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Principal component analysis (PCA) is an important and widely used unsupervised learning method that determines population structure based on genetic variation. Genome sequencing of thousands of individuals usually generate tens of millions of SNPs, making it challenging for PCA analysis and interpretation. Here we present VCF2PCACluster, a simple, fast and memory-efficient tool for Kinship estimation, PCA and clustering analysis, and visualization based on VCF formatted SNPs. We implemented five Kinship estimation methods and three clustering methods for its users to choose from. Moreover, unlike other PCA tools, VCF2PCACluster possesses a clustering function based on PCA result, which enabling users to automatically and clearly know about population structure. We demonstrated the same accuracy but a higher performance of this tool in performing PCA analysis on tens of millions of SNPs compared to another popular PLINK2 software, especially in peak memory usage that is independent of the number of SNPs in VCF2PCACluster.
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Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Software , Análise por Conglomerados , HumanosRESUMO
BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.
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Estenose Coronária , Infarto do Miocárdio , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Masculino , Estudos Prospectivos , Infarto do Miocárdio/genética , Pessoa de Meia-Idade , Prognóstico , Estenose Coronária/genética , Adulto , Apolipoproteína A-I/genética , Intervenção Coronária Percutânea , Serina Endopeptidases/genética , Genótipo , Apolipoproteína B-100/genética , Predisposição Genética para DoençaRESUMO
BACKGROUND: Cardiometabolic multimorbidity (CM) is emerging as a global health challenge. This study investigated the potential impact of muscle strength on the risk of CM in middle-aged and older Chinese adults. METHODS: In total, 7610 participants were identified from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength was measured by absolute, relative grip strength (normalized for body mass index) and chair-rising time which were classified into three categories according to tertiles stratified by gender. Cox proportional hazards models were adopted to evaluate the effect of muscle strength on CM. RESULTS: During follow-up, 235(3.76%) participants from none cardiometabolic diseases (CMD), 140 (19.23%) from diabetes, 119 (21.17%) from heart disease, and 22 (30.56%) from stroke progressed to CM. In participants who had low relative grip strength, CM was more likely to occur in individuals with heart disease at baseline (HR: 1.89, 95%CIs: 1.10 to 3.23). Those with high chair-rising time had a higher risk of CM than those with low chair-rising time in the individuals with diabetes (HR: 1.85, 95%CIs:1.20 to 2.86) and with heart disease (HR: 1.67, 95%CIs:1.04 to 2.70). However, we did not observe an association between muscle strength and CM in participants without CMD or with stroke at baseline. CONCLUSIONS: In Chinese middle-aged and older adults, low relative grip strength was associated with a higher risk of CM in individuals with heart disease, while high chair-rising time was associated with a higher risk of CM in individuals with diabetes or heart disease.
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Multimorbidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , China/epidemiologia , Idoso , Força Muscular/fisiologia , Doenças Cardiovasculares/epidemiologia , Força da Mão/fisiologia , Fatores de Risco , Modelos de Riscos Proporcionais , População do Leste AsiáticoRESUMO
Aqueous Zn-based batteries have emerged as compelling candidates for grid-scale energy storage, owing to their intrinsic safety, remarkable theoretical energy density and cost-effectiveness. Nonetheless, the dendrite formation, side reactions, and corrosion on anode have overshadowed their practical applications. Herein, we present an in situ grown carbon network reinforcing Zn matrix anode prepared by powder metallurgy. This carbon network provides an uninterrupted internal electron transport pathway and optimize the surface electric field distribution, thereby enabling highly reversible Zn deposition. Consequently, symmetrical cells demonstrate impressive stability, running for over 880â h with a low voltage hysteresis (≈32â mV). Furthermore, this Zn matrix composite anode exhibits enhanced performance in both the aqueous Zn-ion and the Zn-air batteries. Notably, Zn//MnO2 cells display superior rate capabilities, while Zn-air batteries deliver high power density and impressive Zn utilization rate (84.9 %). This work provides a new idea of powder metallurgy method for modified Zn anodes, showcasing potential for large-scale production.
