Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.873
Filtrar
1.
Appl Opt ; 58(27): 7517-7522, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674403

RESUMO

We designed an intensity modulation direct detection free-space laser communication terminal. In this system, the output power of the signal-modulated semiconductor laser amplified by two-stage fiber amplifier is 2 W, and the modulation contrast is 15 dB. Tracking of the incident beam and demodulation of the communication signal are realized by using a quadrant avalanche photodiode (APD). By means of rotating double Risley prisms, the ranges of the pitching angle and azimuth angle are ±35 and ±180 deg, respectively. The focal length of the transceiver lens is 125 mm, and the final communication field of view is 4 mrad. Without error correction coding, the sensitivity of -44.5 dBm was achieved, while the bit-error rate was below 10-3 at 70 Mbps. We also established a laser communication experiment at the laboratory; the platform jitter below 5 Hz can be effectively suppressed. The laser communication system has a compact structure, low power consumption, and effective suppression of low-frequency and high-amplitude angle jitter of the platform. The experiments demonstrate that the laser communication terminal can be used in an inter-satellite laser communication with a distance of thousands of kilometers. The theoretical analysis and experimental results are presented in the paper.

2.
Life Sci ; : 116881, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31678285

RESUMO

AIM: To investigate anti-liver fibrosis effects of Salvianolic acid B (Sal B) from Salvia miltiorrhiza Bunge involved mitogen-activated protein kinase (MAPK)-mediated transforming growth factor-beta (TGF-ß) signaling. MAIN METHODS: Diethylnitrosamine (DEN)-induced liver fibrosis in mice and TGF-ß1-activated hepatic stellate cells (HSCs) were established and treated with dosage/concentration-graded Sal B and/or MAPK activator (Vacquinol-1: MKK4-specific activator)/inhibitors (PD98059: ERK-specific inhibitor; SP600125: JNK-specific inhibitor; SB203580: p38-specific inhibitor). Histopathological characteristics and cell migration were assessed, α-SMA, Collagen I and members of TGF-ß/MAPK/Smad signal transduction pathway were measured. KEY FINDINGS: Results in vivo showed that Sal B alleviated DEN-caused liver fibrosis embodied in ameliorative histopathological characteristics and decreased protein levels of hepatic fibrosis related markers (α-SMA, Collagen I, TGF-ß1), its molecular mechanisms of action were correlative with inhibited activation of MAPK and phosphorylation of Smad2/3 at linker regions (P-Smad2/3L) and Smad2 at C-terminal (P-Smad2C) while increased phosphorylation of Smad3 at C-terminal (P-Smad3C). Results in vitro showed that Sal B restrained TGF-ß1-induced HSCs activation, Collagen I production and cell migration; Sal B inhibited activation of MAPK and markedly decreased protein levels of P-Smad2/3L and P-Smad2C while slightly increased P-Smad3C in TGF-ß1-stimulated HSCs, the expression of PAI-1 was inhibited by Sal B; activating MAPK receded inhibitory effects of Sal B on α-SMA, Collagen I, P-Smad2L and P-Smad3L expression while inhibited activation of MAPK reinforced those. SIGNIFICANCE: Sal B attenuates liver fibrosis via mediation of TGF-ß/Smad and MAPK pathways, especially inhibition of MAPK-mediated P-Smad2/3L signaling, which maybe provides theoretical foundation of Sal B for treating clinically liver fibrosis.

3.
Int J Med Mushrooms ; 21(6): 595-610, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679231

RESUMO

Antrodin C was obtained from Taiwanofungus camphoratus mycelia. The inhibition effect of antrodin C on A549 lung adenocarcinoma cells was evaluated by plate clone formation, wound healing, cell cycle, activated caspase-3, Bax, P53, Bcl-2, and RAPR activities as well as reactive oxygen species release. Plate clone formation assay revealed that antrodin C could significantly inhibit the viability of A549 cells in vitro. Wound healing assay revealed that cell migration was inhibited by exposure to antrodin C at concentrations of 50 and 80 µg/mL. Flow cytometry revealed that antrodin C increased the percentages of cells in the G0/G1 phase at concentrations of 50 and 80 µg/mL and the apoptosis was related to upregulation of caspase-3, Bax, P53 expression, downregulation of Bcl-2, RAPR expression, and the release of reactive oxygen species in the A549 cells. CQ or RAPA could significantly promote or inhibit the inhibition effect on A549 proliferation induced by antrodin C, which suggests that the autophagy played a cytoprotective role on inhibition proliferation of A549 induced by antrodin C. These results indicated that the combination of pro-apoptosis agents and anti-autophagy agents may be a useful strategy in enhancing the anticancer efficacy in non-small cell lung cancer.

