RESUMO
The risk of congenital heart defects (CHDs) may be influenced by maternal genes, fetal genes, and their interactions. Existing methods commonly test the effects of maternal and fetal variants one-at-a-time and may have reduced statistical power to detect genetic variants with low minor allele frequencies. In this article, we propose a gene-based association test of interactions for maternal-fetal genotypes (GATI-MFG) using a case-mother and control-mother design. GATI-MFG can integrate the effects of multiple variants within a gene or genomic region and evaluate the joint effect of maternal and fetal genotypes while allowing for their interactions. In simulation studies, GATI-MFG had improved statistical power over alternative methods, such as the single-variant test and functional data analysis (FDA) under various disease scenarios. We further applied GATI-MFG to a two-phase genome-wide association study of CHDs for the testing of both common variants and rare variants using 947 CHD case mother-infant pairs and 1306 control mother-infant pairs from the National Birth Defects Prevention Study (NBDPS). After Bonferroni adjustment for 23,035 genes, two genes on chromosome 17, TMEM107 (p = 1.64e-06) and CTC1 (p = 2.0e-06), were identified for significant association with CHD in common variants analysis. Gene TMEM107 regulates ciliogenesis and ciliary protein composition and was found to be associated with heterotaxy. Gene CTC1 plays an essential role in protecting telomeres from degradation, which was suggested to be associated with cardiogenesis. Overall, GATI-MFG outperformed the single-variant test and FDA in the simulations, and the results of application to NBDPS samples are consistent with existing literature supporting the association of TMEM107 and CTC1 with CHDs.
Assuntos
Estudo de Associação Genômica Ampla , Cardiopatias Congênitas , Feminino , Humanos , Modelos Genéticos , Genótipo , Cardiopatias Congênitas/genética , Mães , Estudos de Casos e ControlesRESUMO
BACKGROUND: Cancer stem cells (CSCs) are a small subpopulation of tumor cells with the capability of self-renewal and drug resistance, leading to tumor progression and disease relapse. Our study aimed to investigate the antitumor effect of berbamine, extracted from berberis amurensis, on prostate CSCs. METHODS: Sphere formation was used to collect prostate CSCs. The viability, proliferation, invasion, migration, and apoptosis assays were used to evaluate the antitumor effect of berbamine on prostate CSCs. Prostate CSC markers were analyzed by flow cytometry and qRT-PCR. Small RNA sequencing analysis was conducted to analyse miRNAs. Exosomes were extracted using the ExoQuick-TC kit and verified by testing exosomal markers using western blot. RESULTS: Berbamine targets prostate CSCs. Additionally, berbamine enhanced the antitumor effect of cabazitaxel, a second-line chemotherapeutic drug for advanced prostate cancer, and re-sensitized Cabazitaxel-resistant PCa cells (CabaR-DU145) to cabazitaxel by inhibiting ABCG2, CXCR4, IGF2BP1, and p-STAT3. Berbamine enhanced the expression of let-7 miRNA family and miR-26b and influenced the downstream targets IGF2BP1 and p-STAT3, respectively. Silencing CXCR4 and ABCG2 downregulated the expression of IGF2BP1 and p-STAT3, respectively. Importantly, berbamine enhanced also levels of exosomal let-7 family and miR-26b, suggesting that berbamine possibly influences the expression of let-7 family and miR-26b through exosome delivery. Exosomes derived from berbamine-treated CabaR-DU145 cells re-sensitized the cells to cabazitaxel. CONCLUSION: Berbamine enhanced the toxic activity of cabazitaxel and reversed cabazitaxel resistance potentially through CXCR4/exosomal let-7/IGF2BP1 and ABCG2/exosomal miR-26b/p-STAT3 axes.
Assuntos
Exossomos , MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Apoptose , Células-Tronco Neoplásicas/metabolismo , Proliferação de Células , Exossomos/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.