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MAIN CONCLUSION: Overexpression of JcSEUSS1 resulted in late flowering, reduced flower number, wrinkled kernels, and decreased seed yield in Jatopha curcas, while downregulation of JcSEUSS1 increased flower number and seed production. The seed oil of Jatropha curcas is suitable as an ideal alternative for diesel fuel, yet the seed yield of Jatropha is restricted by its small number of female flowers and low seed setting rate. Therefore, it is crucial to identify genes that regulate flowering and seed set, and hence improve seed yield. In this study, overexpression of JcSEUSS1 resulted in late flowering, fewer flowers and fruits, and smaller fruits and seeds, causing reduced seed production and oil content. In contrast, the downregulation of JcSEUSS1 by RNA interference (RNAi) technology caused an increase in the flower number and seed yield. However, the flowering time, seed number per fruit, seed weight, and size exhibited no obvious changes in JcSEUSS1-RNAi plants. Moreover, the fatty acid composition also changed in JcSEUSS1 overexpression and RNAi plants, the percentage of unsaturated fatty acids (FAs) was increased in overexpression plants, and the saturated FAs were increased in RNAi plants. These results indicate that JcSEUSS1 played a negative role in regulating reproductive growth and worked redundantly with other genes in the regulation of flowering time, seed number per fruit, seed weight, and size.
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Jatropha , Jatropha/genética , Sementes/genética , Frutas/genética , Madeira , Ácidos Graxos , GenitáliaRESUMO
Rice panicles, a major component of yield, are regulated by phytohormones and nutrients. How mineral nutrients promote panicle architecture remains largely unknown. Here, we report that NIN-LIKE PROTEIN3 and 4 (OsNLP3/4) are crucial positive regulators of rice panicle architecture in response to nitrogen (N). Loss-of-function mutants of either OsNLP3 or OsNLP4 produced smaller panicles with reduced primary and secondary branches and fewer grains than wild-type, whereas their overexpression plants showed the opposite phenotypes. The OsNLP3/4-regulated panicle architecture was positively correlated with N availability. OsNLP3/4 directly bind to the promoter of OsRFL and activate its expression to promote inflorescence meristem development. Furthermore, OsRFL activates OsMOC1 expression by binding to its promoter. Our findings reveal the novel N-responsive OsNLP3/4-OsRFL-OsMOC1 module that integrates N availability to regulate panicle architecture, shedding light on how N nutrient signals regulate panicle architecture and providing candidate targets for the improvement of crop yield.
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Oryza , Oryza/metabolismo , Inflorescência/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: Major depressive disorder (MDD) is a type of emotional dysfunction, and its pathogenesis has not been fully elucidated. Specifically, the key molecules in depression-related brain regions involved in this disease and their contributions to this disease are currently unclear. METHODS: GSE53987 and GSE54568 were selected from the Gene Expression Omnibus database. The data were standardized to identify the common differentially expressed genes (DEGs) in the cortex of MDD patients in the 2 datasets. The DEGs were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The STRING database was used to build protein-protein interaction networks, and the cytoHubba plugin was used to identify hub genes. Furthermore, we selected another blood transcriptome dataset that included 161 MDD and 169 control samples to explore the changes in the screened hub genes. Mice were subjected to 4 weeks of chronic unpredictable mild stress to establish an animal model of depression, and the expression of these hub genes in tissues of the prefrontal cortex was then detected by quantitative real time polymerase chain reaction (qRT-PCR). We subsequently predicted the possible posttranscriptional regulatory networks and traditional Chinese medicine according to the hub genes using a few online databases. RESULTS: The analysis identified 147 upregulated genes and 402 downregulated genes were identified in the cortex of MDD patients compared with that of the controls. Enrichment analyses revealed that DEGs were predominantly enriched in synapse-related cell functions, linoleic acid metabolism, and other pathways. Protein-protein interaction analysis identified 20 hub genes based on the total score. The changes in KDM6B, CUX2, NAAA, PHKB, NFYA, GTF2H1, CRK, CCNG2, ACER3, and SLC4A2 in the peripheral blood of MDD patients were consistent with those in the brain. Furthermore, the prefrontal cortex of mice with depressive-like behaviors showed significantly increased Kdm6b, Aridb1, Scaf11, and Thoc2 expression and decreased Ccng2 expression compared with that of normal mice, which was consistent with the results found for the human brain. Potential therapeutic candidates, such as citron, fructus citri, leaves of Panax Notoginseng, sanchi flower, pseudoginseng, and dan-shen root, were selected via traditional Chinese medicine screening. CONCLUSIONS: This study identified several novel hub genes in specific brain regions involved in the pathogenesis of MDD, which may not only deepen our understanding of depression but may also provide new ideas for its diagnosis and treatment.