4.
Opt Express ; 27(20): 27927-27935, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684553

RESUMO

Since the electromagnetic resonance that happens in dielectric nanobricks can be meticulously designed to control both amplitude and polarization of light, an ultracompact, high-resolution and continuous grayscale image display method based on resonant dielectric metasurfaces is proposed. Magnetic resonance occurs in dielectric nanobricks can yield unusual high reflectivity depending on the polarization state of incident light, which paves a new way for ultracompact image display when the resonant metasurfaces consisting of nano-polarizer arrays operate. Governed by Malus's law, nano-polarizer arrays featured with different orientations have been demonstrated to continuously manipulate the intensity of linearly polarized light cell-by-cell. Hence, it can practically enable recording a high fidelity grayscale image right at the sample surface with resolution as high as 84,667 dpi (dots per inch). This proposed resonant metasurface image (meta-image) display enjoys the advantages including continuous grayscale modulation, broadband working window, high-stability and high-density, which can easily find promising applications in ultracompact displays, high-end anti-counterfeiting, high-density optical information storage and information encryption, etc.

5.
Environ Res ; 180: 108825, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31683121

RESUMO

Chemical contamination in the environment is known to cause abnormal circular RNA (circRNA) expression through multiple exposure routes; yet, the underlying molecular mechanisms remain unclear. Non-coding RNAs (ncRNAs), especially circRNAs, play important roles in epigenetic regulation and disease pathogenesis; however, few studies have examined the function of circRNAs in chemical contamination-induced diseases. CircRNAs are covalently closed continuous loops that do not possess 5' and 3' ends, increasing their structural stability and limiting degradation by exoribonucleases. In addition, environmental chemical exposure-related diseases are often accompanied by aberrant expression of specific circRNAs and those circRNAs are often detected in tissues and body fluids. Based on these characteristics, circRNAs may serve as candidate biomarkers for the diagnosis of diseases related to environmental chemical exposure. Here, we review the generation and function of circRNAs, and the possible molecular mechanisms underlying the regulation of environmental chemical exposure-related disorders by circRNAs. This is the first comprehensive review of the relationship between environmental chemical exposure and circRNAs in chemical exposure-induced diseases.

6.
J Chem Inf Model ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31689093

RESUMO

Protein kinases are important drug targets in several therapeutic areas and structure-based virtual screening (SBVS) is an important strategy in discovering lead compounds for kinase targets. However, there are multiple crystal structures available for each target and to determine which one is the most favorable is a key step in molecular docking for SBVS due to ligand induce-fit effect. This work aimed to find the most desirable crystal structures for molecular docking by a comprehensive analysis of protein kinase database which covers 190 different kinases from all eight main kinase families. Through an integrated self-docking and cross-docking evaluation, 86 targets were eventually evaluated on a total of 2608 crystal structures. Results showed that molecular docking has great capability in reproducing conformation of crystallized ligands and for each target, the most favorable crystal structure was selected, and AGC family outperformed the other family targets based on RMSD comparison. In addition, RMSD values, GlideScore and corresponding bioactivity data were compared and demonstrated certain relationship. This work provides great convenience for researchers to directly select the optimal crystal structure in SBVS-based kinase drug design, and further validate the effectiveness of molecular docking in drug discovery.

7.
J Anat ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670395

RESUMO

Since embryonic heart development is a complex process and acquisition of human embryonic specimens is challenging, the mechanism by which the embryonic conduction system develops remains unclear. Herein, we attempt to gain insights into this developmental process through immunohistochemical staining and 3D reconstructions. Expression analysis of T-box transcription factor 3, cytoskeleton desmin, and nucleoskeleton lamin A protein in human embryos in Carnegie stages 11-20 showed that desmin is preferentially expressed in the myocardium of the central conduction system compared with the peripheral conduction system, and is co-expressed with T-box transcription factor 3 in the central conduction system. Further, lamin A was first expressed in the embryonic ventricular trabeculations, where the terminal ramifications of the peripheral conduction system develop, and extended progressively to all parts of the central conduction system. The uncoupled spatiotemporal distribution pattern of lamin A and desmin indicated that the association of cytoskeleton desmin and nucleoskeleton lamin A may be a late event in human embryonic heart development. Compared with model animals, our data provide a direct morphological basis for understanding the arrhythmogenesis caused by mutations in human DES and LMNA genes.

