrotic index ≥0.67 were the independent risk factors for conversion to THA. CONCLUSION: As a head-preserving procedure, the lightbulb technique using impaction bone grafting augmented with a wire coil is worthwhile for patients in an earlier stage of disease and smaller lesion size to postpone the need for THA.


Assuntos
Artroplastia de Quadril , Necrose da Cabeça do Fêmur , Artroplastia de Quadril/métodos , Transplante Ósseo/métodos , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/cirurgia , Seguimentos , Quadril/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
J Arthroplasty ; 37(7): 1375-1382, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35276273

RESUMO

BACKGROUND: Arthroplasty patients with prior septic arthritis are at a high risk of developing periprosthetic joint infection (PJI). The aims of this study are to investigate the outcome and predictors of septic failure following total joint arthroplasty (TJA) for prior septic arthritis. In addition, the optimal timing of TJA is also discussed. METHODS: A retrospective review of 105 TJA patients with prior septic arthritis between January 2000 and December 2019 was performed. Patient-specific and surgery-related factors, organism profiles, and other relevant variables were recorded. RESULTS: At a mean follow-up of 10.3 years, the PJI rate was 16.2%. The adjusted Cox proportional hazards model showed that male gender (HR, 9.95; P < .01), end-stage renal disease (HR, 37.34; P < .01), debridement surgery ≥3 times (HR,4.75; P = .04) and polymicrobial infection in primary septic arthritis (HR, 10.02; P = .02) were independent risk factors for PJI. Neither the types of initial debridement, nor one-stage vs two-stage arthroplasty was related to the risk of PJI. While delaying the timing of TJA did not correlate with a reduction of PJI rate, there was a higher risk of PJI re-infection by the same microorganisms isolated in prior septic arthritis if TJA was performed within 6 months after septic arthritis. CONCLUSIONS: Our study demonstrated that male gender, end-stage renal disease (ESRD), multiple debridement surgeries and polymicrobial septic arthritis predisposed septic failure of TJA following prior septic arthritis. Surgeons should counsel patients with the potential complications, and be cognizant about the risk factors pertaining to septic failure when considering TJA.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Falência Renal Crônica , Infecções Relacionadas à Prótese , Artrite Infecciosa/complicações , Artrite Infecciosa/cirurgia , Artroplastia/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Articulação do Joelho/cirurgia , Masculino , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Estudos Retrospectivos , Fatores de Risco
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