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Transtorno Depressivo Maior , Humanos , Animais , Camundongos , Transtorno Depressivo Maior/genética , Redes Reguladoras de Genes , Perfilação da Expressão Gênica/métodos , Mapas de Interação de Proteínas , Encéfalo , Biologia Computacional/métodos , Fator de Transcrição TFIIH/genética , Histona Desmetilases com o Domínio Jumonji/genética , Antiportadores de Cloreto-Bicarbonato/genéticaRESUMO
BACKGROUND AND AIMS: Observational epidemiology studies suggested a relationship between the gut microbiome and primary liver cancer. However, the causal relationship remains unclear because of confounding factors and reverse causality. We aimed to explore the causal role of the gut microbiome in the development of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies (GWAS) of the gut microbiome and liver cancer, and sequencing data from a case-control study validated the findings. A 5-cohort GWAS study in Germany (N = 8956) served as exposure, whilst the UK biobank GWAS study (N = 456 348) served as an outcome. The case-control study was conducted at the First Affiliated Hospital of Wenzhou Medical University from December 2018 to October 2020 and included 184 HCC patients, 63 ICC patients and 40 healthy controls. RESULTS: A total of 57 features were available for MR analysis, and protective causal associations were identified for Family_Ruminococcaceae (OR = 0.46 [95% CI, 0.26-0.82]; p = .009) and Genus_Porphyromonadaceae (OR = 0.59 [95% CI, 0.42-0.83]; p = .003) with HCC, and for Family_Porphyromonadaceae (OR = 0.36 [95% CI, 0.14-0.94]; p = .036) and Genus_Bacteroidetes (OR = 0.55 [95% CI, 0.34-0.90]; p = .017) with ICC respectively. The case-control study results showed that the healthy controls had a higher relative abundance of Family_Ruminococcaceae (p = .00033), Family_Porphyromonadaceae (p = .0055) and Genus_Bacteroidetes (p = .021) than the liver cancer patients. CONCLUSIONS: This study demonstrates that Ruminococcaceae, Porphyromonadaceae and Bacteroidetes are related to a reduced risk of liver cancer (HCC or ICC), suggesting potential significance for the prevention and control of liver cancer.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Microbioma Gastrointestinal , Neoplasias Hepáticas , Humanos , Microbioma Gastrointestinal/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Colangiocarcinoma/genética , Ductos Biliares Intra-Hepáticos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Genetic studies, including transcriptomic and proteomics, have provided new insight into revealing mechanisms of IPF. Herein we provided a novel strategy to identify biomarkers by integrative analysis of transcriptomic and proteomic profiles of IPF patients. We examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways associated with immune system activities and inflammatory responses, while DE proteins are related to extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of butyrophilin-like 9 (BTNL9) and plasmolipin (PLLP) and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.