8.
Plant Cell Physiol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670803

RESUMO

Pentatricopeptide repeat (PPR) proteins are helical repeat RNA binding proteins that function in RNA processing by conferring sequence-specific RNA binding activity. Owing to lethality of PPR mutants, functions of many PPR proteins remain obscure. Here, we report the function of PPR20 in intron splicing in mitochondria and its role in maize seed development. PPR20 is a P-type PPR protein targeted to mitochondria. The ppr20 mutants display slow embryo and endosperm development. Null mutation of PPR20 severely reduces the cis-splicing of mitochondrial nad2 intron 3, resulting in reduction in the assembly and activity of mitochondrial complex I. The ppr20-35 allele with a Mu insertion in the N-terminal region shows a much weaker phenotype. Molecular analyses revealed that the mutant produces a truncated transcript, coding for PPR20ΔN120 lacking the N-terminal 120 amino acids. Subcellular localization revealed that PPR20ΔN120: GFP is able to target to mitochondria as well, suggesting the sequence diversity of the mitochondrial targeting peptides. Another mutant zm_mterf15 was also found to be impaired in the splicing of mitochondrial nad2 intron 3. Further analyses are required to identify the exact function of PPR20 and Zm_mTERF15 in the splicing of nad2 intron 3.

9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 714-718, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699206

RESUMO

Leucine-rich glioma-inactivated protein 1(LGI1)antibody-associated encephalitis is an autoimmune brain disease mainly seen in mid-aged and elderly people.Its main clinical manifestations include abnormal mental behaviors,facial-arm dystonia,hyponatremia,and hypokalemia.Immunotherapy with gamma globulin and/or hormone is effective.Two patients with LGT1 antibody-associated encephalitis were diagnosed in our center between January 2018 and October 2018,with typical clinical findings.The disease was cursed after immunoglobulin and hormone treatments.

10.
Sci Rep ; 9(1): 16172, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700086

RESUMO

Phellinus baumii, also called "Sang Huang" in China, is broadly used as a kind of health food or folk medicine in Asia for its high biological activities, e.g. anti-tumor, anti-oxidation and anti-inflammatory activities. Although some previous studies have indicated that polysaccharides and flavonoids showed the activity of inhibiting tumor cells, the active metabolites of P. baumii needs further research. In our study, a stable P. baumii mutant (A67), generated by ARTP mutagenesis strategy, showed more significantly inhibiting tumor cells and enhancing antioxidant activity. Our further studies found that the increase of polyphenols content, especially hispidin, was an important reason of the biological activity enhancement of A67. According to the results of the integrated metabolome and proteome study, the increase of polyphenol content was caused by upregulation of the phenylpropanoid biosynthesis. This study expanded the understanding of active compounds and metabolic pathway of P. baumii.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1090-1093, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703132

RESUMO

OBJECTIVE: To assess the value of next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping for preimplantation genetic diagnosis (PGD) for beta-thalassemia coupled with human leukocyte antigen (HLA) matching. METHODS: Three couples were recruited. Couple 1 both carried a ß (IVS-2-654) variation and had previously given birth to a son with ß thalassemia major. Couple 2 respectively carried (cd41-42) and ß (IVS-2-654) but had no history of pregnancy. Couple 3 respectively carried ß (CD17) and ß (IVS-2-654), and had a daughter carrying ß (CD17). RESULTS: For couple 1, NGS-SNP typing identified two embryos not only unaffected with thalassemia but also with matched HLA. One blastocyst was transferred and resulted in successful pregnancy. A healthy baby was born at 39th week of gestation. Its umbilical blood was used to treat the sick brother through hemopoietic stem cell transplantation. For couple 2, seven blastocysts were obtained. Second transplantation has resulted in successful pregnancy. Prenatal diagnosis was consistent with PGD. For couple 3, two blastocysts not only unaffected with thalassemia but also with no pathogenic copy number variations were obtained. Transfer of one blastocyte resulted in successful pregnancy, and prenatal diagnosis was consistent with PGD. CONCLUSION: NGS-based SNP typing is an useful tool for selecting embryos unaffected with beta-thalassemia and matched HLA through PGD.