RESUMO
DNA methylation may be regulated by genetic variants within a genomic region, referred to as methylation quantitative trait loci (mQTLs). The changes of methylation levels can further lead to alterations of gene expression, and influence the risk of various complex human diseases. Detecting mQTLs may provide insights into the underlying mechanism of how genotypic variations may influence the disease risk. In this article, we propose a methylation random field (MRF) method to detect mQTLs by testing the association between the methylation level of a CpG site and a set of genetic variants within a genomic region. The proposed MRF has two major advantages over existing approaches. First, it uses a beta distribution to characterize the bimodal and interval properties of the methylation trait at a CpG site. Second, it considers multiple common and rare genetic variants within a genomic region to identify mQTLs. Through simulations, we demonstrated that the MRF had improved power over other existing methods in detecting rare variants of relatively large effect, especially when the sample size is small. We further applied our method to a study of congenital heart defects with 83 cardiac tissue samples and identified two mQTL regions, MRPS10 and PSORS1C1, which were colocalized with expression QTL in cardiac tissue. In conclusion, the proposed MRF is a useful tool to identify novel mQTLs, especially for studies with limited sample sizes.
Assuntos
Biologia Computacional/métodos , Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Locos de Características Quantitativas , Algoritmos , Alelos , Teorema de Bayes , Biologia Computacional/normas , Ilhas de CpG , Análise de Dados , Epigenômica/normas , Genótipo , Humanos , Especificidade de Órgãos/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
MOTIVATION: CpG sites within the same genomic region often share similar methylation patterns and tend to be co-regulated by multiple genetic variants that may interact with one another. RESULTS: We propose a multi-trait methylation random field (multi-MRF) method to evaluate the joint association between a set of CpG sites and a set of genetic variants. The proposed method has several advantages. First, it is a multi-trait method that allows flexible correlation structures between neighboring CpG sites (e.g. distance-based correlation). Second, it is also a multi-locus method that integrates the effect of multiple common and rare genetic variants. Third, it models the methylation traits with a beta distribution to characterize their bimodal and interval properties. Through simulations, we demonstrated that the proposed method had improved power over some existing methods under various disease scenarios. We further illustrated the proposed method via an application to a study of congenital heart defects (CHDs) with 83 cardiac tissue samples. Our results suggested that gene BACE2, a methylation quantitative trait locus (QTL) candidate, colocalized with expression QTLs in artery tibial and harbored genetic variants with nominal significant associations in two genome-wide association studies of CHD. AVAILABILITY AND IMPLEMENTATION: https://github.com/chenlyu2656/Multi-MRF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Metilação , Fenótipo , Genômica/métodos , Metilação de DNA , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Serine protease inhibitor B7 (SERPINB7) mutations have been reported to cause Nagashima-type palmoplantar keratosis (NPPK), but their biological effects are largely unknown. We conducted whole-exome sequencing and identified a c.796C>T (p.Arg266Ter) mutation in SERPINB7 in a Chinese pedigree, which presented as an autosomal recessive inheritance pattern. We assessed the function of SERPINB7 in homozygous and heterozygous mutation carriers, and the results suggested that the single c.796C>T mutation may alter the subcellular localization of SERPINB7. One of the homozygous mutation patients (II-3) was treated with ixekizumab and showed moderate improvement in keratinization. In addition, we analysed the spatiotemporal expression of serpinb1l1 and serpinb1l3, the zebrafish homologue of human SERPINB7, which is expressed in larvae and adults. In larvae, both serpinb1l1 and serpinb1l3 were expressed in the digestive tract. Then, we performed RT-PCR on adult fins based on similarity to the site of NPPK expression in humans and found that the genes were expressed in five fins (pectoral, pelvic, dorsal, anal and caudal) of the zebrafish distal extremity. Taken together, our results demonstrated that the single c.796C>T (p.Arg266Ter) mutation may alter the location of SERPINB7-encoded protein in the skin, while zebrafish SERPINB7 homologue was expressed in adult fins. These findings will enable us to construct knock-out models to explore the pathogenesis of palmoplantar keratosis.
