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1.
Ecotoxicol Environ Saf ; 187: 109824, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654863

RESUMO

Microcystin-LR (MC-LR), a widespread environmental contaminant, has been shown to have potent acute testicular toxicity. However, magnitudes of toxic effects, induced by MCs, depend on route and magnitude of exposure to the toxin. In the present study, male mice were orally exposed 1, 10 or 100 µg/L MC-LR for 90 or 180 days, and pathological approach and the isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed with testes. Proteomics revealed that a number of differentially altered proteins may be involved in MC-LR-induced chronic testicular toxicity. The biological process analysis indicated the altered proteins played an important role in biological adhesion, cellular process, response to stimulus or rhythmic process. The cellular component analysis revealed that most of the proteins with altered expression associated with cell part, extracellular region, extracellular region part, membrane, membrane part, organelle or organelle part. The molecular function showed that these proteins were critical in molecular transducer activity. Integrity analyses provide first compelling evidence that MC-LR significantly cause dysfunction of blood-testis barrier (BTB) through affecting tight junctions and gap junctions. Moreover, phosphatidylinositol 3-kinase (PI3K)/AKT eventually contributed to injury result from chronic low-level MC-LR treatment. Identification of proteins in testis responsive to MC-LR provides insights into molecular mechanisms of chronic toxicity of MCs.

2.
Cytokine ; 125: 154820, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493564

RESUMO

BACKGROUND: The association of the IL-10 gene polymorphism with immune thrombocytopenic purpura (ITP, also called idiopathic thrombocytopenic purpura) susceptibility has been investigated in several studies; however, the association remains controversial. The present meta-analysis aimed to determine whether the IL-10 (-1082) polymorphism is associated with an increased risk of ITP. MATERIALS AND METHODS: Eligible articles were searched in EMBASE, PubMed, CNKI, WanFang, and HuGE Navigator, without any restriction of publication language. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to identify any potential associations between the IL-10 (-1082 A/G) polymorphism and the risk of ITP. RESULTS: This meta-analysis included six eligible studies with 384 cases and 409 controls. There was no significant association between the IL-10 (-1082) polymorphism and the risk of ITP in any of the genetic models. Three subgroups were stratified according to population ethnicity, disease subtype (acute or chronic), and age (child or adult). No statistically significant differences were observed in age and ethnicity between cases and controls. However, subtype analysis indicated significant associations for acute ITP in the allele model (OR = 1.76, 95% CI = [1.07; 2,89]), the recessive model (OR = 2.66, 95% CI = [1.17; 6.07]), and the homozygote model (OR = 2.65, 95% CI = [1.07; 6.55]). CONCLUSIONS: There is scarce evidence to confirm an association between the IL-10 (-1082) polymorphism and the risk of ITP. However, the IL-10 (-1082) polymorphism might be associated with the risk of acute ITP. Additional large, well-designed epidemiological studies should be performed to draw definitive conclusions.

3.
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.

4.
J Chem Inf Model ; 2019 Nov 15.
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 determining which one is the most favorable is a key step in molecular docking for SBVS due to the ligand induce-fit effect. This work aimed to find the most desirable crystal structures for molecular docking by a comprehensive analysis of the 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 the 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 relationships. This work provides great convenience for researchers to directly select the optimal crystal structure in SBVS-based kinase drug design and further validates the effectiveness of molecular docking in drug discovery.

5.
J Chromatogr A ; : 460651, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31753482

RESUMO

Most of the reported covalent organic frameworks (COFs) are hydrophobic, limiting their adsorption application in sample pretreatment field. In this work, sulphonate functionalized magnetic covalent organic frameworks (COFs) composites were first synthesized by loading gold nanoparticles on Fe3O4@COF(TpBD) surface and then functionalized by sodium 3-mercaptopropanesulphonate immobilization via Au-S bonding formation (denoted as Fe3O4@COF(TpBD)@Au-MPS nanocomposites), which were further utilized as adsorbents for magnetic solid-phase extraction (MSPE) of fluoroquinolones. Compared with Fe3O4@COF(TpBD), the composites exhibited higher affinity to fluoroquinolones. Under optimized conditions, the developed MSPE method coupled with HPLC-MS/MS showed good linearity (R2 ≥0.9989) and yielded low limits of detection (0.1-1.0 µg kg-1) for fluoroquinolones. Moreover, the proposed method was successfully applied to extract fluoroquinolones from spiked meats (pork, chicken and bovine). The satisfactory recoveries were in the range of 82-110.2% with the relative standard deviations (RSDs) lower than 7.7%. These results indicated that the Fe3O4@COF(TpBD)@Au-MPS is a promising magnetic adsorbent for trace fluoroquinolones determination in meat samples. This work not only provided a facile strategy for COF functionalization, but also developed an efficient method for detecting fluoroquinolones in foodstuffs.