12.
Pathol Oncol Res ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606786

RESUMO

Tumor-infiltrating immune cells engage in an extensive crosstalk with tumors and act as two-edged swords by inhibiting or promoting cancer growth. Therefore, identifying the density and prognostic values of tumor-infiltrating immune cells will provide valuable tips for cancer treatments. In this study, we identified the density of tumor inflammatory infiltrates and the number of tumor-infiltrating immune cells, including CD3+, CD4+, CD8+, FoxP3+ T cells and CD1a+ dendritic cells (DCs) in 153 tongue squamous cell carcinomas (TSCC). High inflammatory cell infiltration was associated with better overall survival (OS) and disease free survival (DFS). Moreover, the number of CD3+, CD4+, FoxP3+ and CD1a+ cells were associated with tumor differentiation (P<0.001) and the number of FoxP3+, CD1a+ cells and CD8+/FoxP3+ ratios were also associated with tumor stage (P<0.01, P<0.01, P<0.05). In addition, patients with higher CD1a+ DCs had better OS and increased CD8+/FoxP3+ ratios were associated with improved OS and DFS (P = 0.037; P = 0.047; P = 0.033). In conclusion, our results indicated that tumor-infiltrating CD1a+ DCs and CD8+/FoxP3+ ratios were associated with favorable clinical outcomes but not independent prognostic factors for TSCC patients.

13.
Biosens Bioelectron ; 146: 111734, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586759

RESUMO

Highly-conductive two-dimensional covalent organic framework (COF) displays prominent applications in various fields of science and technology. This paper reports the design and liquid-liquid interface synthesis of a novel Zr-coordinated amide porphyrin-based 2D COF (Zr-amide-Por-based 2D COF). The COF adopts a graphene-like multilayer structure with the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) band gap of 1.6 eV. The ordered multilayer structure of the amide COF was confirmed through a series of characterization techniques, including scanning electron microscopy, high-resolution transmission electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. In particular, the inherent-ordered structure of Zr-amide-Por-based 2D COF with Zr as the catalytically active center confers several distinct advantages to the material, such as high conductivity and high electrocatalysis performance. A molecularly imprinted tetracycline electrochemiluminescence sensor was constructed based on the Zr-amide-Por-based 2D COF, and gate control effect was used as a signal-generation mechanism. Under optimal conditions, the sensor showed a good linear relationship with tetracycline in the concentration range of 5-60 pM, with a detection limit of 2.3 pM. Because the sensor is rapid, cost-efficient, highly sensitive, and specific, it can be considered as a viable platform for veterinary drug residue monitoring.

14.
BMC Genomics ; 20(1): 773, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651238

RESUMO

BACKGROUND: Plant homeodomain (PHD) finger proteins are widely present in all eukaryotes and play important roles in chromatin remodeling and transcriptional regulation. The PHD finger can specifically bind a number of histone modifications as an "epigenome reader", and mediate the activation or repression of underlying genes. Many PHD finger genes have been characterized in animals, but only few studies were conducted on plant PHD finger genes to this day. Brassica rapa (AA, 2n = 20) is an economically important vegetal, oilseed and fodder crop, and also a good model crop for functional and evolutionary studies of important gene families among Brassica species due to its close relationship to Arabidopsis thaliana. RESULTS: We identified a total of 145 putative PHD finger proteins containing 233 PHD domains from the current version of B. rapa genome database. Gene ontology analysis showed that 67.7% of them were predicted to be located in nucleus, and 91.3% were predicted to be involved in protein binding activity. Phylogenetic, gene structure, and additional domain analyses clustered them into different groups and subgroups, reflecting their diverse functional roles during plant growth and development. Chromosomal location analysis showed that they were unevenly distributed on the 10 B. rapa chromosomes. Expression analysis from RNA-Seq data showed that 55.7% of them were constitutively expressed in all the tested tissues or organs with relatively higher expression levels reflecting their important housekeeping roles in plant growth and development, while several other members were identified as preferentially expressed in specific tissues or organs. Expression analysis of a subset of 18 B. rapa PHD finger genes under drought and salt stresses showed that all these tested members were responsive to the two abiotic stress treatments. CONCLUSIONS: Our results reveal that the PHD finger genes play diverse roles in plant growth and development, and can serve as a source of candidate genes for genetic engineering and improvement of Brassica crops against abiotic stresses. This study provides valuable information and lays the foundation for further functional determination of PHD finger genes across the Brassica species.