Assuntos
Ceratodermia Palmar e Plantar , Serpinas , Adulto , Animais , Humanos , Inibidores de Serina Proteinase , Peixe-Zebra/genética , Mutação , Serpinas/genética , Linhagem , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologiaRESUMO
BACKGROUND: Patients with sickle cell disease (SCD) frequently undergo prophylactic red blood cell (RBC) exchange transfusion and simple transfusion (RCE/T) to prevent complications of disease, such as stroke. These treatment procedures are performed with a target hemoglobin S (HbS) of ≤30%, or a goal of maintaining an HbS level of <30% immediately prior to the next transfusion. However, there is a lack of evidence-based instructions for how to perform RCE/T in a way that will result in an HbS value <30% between treatments. PRINCIPAL OBJECTIVE: To determine whether targets for post-treatment HbS (post-HbS) or post-treatment HCT (post-HCT) can help to maintain an HbS <30% or <40% between treatments. MATERIALS AND METHODS: We performed a retrospective study of patients with SCD treated with RCE/T at Montefiore Medical Center from June 2014 to June 2016. The analysis included patients of all ages, and data including 3 documented parameters for each RCE/T event: post-HbS, post-HCT, and follow-up HbS (F/u-HbS), which is the pre-treatment HbS prior to the next RCE/T. Generalized linear mixed model was used for estimating the association between post-HbS or post-HCT levels and F/u-HbS <30%. RESULTS: Based on our results, targeting post-HbS ≤10% was associated with higher odds of having events of F/u-HbS <30% between monthly treatments. Targeting post-HbS ≤15% was associated with higher odds of events of F/u-HbS < 40%. As compared to post-HCT ≤30%, a post-HCT >30%-36% did not contribute to more F/u-HbS <30% or HbS <40% events. CONCLUSIONS: For patients with SCD undergoing regular RCE/T for stroke prevention, a post-HbS ≤10% can be used as a goal to help maintain an HbS <30% for 1 month, and a post-HbS ≤15% allowed patients to maintain HbS <40%.
RESUMO
Dairy farming is the most important economic activity in animal husbandry. Mastitis is the most common disease in dairy cattle and has a significant impact on milk quality and yield. The natural extract allicin, which is the main active ingredient of the sulfur-containing organic compounds in garlic, has anti-inflammatory, anticancer, antioxidant, and antibacterial properties; however, the specific mechanism underlying its effect on mastitis in dairy cows needs to be determined. Therefore, in this study, whether allicin can reduce lipopolysaccharide (LPS)-induced inflammation in the mammary epithelium of dairy cows was investigated. A cellular model of mammary inflammation was established by pretreating bovine mammary epithelial cells (MAC-T) with 10 µg/mL LPS, and the cultures were then treated with varying concentrations of allicin (0, 1, 2.5, 5, and 7.5 µM) added to the culture medium. MAC-T cells were examined using RT-qPCR and Western blotting to determine the effect of allicin. Subsequently, the level of phosphorylated nuclear factor kappa-B (NF-κB) was measured to further explore the mechanism underlying the effect of allicin on bovine mammary epithelial cell inflammation. Treatment with 2.5 µM allicin considerably decreased the LPS-induced increase in the levels of the inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in cow mammary epithelial cells. Further research revealed that allicin also inhibited the phosphorylation of inhibitors of nuclear factor kappa-B-α (IκB-α) and NF-κB p65. In mice, LPS-induced mastitis was also ameliorated by allicin. Therefore, we hypothesize that allicin alleviated LPS-induced inflammation in the mammary epithelial cells of cows probably by affecting the TLR4/NF-κB signaling pathway. Allicin will likely become an alternative to antibiotics for the treatment of mastitis in cows.
Assuntos
Dissulfetos , Mastite Bovina , NF-kappa B , Ácidos Sulfínicos , Animais , Bovinos , Feminino , Camundongos , Dissulfetos/uso terapêutico , Células Epiteliais/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Mastite Bovina/tratamento farmacológico , NF-kappa B/metabolismo , Transdução de Sinais , Ácidos Sulfínicos/uso terapêutico , Receptor 4 Toll-Like/metabolismoRESUMO
Emerging evidence from research or clinical studies reported that ABCG2 (ATP-binding cassette sub-family G member 2) interrelates with multidrug resistance (MDR) development in cancers. However, no comprehensive pan-cancer analysis is available at present. Therefore, we explore multiple databases, such as TCGA to investigate the potential therapeutic roles of ABCG2 across 33 different tumors. ABCG2 is expressed on a lower level in most cancers and shows a protective effect. For example, a lower expression level of ABCG2 was detrimental to the survival of adrenocortical carcinoma (TCGA-ACC), glioblastoma multiforme (GBM), and kidney renal clear cell carcinoma (KIRC) patients. Distinct associations exist between ABCG2 expression and stemness scores, microenvironmental scores, microsatellite instability (MSI), and tumor mutational burden (TMB) of tumor patients. We observed a significant positive correlation between the ABCG2 mutation site and prognosis in uterine corpus endometrial carcinoma (UCEC) patients. Moreover, transmembrane transporter activity and hormone biosynthetic-associated functions were found to be involved in the functionality of ABCG2 and its related genes. The cDNAs of cancer cell lines were collected to detect exon mutation sequences and to analyze ABCG2 mRNA expression. The mRNA expression level of ABCG2 showed a significant difference among spheres and drug-resistant cancer cell lines compared with their corresponding adherent cancer cell lines in six types of cancer. This pan-cancer study provides, for the first time, a comprehensive understanding of the multifunctionality of ABCG2 and unveils further details of the potential therapeutic role of ABCG2 in pan-cancer.
Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Carcinoma de Células Renais/genética , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Neoplasias/genética , RNA MensageiroRESUMO
Intense organic neodymium (Nd3+) emission is obtained with near-infrared (NIR) emission equivalent in intensity to that of an organic semiconductor emitting material. The advantage of Nd3+ emission is its narrow line width and NIR emission, which is enhanced by â¼3000 times at low excitation power through an efficient sensitization effect from a composite organic sensitizer. This performance is optimized at high concentrations of Nd3+ ions, and the organic perfluorinated system provides the ion excitations with a quantum efficiency of â¼40%. The material system is applicable to thin films that are compatible with integrated optics applications.
RESUMO
OBJECTIVES: Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. However, little is known about the role of DSCR1 in CRC progression. The present study aimed to elucidate the clinicopathological significance, prognostic, and function roles of DSCR1 in CRC. METHODS: Firstly, we analyzed DSCR1 expression in 58 paired CRC samples and Oncomine database. Then, we analyzed DSCR1 expression in two independent CRC cohorts (test cohort: n = 70; validation cohort: n = 58) and tested its overall survival (OS) by Kaplan-Meier survival analyses. Finally, we overexpressed DSCR1 in two CRC cell lines DLD1 and LoVo and analyzed its effect on cell cycle and senescence. RESULTS: DSCR1 expression was significantly decreased in CRC samples and associated with clinicopathologic features of CRC patients, such as tumor size, lymph node metastasis, and TNM stage. CRC patients with low expression of DSCR1 had shorter overall survival (OS). Kaplan-Meier survival analyses showed that the expression of DSCR1 was significant factor for OS in both cohorts. Multiple Cox regression analysis showed that DSCR1 expression was an independent prognostic marker for OS in test cohort. Overexpression of DSCR1 isoform 4 (DSCR1-4) increased p21, p16, p-NFAT1, and p-NFAT2, while decreased CDK2, CDK4, and Cyclin D1 in CRC cells. In addition, overexpression of DSCR1-4 prevented proliferation and colony formation, and induced senescence in vitro. Moreover, overexpression of DSCR1-4 inhibited tumor growth and tumor angiogenesis in vivo. CONCLUSIONS: Our study found high expression of DSCR1 contributes to favorable prognosis of CRC patients and prevents cell cycle and proliferation of CRC cells, indicating a critical tumor suppressive role in CRC progression.
Assuntos
Neoplasias Colorretais , Síndrome de Down , Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , PrognósticoRESUMO
BACKGROUND: Although growing, the prevalence of the use of health information technology (HIT) by patients to communicate with their providers is not well understood on the population level, nor whether patients are communicating with their providers about their use of HIT. OBJECTIVE: To understand whether patients are communicating with their providers about HIT use and the patient characteristics associated with the communication. DESIGN: Cross-sectional, self-administered survey of a sample of patients across the state of Indiana. PARTICIPANTS: Nine hundred seventy adult participants from across Indiana, 54% female and 79.5% white. MAIN MEASURES: The survey included sections assessing health information-seeking behavior, use of health information technology, and discussions with doctors about the use of HIT. KEY RESULTS: The survey had a 12% response rate. Sixty-three percent of respondent reported going to the Internet as the first source when seeking health information, while only 19% of respondent reported their doctor was their first source. When communicating with doctors electronically, 31% reported using an electronic health record messaging system, 24% used email, and 18% used text messaging. Only 39% of respondents reported having had any conversation about HIT use with their providers. CONCLUSIONS: There remain many unmet opportunities for patients and providers to communicate about HIT use. More guidance for patients and care teams may both help facilitate these conversations and promote optimal use, such as recommendations to ask simple clarification questions and minimize inefficient, synchronous communication when unnecessary.