6.
Int J Biol Macromol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739015

RESUMO

L. japonica has been used as food and healthy beverage due to the good nutrition. Although the chemical compounds have been extensively studied, polysaccharide compositions remain unclear. In this study, water-soluble polysaccharides of L. japonica were fractionated into one neutral fraction (LJP-N) and four acidic fractions (LJP-A-1 ~ LJP-A-4) by a combination of ion-exchange and gel permeation chromatographies. The structures and antioxidant activities of these factions were determined by HPLC, FT-IR and the radical scavenging activities, anti-hemolysis inhibitory ability, protective effect against DNA damage. Results showed that LJP-N was a starch-like glucan with some arabinogalactan; acidic fractions were all pectic polysaccharide, with the average molecular weights approximately ranging from 19.0 to 383.8 kDa. LJP-A-2 ~ LJP-A-4 were similar to each other, mainly composed of GalA (>50%) with some Gal and Ara residues, while LJP-A-1 mainly composed of Gal and Ara (>70%). LJP-A-3 was defined as HG-type pectic polysacchride, with a trace of RG-I domain by NMR experiment. The antioxidant activity of LJP fractions showed different activities, and LJP-A-3 and LJP-A-4 exhibited noticeable antioxidant activities by six kinds of evaluated methods comparable with others. The results indicated that LJP-A-3 and LJP-A-4 could be used as a potential natural source of antioxidant.

7.
Pharmacol Res ; : 104559, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759089

RESUMO

Our previous studies indicated that the G-protein-coupled bile acid receptor, Gpbar1 (TGR5), inhibits inflammation by inhibiting the NF-κB signalling pathway, eventually attenuating diabetic nephropathy (DN). Gentiopicroside (GPS), the main active secoiridoid glycoside of Gentiana manshurica Kitagawa, has been demonstrated to inhibit inflammation in various diseases via inhibiting the inflammatory signalling pathways. However, whether GPS inhibits the NF-κB signalling pathway by activating TGR5 and regulates the pathological progression of diabetic renal fibrosis requires further investigation. In this study, we found that GPS significantly reversed the downregulation of TGR5 and inhibited the overproduction of fibronectin (FN), transforming growth factor ß1 (TGF-ß1), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in glomerular mesangial cells (GMCs) exposed to high glucose (HG). Additionally, GPS prevented the phosphorylation and degradation of IκBα, and subsequently inhibited the activation of the NF-κB signalling pathway. Further investigation found that GPS enhanced the stabilization of IκBα by promoting the interaction of ß-arrestin2 with IκBα via TGR5 activation, which contributed to the inhibition of NF-κB signalling pathway. Importantly, the depletion of TGR5 blocked the inhibition of the NF-κB signalling pathway and reversed the downregulation of FN, ICAM-1, VCAM-1 and TGF-ß1 by GPS in HG-induced GMCs. Moreover, GPS increased the TGR5 protein levels and promoted the interaction between IκBα and ß-arrestin2, thereby inhibiting the reduction of IκBα and blocked NF-κB p65 nuclear translocation in the kidneys of STZ-induced diabetic mice. Collectively, these data suggested that GPS regulates the TGR5-ß-arrestin2-NF-κB signalling pathway to prevent inflammation in the kidneys of diabetic mice, and ultimately ameliorates the pathological progression of diabetic renal fibrosis.

8.
BMC Genomics ; 20(1): 851, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31726970

RESUMO

BACKGROUND: Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. RESULT: The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons. The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype ß2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. CONCLUSION: Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.

9.
Med Sci Monit ; 25: 8618-8627, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730575

RESUMO

BACKGROUND Worldwide, hepatocellular carcinoma (HCC) accounts for 80-90% of all cases of primary liver cancer, and is one of the ten most common malignancies. This study used bioinformatics analysis to identify genes associated with patient outcome in stages I-IV HCC and the gene pathways that distinguished between normal liver and liver cells and HCC and human HCC cell lines. MATERIAL AND METHODS Target genes were defined as those that had marketed drugs or drugs under development targeting a specific gene and acquired from the Clarivate Analytics Integrity Database. Differential expression gene analysis, co-expression network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, survival analysis and receiver operating characteristic (ROC) curve analysis were used to explore the similarities and differences in gene expression profiles, functional associations, and survival in stage I-IV HCC. Normal liver cells (HL-7702) and HCC cell lines (HepaRG, HepG2, SK-Hep1, and Huh7) were studied using Western blot and quantitative reverse transcription PCR (RT-qPCR). RESULTS Hierarchical gene clustering identified target genes that distinguished between HCC and normal liver tissue. For stages I-IV HCC, there were seven commonly upregulated target genes EPHB1, LTK, NTRK2, PTK7, TBK1, TIE1, and TLR3, which were mainly involved in immune and signaling transduction pathways. PTK7 was highly expressed in stage I-IV HCC and was an independent prognostic marker for reduced overall survival (OS). CONCLUSIONS Bioinformatics analysis, combined with patient survival analysis, identified PTK7 gene expression as a potential therapeutic target and prognostic biomarker for all stages of HCC.