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Butirofilinas/genética , Matriz Extracelular/metabolismo , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Animais , Biomarcadores/análise , Bleomicina/toxicidade , Diferenciação Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Proteoma/genética , Proteômica , RNA-Seq , Transcriptoma/genética , Cicatrização/genéticaRESUMO
A signal amplification system for electrochemical sensing was established by bio-nanohybrid cells (BNC) based on bacterial self-assembly and biomineralization. The BNC was constructed by partially encapsulating a Shewanella oneidensis MR-1 cell with the self-biomineralized iron sulfide nanoparticles. The iron sulfide nanoparticle encapsulated BNCs showed high transmembrane electron transfer efficiency and was explored as a superior redox cycling module. Impressively, by integrating this BNC redox cycling module into the electrochemical sensing system, the output signal was amplified over 260 times compared to that without the BNC module. Uniquely, with this BNC redox cycling system, ultrasensitive detection of riboflavin with an extremely low LOD of 0.2 nM was achieved. This work demonstrated the power of BNC in the area of biosensing and provided a new possibility for the design of a whole cell redox cycling based signal amplification system.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Oxirredução , RiboflavinaRESUMO
Nitrate is an essential nutrient and an important signaling molecule in plants. However, the molecular mechanisms by which plants perceive nitrate deficiency signaling are still not well understood. Here we report that AtNLP7 protein transport from the nucleus to the cytoplasm in response to nitrate deficiency is dependent on the N-terminal GAF domain. With the deletion of the GAF domain, AtNLP7ΔGAF always remains in the nucleus regardless of nitrate availability. AtNLP7 ΔGAF also shows reduced activation of nitrate-induced genes due to its impaired binding to the nitrate-responsive cis-element (NRE) as well as decreased growth like nlp7-1 mutant. In addition, AtNLP7ΔGAF is unable to mediate the reduction of reactive oxygen species (ROS) accumulation upon nitrate treatment. Our investigation shows that the GAF domain of AtNLP7 plays a critical role in the sensing of nitrate deficiency signal and in the nitrate-triggered ROS signaling process.
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Regulação da Expressão Gênica de Plantas , Nitratos , Nitratos/metabolismo , Plantas/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
In phase II oncology trials, two-stage design allowing early stopping for futility and/or efficacy is frequently used. However, this design based on frequentist statistical approaches could not guarantee a high posterior probability of attending the pre-specified clinically interesting rate from a Bayesian perspective. Here, we proposed a new Bayesian design enabling early terminating for efficacy as well as futility. In addition to the clinically uninteresting and interesting response rate, a prior distribution of response rate, the minimum posterior threshold probabilities and the lengths of the highest posterior density intervals were specified in the design. Finally, we defined the feasible design with the highest total effective predictive probability. We studied the properties of the proposed design and applied it to an oncology trial as an example. The proposed design ensured that the observed response rate fell within prespecified levels of posterior probability. The proposed design provides an alternative design to single-arm two-stage trials.
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Ensaios Clínicos Fase II como Assunto , Neoplasias , Projetos de Pesquisa , Teorema de Bayes , Humanos , Oncologia , Neoplasias/tratamento farmacológico , ProbabilidadeRESUMO
BACKGROUND: Postoperative sore throat (POST) is one of the main adverse postoperative outcome after tracheal intubation using double-lumen endobronchial tubes (DLTs). The aim of this study was to investigate the effectiveness and safety of ultrasound (US)-guided block of the internal branch of the superior laryngeal nerve (iSLN) for alleviating POST after intubation of DLTs. METHODS: Patients undergoing thoracic surgery between August 2019 and August 2021 were randomized into two groups depending on whether they received US-guided iSLN block immediately after the operation. In the control group, the patients underwent a thoracic surgery under general anesthesia (GA) with DLTs without any special treatment, while the patients in the experimental group received US-guided iSLN block bilaterally with 2 ml of 0.25% ropivacaine on either side immediately after the operation. The primary outcome was the grading of sore throat at three-time points after the operation, i.e., immediate extubation, 2 h after extubation, and 24 h after extubation. Secondary outcomes included the rate of nausea and vomiting, hoarseness, dyspnea, and choking cough after swallowing saliva at 2 h after extubation. RESULTS: The incidence and severity of sore throat were significantly lower in the experimental group than the control group at all time intervals (all P < 0.01). The rate of nausea and vomiting, hoarseness, dyspnea, and choking cough after swallow saliva at 2 h after extubation had no statistical difference (all P > 0.05). CONCLUSIONS: The use of US-guided iSLN block can be effectively and safely applied to relieve POST after intubation of DLTs on thoracic surgery. TRIAL REGISTRATION: The study protocol was registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , NO. ChiCTR2000032188, 22/04/2020).
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Obstrução das Vias Respiratórias , Faringite , Obstrução das Vias Respiratórias/etiologia , Tosse/etiologia , Dispneia/complicações , Rouquidão/epidemiologia , Rouquidão/etiologia , Humanos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Nervos Laríngeos , Náusea/complicações , Dor/etiologia , Faringite/epidemiologia , Faringite/etiologia , Faringite/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ultrassonografia de Intervenção , VômitoRESUMO
OBJECTIVE: To explore the impact of artificial-intelligence perceptual learning when performing the ultrasound-guided popliteal sciatic block. METHODS: This simulation-based randomized study enrolled residents who underwent ultrasound-guided sciatic nerve block training at the Department of Anesthesiology of Beijing Jishuitan Hospital between January 2022 and February 2022. Residents were randomly divided into a traditional teaching group and an AI teaching group. All residents attended the same nerve block theory courses, while those in the AI teaching group participated in training course using an AI-assisted nerve identification system based on a convolutional neural network instead of traditional training. RESULTS: A total of 40 residents were included. The complication rates of paresthesia during puncture in the first month of clinical sciatic nerve block practice after training were significantly lower in the AI teaching group than in the traditional teaching group [11 (4.12%) vs. 36 (14.06%), P = 0.000093]. The rates of paresthesia/pain during injection were significantly lower in the AI teaching group than in the traditional teaching group [6 (2.25%) vs. 17 (6.64%), P = 0.025]. The Assessment Checklist for Ultrasound-Guided Regional Anesthesia (32 ± 3.8 vs. 29.4 ± 3.9, P = 0.001) and nerve block self-rating scores (7.53 ± 1.62 vs. 6.49 ± 1.85, P < 0.001) were significantly higher in the AI teaching group than in the traditional teaching group. There were no significant differences in the remaining indicators. CONCLUSION: The inclusion of an AI-assisted nerve identification system based on convolutional neural network as part of the training program for ultrasound-guided sciatic nerve block via the popliteal approach may reduce the incidence of nerve paresthesia and this might be related to improved perceptual learning. CLINICAL TRIAL: CHiCTR2200055115 , registered on 1/ January /2022.
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Nervo Isquiático , Ultrassonografia de Intervenção , Humanos , Nervo Isquiático/diagnóstico por imagem , Parestesia/etiologia , Incidência , Inteligência Artificial , InteligênciaRESUMO
Bone mesenchymal stem cell (BMSC)-based regenerative therapy is critical for the craniofacial defect reconstruction. However, oxidative stress microenvironment after transplantation limits the therapeutic efficiency of BMSC. The miR-181c has been found to be associated with cell survival and proliferation. Herein, we investigated whether prior miR-181c treatment promoted BMSC proliferation and survival under oxidative stress injury. The results in our study demonstrated that hydrogen peroxide (H2 O2 ) treatment reduced BMSC viability and this effect could be reversed via additional supplementation of miR181-c. Mechanistically, oxidative stress increased cell apoptosis, augmented caspase-3 activity, promoted reactive oxygen species synthesis, impaired mitochondrial potential, and induced mitochondrial dynamics imbalance. However, miR-181c pretreatment reversed these effects of oxidative stress on BMSC. Moreover, miR-181c treatment improved BMSC proliferation, migration and paracrine, which are very important for craniofacial reconstruction. In addition, we identified that AMP-activated protein kinase (AMPK)-mitofusins-1 (Mfn1) axis was the direct targets of miR-181c in BMSC. Mfn1 silencing impaired the protective effects miR-181c on BMSC viability and proliferation under oxidative stress environment. Collectively, our results indicate that miR-181c participates in oxidative stress-mediated BMSC damage by modulating the AMPK-Mfn1 signaling pathway, suggesting miR-181c-AMPK-Mfn1 axis may serves as novel therapeutic targets to facilitate craniofacial defect reconstruction.
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Apoptose/genética , Sistema de Sinalização das MAP Quinases/genética , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Osso e Ossos/metabolismo , Sobrevivência Celular/genética , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Some patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. METHODS: Sixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n = 9), an improvement group (n = 13), and a stable group (n = 14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed. RESULTS: Compared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = - 0.323, p = 0.018; KL-6: rS = - 0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001). CONCLUSIONS: Serum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.
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Pneumonias Intersticiais Idiopáticas/sangue , Pneumonias Intersticiais Idiopáticas/diagnóstico , Mucina-1/sangue , Proteína A Associada a Surfactante Pulmonar/sangue , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The sputum saccharide chain antigen (Krebs von den Lungen-6 [KL-6]) is a serum biomarker of lung injury. We aimed to evaluate the clinical performance of the automated immunoassay analyzer HISCL-5000 in detecting KL-6 by comparing it with LUMIPULSE G1200 and determine the diagnostic value of KL-6 in interstitial lung disease (ILD). METHODS: A total of 145 serum samples from patients were tested using the two automated immunoassay analyzers in parallel. RESULTS: With a cutoff level of 500 U/mL, comparing the two systems, the agreement, sensitivity, specificity, and kappa value were 99.20%, 100%, 98.63%, and 0.984 (95% CI, 0.952-1.000), respectively. Spearman's correlation and ICC showed that there was a strong correlation between serum KL-6 levels measured by the two systems (rS = .991 [95% CI, 0.981-0.995], ICC = 0.984 [95% CI, 0.978-0.989], P < .01). The clinical diagnosis agreement rate in both systems was >80%. The kappa value was 0.707 (95% CI, 0.582-0.832; SYSTEM B) and 0.707 (95% CI, 0.588-0.826; SYSTEM A). The KL-6 level in the ILD group (1339.5, 662.5-2363) was significantly higher than that in the non-ILD groups (252, 158.5-353; Mann-Whitney U = 381.5, P < .01), and the KL-6 level (1558, 726-2772.5) in the ILD group detected by SYSTEM A was significantly higher than that in the lung cancer group (339, 207-424), other respiratory disease group (249, 194-366), and control group (198, 131.5-297; Kruskal-Wallis H = 63.19, P < .01). CONCLUSIONS: HISCL-5000 showed well-concordant results with those of HISCL-5000 in the KL-6 tests. In patients with ILD, KL-6 showed a good diagnostic performance.
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Imunoensaio/instrumentação , Doenças Pulmonares Intersticiais/diagnóstico , Mucina-1/sangue , Adulto , Idoso , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos RetrospectivosRESUMO
Complex oxide thin-film heterostructures often exhibit magnetic properties different from those known for bulk constituents. This is due to the altered local structural and electronic environment at the interfaces, which affects the exchange coupling and magnetic ordering. The emergent magnetism at oxide interfaces can be controlled by ferroelectric polarization and has a strong effect on spin-dependent transport properties of oxide heterostructures, including magnetic and ferroelectric tunnel junctions. Here, using prototype La2/3Sr1/3MnO3/BaTiO3 heterostructures, we demonstrate that ferroelectric polarization of BaTiO3 controls the orbital hybridization and magnetism at heterointerfaces. We observe changes in the enhanced orbital occupancy and significant charge redistribution across the heterointerfaces, affecting the spin and orbital magnetic moments of the interfacial Mn and Ti atoms. Importantly, we find that the exchange coupling between Mn and Ti atoms across the interface is tuned by ferroelectric polarization from ferromagnetic to antiferromagnetic. Our findings provide a viable route to electrically control complex magnetic configurations at artificial multiferroic interfaces, taking a step toward low-power spintronics.
RESUMO
Context: Bone mesenchymal stem cells (BMSC)-based regenerative therapy is critical for the craniofacial defect reconstruction. However, oxidative stress micro-environment after transplantation limits the therapeutic efficiency of BMSC. The miR-181c has been found to be associated with cell survival and proliferation. Objective: Herein, we investigated whether prior miR-181c treatment promoted BMSC proliferation and survival under oxidative stress injury. Materials and methods: Cells were treated with hydrogen peroxide (H2O2) and then cell viability was determined via MTT assay, TUNEL staining and ELISA. Western blotting and immunofluorescence assay were used to detect those alterations of mitochondrial function. Results: H2O2 treatment reduced BMSC viability and this effect could be reversed via additional supplementation of miR181-c. Mechanistically, oxidative stress increased cell apoptosis, augmented caspase-3 activity, promoted reactive oxygen species (ROS) synthesis, impaired mitochondrial potential, and induced mitochondrial dynamics imbalance. However, miR-181c pretreatment reversed these effects of oxidative stress on BMSC. Moreover, miR-181c treatment improved BMSC proliferation, migration and paracrine, which are very important for craniofacial reconstruction. In addition, we identified that AMPK-Mfn1 axis was the direct targets of miR-181c in BMSC. Mfn1 silencing impaired the protective effects miR-181c on BMSC viability and proliferation under oxidative stress environment. Conclusions: Collectively, our results indicate that miR-181c participates in oxidative stress-mediated BMSC damage by modulating the AMPK-Mfn1 signaling pathway, suggesting miR-181c-AMPK-Mfn1 axis may serves as novel therapeutic targets to facilitate craniofacial defect reconstruction.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Osso e Ossos/citologia , Anormalidades Craniofaciais/patologia , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Proteínas Mitocondriais/metabolismo , Transdução de Sinais , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Regulação para Baixo/genética , Metabolismo Energético , Peróxido de Hidrogênio/metabolismo , MicroRNAs/genética , Estresse Oxidativo , Ratos Sprague-DawleyRESUMO
Context: Although bone mesenchymal stem cells (BMSCs) have been used for the treatment of oral and maxillofacial defects, the survival rate and limited proliferation reduces the therapeutic efficiency of BMSC.Objective: The aim of our study is to explore the role of miR-31 in regulating survival, proliferation, and migration of BMSC in vitro.Materials and methods: LPS was used in vitro to induce BMSC damage and then miR-31 was used to incubate with BMSC. Subsequently, BMSC proliferation, survival, and migration were determined via ELISA, qPCR, western blots, and immunofluorescence.Results: The expression of miR-31 was downregulated in response to LPS stress. Interestingly, supplementation of miR-31 could reverse the survival, proliferation and migration of BMSC under LPS. Mechanically, miR-31 treatment inhibited the activation of caspase, and thus promoted BMSC survival. Besides, miR-31 upregulated the genes related to cell proliferation, an effect that was followed by an increase in the levels of migratory factors. Further, we found that miR-31 treatment activated the CXCR4/Akt pathway and blockade of CXCR4/Akt could abolish the beneficial effects of miR-31 on BMSC proliferation, survival, and migration.Conclusions: miR-31 could increase the therapeutic efficiency of BMSC via the CXCR4/Akt pathway.