15.
J Oral Pathol Med ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31660637

RESUMO

BACKGROUND: MLL2 (mixed-lineage leukemia 2) is recognized as an essential role in regulating histone 3 lysine 4 tri-methylation (H3K4me3) in mammalian cells. It is frequently mutated to promote developmental diseases and tumor initiation. However, the expression pattern of MLL2 and its clinical significance for patients with early-stage oral squamous cell carcinoma (OSCC) remains totally unknown. METHODS: 85 samples of primary early-stage OSCC were enrolled in this retrospective study and immunohistochemistry (IHC) was performed to detect the spatial pattern of MLL2. The diagnostic and prognostic value of MLL2 were assessed. RESULTS: MLL2 was widely expressed in tumor cells (TCs), fibroblast-like cells (FLCs) and tumor-infiltrating lymphocytes (TILs), both in tumor center and invasive tumor front, and showed no distributive heterogeneity. Moreover, regardless of cell types and microlocalization, patients with high expressed MLL2 had increased depth invasion of tumor (DOI). Besides, upregulation of MLL2TC and MLL2TIL in tumor center were both associated with poor differentiation, but showed no correlation with tumor growth with comparable Ki-67 levels. Prognostic analysis indicated that early-stage OSCC patients with enhanced MLL2TIL in invasive tumor front was susceptible to occur postoperative metastasis and recurrence. Indeed, patients with higher expressed MLL2TIL showed shorter overall survival (OS) and disease-free survival (DFS), and MLL2TIL in invasive tumor front was an independent risk factor of DFS. CONCLUSION: TIL-derived MLL2 in invasive tumor front was an independent prognostic factor of DFS for early-stage OSCC patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31665550

RESUMO

OBJECTIVE: To compare the value of the Thyroid Imaging Reporting and Data System proposed by Kwak (KWAK TI-RADS) and the 2015 American Thyroid Association (ATA) guidelines for diagnosis of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) and confirm the role of cell block (CB)-assisted fine-needle aspiration (FNA) in the final diagnosis of MTC. METHODS: Ninety-three patients with 29 MTCs, 31 PTCs, and 33 follicular adenomas (FAs) who underwent thyroidectomy from January 2010 to May 2019 were retrospectively reviewed. The KWAK TI-RADS and ATA guidelines were used to assess each thyroid nodule. FNA, CB-assisted FNA, and core needle biopsy (CNB) were performed for the final diagnosis. RESULTS: Age and ultrasound features (composition, echogenicity, and shape) were significantly different between MTC and PTC. Sex and ultrasound features (echogenicity, margin, and calcification) were significantly different between MTC and FA. The KWAK TI-RADS and ATA guidelines showed no significant difference for MTC [area under the curve (AUC): 0.812 and 0.808; P=0.37-0.85] or PTC (AUC: 0.883 and 0.885; P=0.25-0.96). The KWAK TI-RADS and ATA guidelines showed high specificity and sensitivity for MTC (93.9% and 62.1%, 87.9% and 65.5%) and PTC (93.9% and 67.7%, 87.9% and 77.4%). For suspicious MTC (7 cases), CB-assisted FNA provided an accurate preoperative diagnosis. CONCLUSIONS: Although the diagnostic performance of the TI-RADS and ATA guidelines is worse for MTC than PTC, the difference is not statistically significant. CB-assisted FNA should be performed in thyroid nodules with 4a or lower suspicion to avoid misdiagnosis of MTC.