10.
Mikrochim Acta ; 186(12): 823, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754804

RESUMO

A fluorometric assay is described for the determination of Cd(II) in environmental and agricultural samples. It is making use of a molecularly imprinted polymer (MIP) and aptamer as dual recognition units, while carbon quantum dots (co-doped with sulphur and nitrogen) and gold nanoparticles (SN-CQD/Au) act as the fluorophores. The aptamer-modified MIP was placed on an SN-CQD/Au-modified indium tin oxide glass electrode. Cd(II) was detected with high selectivity by the recognition sites of the aptamer in the MIP. Fluorescence, with excitation/emission peaks at 370/430 nm, is quenched by Cd(II). Response is linear in the 20 pM to 12 nM concentration range. The detection limit is 1.2 pM. The sensor is selective for Cd(II), and recoveries from spiked waters, soils and vegetables real-world samples range between 82.1 and 113.9%. Graphical abstractA fluorescence sensor composed of a molecularly imprinted polymer and an aptamer as a dual identification system for Cd2+ coupled with and carbon quantum dots (co-doped with sulphur and nitrogen) and gold nanoparticles (SN-CQDs/Au) as fluorescent element that can detect Cd2+ with high selectivity by a dual-recognition mechanism.

11.
Int J Pharm ; : 118894, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31765784

RESUMO

Uveal melanoma (UM) is rare yet the most common and malignant primary intraocular tumor in adults. Due to the lack of effective treatment, the mortality rate of UM has remained high over the past few decades. In the present study, hyaluronic acid (HA) coated chitosan (Chi)/siRNA ternary complexes have been developed and characterized as a novel therapeutic strategy molecularly targeting hypoxia-inducible factor 1α (HIF-1α) pathway for the treatment of UM. The cytotoxicity, cellular uptake, and siRNA silencing effect of the developed siRNA complexes were evaluated. In addition, whether the developed ternary complexes can inhibit UM migration and invasion was investigated. Results showed that the developed ternary siRNA complexes were negatively charged and with a particle size below 190 nm. The ternary siRNA complexes showed excellent cellular uptake and lysosome escape ability with low cytotoxicity. In addition, the ternary complexes were able to downregulate both HIF-1α and VEGF expression in UM cells, and successfully inhibit UM migration and invasion. These results demonstrated that the biocompatible ternary siRNA complexes are promising for local treatment of UM in the posterior segment with future clinical application potential.

12.
Sci China Life Sci ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31745693

RESUMO

Rapid weight gain (RWG) in infants is associated with numerous health problems, and its risk factors are still unclear. We assessed 98,097 maternal-infant pairs from a population-based cohort study and followed up with them until the infants were 6 months old. We assessed the associations between maternal prepregnancy weight status; gestational weight gain; feeding pattern; and infants' RWG at 0-1, 0-3, 1-3, and 3-6 months using multivariate unconditional logistic regression models, with controlled confounders. We found that maternal prepregnancy weight status, gestational weight gain, and feeding pattern at the 1st, 3rd, and 6th months had significant impacts on the infants' RWG at each time period (P<0.05). Infants with overweight/obese mothers had a higher risk of RWG after birth, whereas those of mothers who experienced excessive gestational weight gain had higher risks of RWG from birth than the other groups (P<0.01). Infants who were formula-fed had a higher risk of RWG than breastfed infants at the same time point (P<0.01). In conclusion, maternal prepregnancy obesity, excessive gestational weight gain, and formula-feeding were risk factors for infants' RWG during the first 6 months of life.

14.
Life Sci ; 239: 116881, 2019 Oct 31.
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.

15.
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.

16.
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.

17.
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.

18.
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.

19.
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.


Assuntos
Antígenos HLA/genética , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Implantação , Talassemia beta/diagnóstico , Variações do Número de Cópias de DNA , Feminino , Fertilização In Vitro , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Gravidez , Talassemia beta/genética
20.
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.

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