Assuntos
Comunicação , Informática Médica , Adulto , Estudos Transversais , Correio Eletrônico , Feminino , Humanos , Indiana , Comportamento de Busca de Informação , Internet , MasculinoRESUMO
Microarray technique is a prevalent method for the classification and prediction of colorectal cancer (CRC). Nevertheless, microarray data suffers from the curse of dimensionality when selecting feature genes of the disease based on imbalance samples, thus causing low prediction accuracy. Hence, it is of vital significance to build proper models that can avoid the above problems and predict the CRC more accurately. In this paper, we use an ensemble model to classify samples into healthy and CRC groups and improve prediction performance. The proposed model is composed of three functional modules. The first module mainly performs the function of removing redundant genes. The main feature genes are selected using minimum redundancy maximum relevance (mRMR) method to reduce the dimensionality of features thereby increasing the prediction results. The second module aims to solve the problem caused by imbalanced data using hybrid sampling algorithm RUSBoost. The third module focuses on the classification algorithm optimization. We use mixed kernel function (MKF) based support vector machine (SVM) model to classify an unknown sample into healthy individuals and CRC patients, and then, the Whale Optimization Algorithm (WOA) is applied to find most optimal parameters of the proposed MKF-SVM. The final results show that the proposed model achieves higher G-means than other comparable models. The conclusion comes to show that RUSBoost wrapping WOAâ¯+â¯MKF-SVM model can be applied to improve the predictive performance of colorectal cancer based on the imbalanced data.
Assuntos
Algoritmos , Neoplasias Colorretais/diagnóstico , Perfilação da Expressão Gênica/métodos , Máquina de Vetores de Suporte , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Humanos , Software , Transcriptoma/genéticaRESUMO
To perform a systematic review of the relevant literature about clinical trials on efficacy and safety of immune checkpoint inhibition, whether it is used alone, in combination or with other targeted therapies in patients with advanced and metastatic renal cell carcinoma (RCC), two team members reviewed the abstracts and selected pertinent articles from the relevant databases. A narrative review of randomized controlled trials was performed and seven randomized controlled trials were identified in this systematic review. In treatment of RCC, nivolumab has superior efficacy and safety compared with second-line everolimus. Combination strategies, especially those combined with anti-VEGF agents presents better efficacy but worse outcomes in term of safety than monotherapy and conventional treatment and might guide treatment choice for patients with RCC.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Terapia de Alvo Molecular , Animais , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Resultado do TratamentoRESUMO
In the thermal analysis, the pyrolysis characteristics of crude Kansui Radix, alcohol extract of Kansui Radix, petroleum ether extract, chloroform extract, ethyl acetate extract, n-butanol extract, and licorice vinegar were analyzed with simulated air (N2-O2 4:1) as the carrier gas, at a temperature increase rate of 10 °C·min⻹ and a volume flow rate of 60 mL·min⻹, respectively. The results showed that due to the different polarity of the extraction solvent, the type and quantity of the chemical components contained in each polar part were different, and with the increase in the amount of solid powder of licorice, the peak of the maximum heat loss rate occurred in advance. For petroleum ether, chloroform, and ethyl acetate fractions, (157.40±1.06), 3.50, (25.83±1.66) °C in advance respectively, but the weight loss rate of the chloroform fraction was increased by (2.62±5.19) °C, while decreased by (33.90±1.72), (19.28±1.11) °C for the petroleum ether and ethyl acetate fractions. So we can conclude that with the addition of licorice, the pyrolysis rate of the petroleum ether and chloroform fractions in the toxic part of Kansui Radix was increased; the temperature point at the peak of the maximum weight loss rate was decreased, and the ethyl acetate fraction (effective part) showed a decrease in temperature rising process, but its overall ratio of weight loss and weight loss rate were relatively small, retaining the effect of medicinal ingredients. This proved the mechanism of licorice system Kansui Radix on attenuating toxicity after processing and the scientificity and rationality of licorice system Kansui Radix. At the same time, as the proportion of glycyrrhizin was increased, the peak of the maximum heat loss rate of petroleum ether, chloroform and ethyl acetate fractions occurred in advance; the peak temperature was decreased, with easy pyrolysis. Among them, the thermogravimetric rate of the mixture of petroleum ether and chloroform fractions (10:1) was relatively large, with a low peak temperature, while ethyl acetate fraction showed opposite results. This conclusion has certain guiding significance for the ratio of gansui to licorice.
Assuntos
Medicamentos de Ervas Chinesas/química , Euphorbia/química , Glycyrrhiza/química , Extratos Vegetais/química , Tecnologia Farmacêutica , Raízes de Plantas/química , TemperaturaRESUMO
BACKGROUND: Biomedical named entity recognition(BNER) is a crucial initial step of information extraction in biomedical domain. The task is typically modeled as a sequence labeling problem. Various machine learning algorithms, such as Conditional Random Fields (CRFs), have been successfully used for this task. However, these state-of-the-art BNER systems largely depend on hand-crafted features. RESULTS: We present a recurrent neural network (RNN) framework based on word embeddings and character representation. On top of the neural network architecture, we use a CRF layer to jointly decode labels for the whole sentence. In our approach, contextual information from both directions and long-range dependencies in the sequence, which is useful for this task, can be well modeled by bidirectional variation and long short-term memory (LSTM) unit, respectively. Although our models use word embeddings and character embeddings as the only features, the bidirectional LSTM-RNN (BLSTM-RNN) model achieves state-of-the-art performance - 86.55% F1 on BioCreative II gene mention (GM) corpus and 73.79% F1 on JNLPBA 2004 corpus. CONCLUSIONS: Our neural network architecture can be successfully used for BNER without any manual feature engineering. Experimental results show that domain-specific pre-trained word embeddings and character-level representation can improve the performance of the LSTM-RNN models. On the GM corpus, we achieve comparable performance compared with other systems using complex hand-crafted features. Considering the JNLPBA corpus, our model achieves the best results, outperforming the previously top performing systems. The source code of our method is freely available under GPL at https://github.com/lvchen1989/BNER .
Assuntos
Pesquisa Biomédica/instrumentação , Redes Neurais de Computação , Algoritmos , Pesquisa Biomédica/métodos , Armazenamento e Recuperação da Informação , Aprendizado de MáquinaRESUMO
Importance: While the association between cross-sectional measures of social isolation and adverse health outcomes is well established, less is known about the association between changes in social isolation and health outcomes. Objective: To assess changes of social isolation and mortality, physical function, cognitive function, cardiovascular disease (CVD), and stroke. Design, Setting, and Participants: In a cohort design, social isolation changes in 4 years and subsequent risk of mortality and other outcomes were assessed using the 13â¯649 eligible Health and Retirement Study (HRS) respondents from the 2006 to 2020 waves. Data were analyzed from October 11, 2023, to April 26, 2024. Exposure: The main exposure was the change in social isolation measured by the Steptoe 5-item Social Isolation Index from the initial assessment to a second assessment conducted 4 years later. Participants were classified into decreased isolation, stable, or increased isolation groups, stratified by their baseline isolation status. Main Outcomes and Measures: The primary outcomes were mortality, self-reported dependencies in activities of daily living, Alzheimer disease and Alzheimer disease-related dementia, CVD, and stroke. Dementia, CVD, and stroke were assessed using HRS-linked Medicare records. Incidence rates (IRs) of each group were estimated and a Cox proportional hazards regression model was used, with inverse-probability treatment weighting to adjust for confounders. Results: Among 13â¯649 participants (mean [SD] age at baseline, 65.3 [9.5] years; 8011 [58.7%] women) isolated at baseline, those with increased isolation had higher mortality (n = 693; IR = 68.19; 95% CI, 60.89-76.36 per 1000 person-years) than those who were stable (n = 1796; IR = 44.02; 95% CI, 40.47-47.88 person-years) or had decreased isolation (n = 2067; IR = 37.77; 95% CI, 34.73-41.09 person-years) isolation. Increased isolation was associated with higher risks of mortality (adjusted hazard ratio [AHR], 1.29; 95% CI, 1.09-1.51), disability (AHR, 1.35; 95% CI, 1.09-1.67), and dementia (AHR, 1.40; 95% CI, 1.02-1.93) compared with stable isolation. Similar findings were observed among socially nonisolated participants at baseline. Conclusions and Relevance: In this cohort study, increased isolation was associated with elevated risks of mortality, disability, and dementia, irrespective of baseline isolation status. These results underscore the importance of interventions targeting the prevention of increased isolation among older adults to mitigate its adverse effects on mortality, as well as physical and cognitive function decline.
Assuntos
Isolamento Social , Humanos , Feminino , Idoso , Isolamento Social/psicologia , Masculino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso de 80 Anos ou mais , Estados Unidos/epidemiologia , Estudos de Coortes , Demência/epidemiologia , Demência/mortalidade , Atividades Cotidianas , MortalidadeRESUMO
Water pollution induced by antibiotics has garnered considerable concern, necessitating urgent and effective removal methods. This study focused on exploring ciprofloxacin (CIP) removal by duckweed and assessing CIP bioaccumulation and toxic effects within duckweed under varying dissolved organic matter categories, pH levels, and nutrient (nitrogen (N) and phosphorus (P)) levels. The results revealed the proficient and rapid elimination of CIP from water by duckweed, resulting in 86.17 % to 92.82 % removal efficiency at the end of the 7-day experiment. Across all exposure groups, varying degrees of CIP bioaccumulation in duckweed were evident, with uptake established as a primary pathway for CIP elimination within this plant. Additionally, five CIP metabolites were identified in duckweed tissues. Interestingly, the presence of humic acid (HA) and fulvic acid (FA) reduced CIP absorption by duckweed, with FA yielding a more pronounced impact. Optimal CIP removal was recorded at a pH of 7.5, while duckweed displayed heightened physiological stress induced by CIP at pH 8.5. Although the influence of N and P concentrations on CIP removal by duckweed was modest, excessive N and P levels intensified the physiological strain of CIP on duckweed.
Assuntos
Araceae , Poluentes Químicos da Água , Ciprofloxacina/toxicidade , Ciprofloxacina/análise , Matéria Orgânica Dissolvida , Bioacumulação , Poluentes Químicos da Água/toxicidade , Antibacterianos/toxicidade , Nutrientes , Araceae/metabolismo , Concentração de Íons de HidrogênioRESUMO
Mastitis is an easy clinical disease in dairy cows, which seriously affects the milk yield and quality of dairy cows. Chlorogenic acid (CGA), a polyphenolic substance, is abundant in Eucommia ulmoides leaves and has anti-inflammatory and anti-oxidative stress effects. Here, we explore whether CGA attenuated lipopolysaccharide (LPS)-induced inflammation and decreased milk fat in bovine mammary epithelial cells (BMECs). 10 µg/mL LPS was used to induce mastitis in BMECs. QRT-PCR, Western blotting, oil red O staining, and triglyceride (TG) assay were used to examine the effects of CGA on BMECs, including inflammatory response, oxidative stress response, and milk fat synthesis. The results showed that CGA repaired LPS-induced inflammation in BMECs. The expression of IL-6, IL-8, TNF-α, IL-1ß, and iNOS was decreased, and the expression levels of CHOP, XCT, NRF2, and HO-1 were increased, which reduced the oxidative stress level of cells and alleviated the reduction of milk fat synthesis. In addition, the regulation of P65 phosphorylation by CGA suggests that CGA may exert its anti-inflammatory and anti-oxidative effects through the NF-κB signaling pathway. Our study showed that CGA attenuated LPS-induced inflammation and oxidative stress, and restored the decrease in milk fat content in BMECs by regulating the NF-κB signaling pathway.
RESUMO
Milk fat content is a critical indicator of milk quality. Exploring the key regulatory genes involved in milk fat synthesis is essential for enhancing milk fat content. STF-62247 (STF), a thiazolamide compound, has the potential to bind with ALG5 and upregulate lipid droplets in fat synthesis. However, the effect of STF on the process of milk fat synthesis and whether it acts through ALG5 remains unknown. In this study, the impact of ALG5 on milk fat synthesis and its underlying mechanism were investigated using bovine mammary epithelial cells (BMECs) and mouse models through real-time PCR, western blotting, Oil Red O staining, and triglyceride analysis. Experimental findings revealed a positive correlation between STF and ALG5 with the ability to synthesize milk fat. Silencing ALG5 led to decreased expression of FASN, SREBP1, and PPARγ in BMECs, as well as reduced phosphorylation levels in the PI3K/AKT/mTOR signaling pathway. Moreover, the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway were restored when ALG5 silencing was followed by the addition of STF. These results suggest that STF regulates fatty acid synthesis in BMECs by affecting the PI3K/AKT/mTOR signaling pathway through ALG5. ALG5 is possibly a new factor in milk fat synthesis.