17.
Molecules ; 24(20)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627460

RESUMO

The dried vine stems of Spatholobus suberectus are commonly used in traditional Chinese medicine for treating gynecological and cardiovascular diseases. In this study, five new compounds named spasuberol A (2), homovanillyl-4-oxo-nonanoate (5), spasuberol C (6), spasuberoside A (14), and spasuberoside B (15), together with ten known compounds (1, 3, 4, 7-13), were isolated from the dried vine stems of S. suberectus. Their chemical structures were analyzed using spectroscopic assays. This is the first study interpreting the detailed structural information of 4. The anti-inflammatory activity of these compounds was evaluated by reducing nitric oxide overproduction in RAW264.7 macrophages stimulated by lipopolysaccharide. Compounds 1 and 8-10 showed strong inhibitory activity with half maximal inhibitory concentration (IC50) values of 5.69, 16.34, 16.87, and 6.78 µM, respectively, exhibiting higher activity than the positive drug l-N6-(1-iminoethyl)-lysine (l-NIL) with an IC50 value of 19.08 µM. The IC50 values of inhibitory activity of compounds 2 and 4-6 were 46.26, 40.05, 45.87, and 28.29 µM respectively, which were lower than l-NIL, but better than that of positive drug indomethacin with an IC50 value of 55.44 µM. Quantitative real-time polymerase chain reaction analysis revealed that assayed compounds with good anti-inflammatory activity, such as 1, 6, 9, and 10 at different concentrations, can reduce the messenger RNA (mRNA) expression of some pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). The anti-inflammatory activity and the possible mechanism of the compounds mentioned in this paper were studied preliminarily.

18.
Mol Pharm ; 16(11): 4472-4484, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31580683

RESUMO

Machine intelligence has been greatly developed in the past decades and has been widely used in many fields. In the recent years, many reports have shown its satisfactory effect in drug discovery. In this study, machine intelligence methods were explored to assist the cell activity prediction. Multiple machine intelligence methods including support vector machine, decision tree, random forest, extra trees, gradient boosting machine, convolutional neural network, long short-term memory network, and gated recurrent unit network were employed to separate compounds based on their cell activity. Different from some reported classification models, compounds were expressed as a string by the simplified molecular input line entry system and directly used as input rather than any chemical descriptors, which mimicked natural language processing. Both the single cell strain and whole data set under the balanced and imbalanced data distributions were discussed, respectively. Different activity cutoffs were set for the single (Z-score = 3) and the whole (Z-score = 5 and 6) data set. Nine metrics were used to evaluate the models including accuracy, precision, recall, f1-score, area under the receiver operating characteristic curve score, Cohen's κ, Brier score, Matthews correlation coefficient, and balanced accuracy. The results show that the gradient boosting machine is competent at balanced data distribution, and convolutional neural network is qualified for the imbalanced one. The results demonstrate that both classic machine learning methods and deep learning methods have potential in classification of compound cell activity.

19.
Chin Med J (Engl) ; 132(20): 2457-2464, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31651510

RESUMO

OBJECTIVE: Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases. DATA SOURCES: The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science. STUDY SELECTION: The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type. RESULTS: CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5' and 3' ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases. CONCLUSIONS: Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient's body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.

20.
Endocrinology ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638695

RESUMO

Obesity and insulin resistance stiffen the vasculature with females appearing to be more adversely affected. As augmented arterial stiffness is an independent predictor of cardiovascular disease (CVD), the increased predisposition of obese and insulin-resistant women to arterial stiffening may explain their heightened risk for CVD. However, the cellular mechanisms by which females are more vulnerable to arterial stiffening associated with obesity and insulin resistance remain largely unknown. Here we provide evidence that female mice are more susceptible to Western diet-induced endothelial cell stiffening compared to age-matched males. Mechanistically, we show that the increased stiffening of the vascular intima in Western diet-fed female mice is accompanied by enhanced epithelial sodium channel (ENaC) activity in endothelial cells (EnNaC). Our data further indicate that: 1) estrogen signaling through estrogen receptor alpha (ERα) increases EnNaC activity to a larger extent in females compared to males, 2) estrogen-induced activation of EnNaC is mediated by the serum glucocorticoid inducible-kinase 1 (SGK-1), and 3) estrogen signaling stiffens endothelial cells when nitric oxide is lacking and this stiffening effect can be reduced with amiloride, an ENaC inhibitor. In aggregate, we demonstrate a sexual dimorphism in obesity-associated endothelial stiffening, whereby females are more vulnerable than males. In females, endothelial stiffening with obesity may be attributed to estrogen signaling through the ERα-SGK-1-EnNaC axis, thus establishing a putative therapeutic target for female obesity-related vascular stiffening.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA