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1.
Virus Res ; 275: 197804, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697988

RESUMO

Porcine circovirus 3 (PCV3) is a novel circovirus that is associated with porcine dermatitis and nephropathy syndrome, reproductive failure, and multi-systemic inflammation. The type I Interferon (IFN) signaling pathway is an important innate immune signaling pathway for defense against viral infection. Many mammalian viruses inhibit host innate immune signaling through diverse strategies. Here, we found that the PCV3 capsid protein (Cap) significantly inhibited IFN-ß-stimulated response element (ISRE) promoter activity, suggesting that Cap suppresses IFN signaling. However, Cap did not affect expression and phosphorylation levels of STAT1 and STAT2 and did not interrupt the heterodimerization of pSTAT1 and pSTAT2. Although Cap interacted with KPAN1, it did not block the interaction between KPNA1 and pSTAT1 or the nuclear translocation of pSTAT1 and pSTAT2. Interestingly, we found that Cap inhibited the activation of ISRE promoter induced by IRF9-S2C. Mechanistically, Cap interacted with the transactivation domain of STAT2, a key protein in type I IFN signaling. In addition, we found that Cap bound to ISRE and prevented ISRE binding of IRF9-S2C. This work is the first to describe the mechanism of inhibition of IFN signaling by PCV3 Cap.

2.
Opt Lett ; 44(22): 5406-5409, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730069

RESUMO

Intravascular photoacoustic (IVPA) imaging, benefiting from high optical contrast, large imaging depth and absorption specificity, is of great potential for lipid-rich plaque detection. However, the diameters of reported IVPA endoscopes are too big to intervene into the coronary artery branches. Here, by designing an ultracompact house embedded with a side-fire fiber and a miniature single-element ultrasound transducer, we developed an ultrafine IVPA endoscope with a diameter of 0.7 mm aiming at coronary artery branches atherosclerotic plaque detection. The reliability and feasibility of the ultrafine IVPA endoscope was demonstrated by imaging a stent with a 1.6 mm inner diameter. Furthermore, the photoacoustic imaging and ultrasound imaging of a mouse thoracic aorta with an inner diameter of 1.15 mm was conducted to verify the clinical potentiality of the endoscope, and the PA images have good consistency with histological staining results. To the best of our knowledge, this is the first time we have achieved the IVPA imaging in fine vessel by the 0.7 mm diameter ultrafine photoacoustic endoscope, which paved a way for the translation of the IVPA endoscope to clinical application.

3.
PLoS One ; 14(11): e0224677, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31703075

RESUMO

Chicken mitochondrial DNA is a circular molecule comprising ~16.8 kb. In this study, we used next-generation sequencing to investigate mitochondrial heteroplasmy in the whole chicken mitochondrial genome. Based on heteroplasmic detection thresholds at the 0.5% level, 178 cases of heteroplasmy were identified in the chicken mitochondrial genome, where 83% were due to nucleotide transitions. D-loop regionwas hot spot region for mtDNA heteroplasmy in the chicken since 130 cases of heteroplasmy were located in these regions. Heteroplasmy varied among intraindividual tissues with allele-specific, position-specific, and tissue-specific features. Skeletal muscle had the highest abundance of heteroplasmy. Cases of heteroplasmy at mt.G8682A and mt.G16121A were validated by PCR-restriction fragment length polymorphism analysis, which showed that both had low ratios of heteroplasmy occurrence in five natural breeds. Polymorphic sites were easy to distinguish. Based on NGS data for crureus tissues, mitochondrial mutation/heteroplasmy exhibited clear maternal inheritance features at the whole mitochondrial genomic level. Further investigations of the heterogeneity of the mt.A5694T and mt.T5718G transitions between generations using pyrosequencing based on pedigree information indicated that the degree of heteroplasmy and the occurrence ratio of heteroplasmy decreased greatly from the F0 to F1 generations in the mt.A5694T and mt.T5718G site. Thus, the intergenerational transmission of heteroplasmy in chicken mtDNA exhibited a rapid shift toward homoplasmy within a single generation. Our findings indicate that heteroplasmy is a widespread phenomenon in chicken mitochondrial genome, in which most sites exhibit low heteroplasmy and the allele frequency at heteroplasmic sites changes significantly during transmission events. It suggests that heteroplasmy may be under negative selection to some degree in the chicken.

4.
Ecotoxicol Environ Saf ; 188: 109908, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31706243

RESUMO

Pesticides have been extensively produced and used to help the agricultural production which leads to the contamination of the environment, soil, groundwater sources, and even foodstuffs. Fungicides carbendazim (CBZ) and chlorothalonil (Chl) are widely applied in agriculture and other aspects. CBZ or Chl have been reported to disrupt spermatogenesis and decrease semen quality. However, it is not understood the effects of pubertal exposure to low doses of CBZ and Chl together, and the underlying mechanisms. Therefore, the aim of current investigation was to explore the negative impacts of pubertal exposure to low doses of CBZ and Chl together on spermatogenesis and the role of epigenetic modifications in the process. We demonstrated that CBZ and Chl together synergize to decrease sperm motility in vitro (CBZ 1.0 + Chl 0.1, CBZ 10.0 + CHl 1.0, CBZ 100.0 + Chl 10 µM in incubation medium for 24 h) and sperm concentration and motility in vivo with ICR mice (CBZ 0.1 + Chl 0.1, CBZ 1.0 + CHl 1.0, CBZ 10.0 + Chl 10 mg/kg body weight; oral gavage for five weeks). CBZ + Chl significantly increase reactive oxygen species (ROS) and apoptosis by the increase in the protein level of caspase 8 in vitro. Moreover, CBZ + Chl synergized to disrupt mouse spermatogenesis with the disturbance in sperm production proteins and sperm proteins (VASA, A-Myb, STK31, AR, Acrosin). CBZ + Chl synergized to decrease the protein level of estrogen receptor alpha and the protein level of DNA methylation marker 5 mC in Leydig cells, and to increase the protein levels of histone methylation marker H3K9 and the methylation enzyme G9a in germ cells. Therefore, greater attention should be paid to the use of CBZ and Chl as pesticides to minimise their adverse impacts on spermatogenesis.

5.
J Exp Clin Cancer Res ; 38(1): 443, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31666112

RESUMO

In the original publication of this article [1], the author would like to revise Figure 4.

6.
Opt Express ; 27(22): 31225-31234, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684357

RESUMO

We present and experimentally demonstrate a novel oxide-confined ridge-waveguide distributed feedback (DFB) laser with the first-order surface grating using only a single growth step. The metal contacts are laterally offset from the ridge waveguide to inject current thus avoiding unwanted light absorption from the electrodes. The oxide aperture is defined by selective wet oxidation of aluminium-rich material, which confines the injection current from the electrodes to the active layer under the ridge waveguide. This allows that a thin ridge layer can be used with relatively higher refractive index compared to the active layer and thus the grating can be shallowly etched but provides a strong coupling effect. The fabricated 150 µm-long DFB laser exhibited a relatively low threshold current of 8 mA and a side mode suppression ratio (SMSR) up to 50 dB at the injected current of 32 mA around 4 times threshold at 20 °C. Stable single mode operation has been observed for the fabricated DFB laser over the temperature range from 10 to 50 °C. The variation of wavelength with temperature Δλ/ΔT was 0.06 nm/°C. The proposed laser may have advantages combined both DFB lasers and vertical-cavity surface-emitting lasers (VCSELs), such as single mode, stabilized polarization, potentially narrow linewidth and low power consumption. In addition, the laser is regrowth free, thus has advantages of low cost and high reliability.

7.
Sensors (Basel) ; 19(22)2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31744236

RESUMO

The Global Navigation Satellite System (GNSS) is currently one of the important tools for landslide monitoring and early warning. However, the majority of GNSS devices are installed in mountainous areas and a variety of vegetation. These harsh environments lead to defective signals at high elevation angles, rendering real-time successive and reliable positioning results for monitoring difficult. In this study, an environmental model derived from signal-to-noise ratio (SNR) is proposed to enhance the precision and convergence time of positioning in harsh environments. A series of experiments are conducted on weighting and ambiguity-fixed models to evaluate performance. The results indicate that the proposed SNR-dependent environment model could lead to a significant improvement in precision and convergence time; with an obtained root mean squared result on the millimeter level, a convergence time of a few seconds, and utilization which could reach 100%, for continuous and reliable positioning results. These results indicate that the proposed SNR-dependent environment model enhances the performance of GNSS monitoring and early warning to provide continuous and reliable positioning results in real-time.

8.
J Org Chem ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755261

RESUMO

The Diels-Alder (DA) reaction strategy that can rapidly extend the conjugated backbone was applied to facilely synthesize fold-line, coplanar BN-embedded polycyclic aromatic hydrocarbons (PAHs) from simple small BN compounds. The molecular structures and packing modes of these BN-embedded acenes were confirmed by single crystal X-ray diffraction. Their electronic and photophysical properties were studied by using UV-vis, fluorescence spectroscopy, electrochemical cyclic voltammetry, and density functional theory (DFT) calculation. These results demonstrate the efficiency and feasibility of this synthetic strategy.

9.
Exp Eye Res ; 190: 107865, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682846

RESUMO

Human CD34 + stem cells are mobilized from bone marrow to sites of tissue ischemia and play an important role in tissue revascularization. This study used a murine model to test the hypothesis that intravitreal injection of human CD34 + stem cells harvested from bone marrow (BMSCs) can have protective effects in eyes with diabetic retinopathy. Streptozotocin-induced diabetic mice (C57BL/6J) were used as a model for diabetic retinopathy. Subcutaneous implantation of Alzet pump, loaded with Tacrolimus and Rapamycin, 5 days prior to intravitreal injection provided continuous systemic immunosuppression for the study duration to avoid rejection of human cells. Human CD34 + BMSCs were harvested from the mononuclear cell fraction of bone marrow from a healthy donor using magnetic beads. The CD34 + cells were labeled with enhanced green fluorescent protein (EGFP) using a lentiviral vector. The right eye of each mouse received an intravitreal injection of 50,000 EGFP-labeled CD34 + BMSCs or phosphate buffered saline (PBS). Simultaneous multimodal in vivo retinal imaging system consisting of fluorescent scanning laser ophthalmoscopy (enabling fluorescein angiography), optical coherence tomography (OCT) and OCT angiography was used to confirm the development of diabetic retinopathy and study the in vivo migration of the EGFP-labeled CD34 + BMSCs in the vitreous and retina following intravitreal injection. After imaging, the mice were euthanized, and the eyes were removed for immunohistochemistry. In addition, microarray analysis of the retina and retinal flat mount analysis of retinal vasculature were performed. The development of retinal microvascular changes consistent with diabetic retinopathy was visualized using fluorescein angiography and OCT angiography between 5 and 6 months after induction of diabetes in all diabetic mice. These retinal microvascular changes include areas of capillary nonperfusion and late leakage of fluorescein dye. Multimodal in vivo imaging and immunohistochemistry identified EGFP-labeled cells in the superficial retina and along retinal vasculature at 1 and 4 weeks following intravitreal cell injection. Microarray analysis showed changes in expression of 162 murine retinal genes following intravitreal CD34 + BMSC injection when compared to PBS-injected control. The major molecular pathways affected by intravitreal CD34 + BMSC injection in the murine retina included pathways implicated in the pathogenesis of diabetic retinopathy including Toll-like receptor, MAP kinase, oxidative stress, cellular development, assembly and organization pathways. At 4 weeks following intravitreal injection, retinal flat mount analysis showed preservation of the retinal vasculature in eyes injected with CD34 + BMSCs when compared to PBS-injected control. The study findings support the hypothesis that intravitreal injection of human CD34 + BMSCs results in retinal homing and integration of these human cells with preservation of the retinal vasculature in murine eyes with diabetic retinopathy.

10.
Curr Top Med Chem ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31775591

RESUMO

The rapid development of nanotechnology has a great influence in the fields of biology, physiology, and medicine. Over recent years, nanoparticles have been widely presented as nanocarriers to help the delivery of gene, drugs, and other therapeutic agents with cellular targeting ability. Advances in the understanding of gene delivery and RNA interference (RNAi)-based therapy have brought increasing attention to understanding and tackling complex genetically related diseases, such as cancer, cardiovascular and pulmonary diseases, autoimmune diseases and infections. The combination of nanocarriers and DNA/RNA delivery may potentially improve their safety and therapeutic efficacy. However, there still exist many challenges before this approach can be practiced in the clinic. In this review, we provide a comprehensive summary on the types of nanoparticle systems used as nanocarriers, highlight the current use of nanocarriers in recombinant DNA and RNAi molecules delivery, and the current landscape of gene-based nanomedicine-ranging from diagnosis to therapeutics. Finally, we briefly discuss the biosafety concerns and limitations in the preclinical and clinical development of nanoparticle gene systems.

11.
Org Biomol Chem ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774099

RESUMO

An efficient protocol to synthesize 3-alkylated quinoxalin-2(1H)-ones through photocatalytic decarboxylation coupling reactions of quinoxalin-2(1H)-ones with N-hydroxyphthalimide ester was developed. The control experiment showed that a radical was involved in this transformation. This approach provides an alternative way to obtain various valuable corresponding products in moderate-to-good yields.

12.
J Biol Chem ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31662436

RESUMO

DNA methylation and histone modifications critically regulate the expression of many genes and repeat regions during spermatogenesis. However, the molecular details of these processes in male germ cells remain to be addressed. Here, using isolated murine sperm cells, ultra-low-input native ChIP -Seq (ULI-NChIP-Seq), and Whole Genome Bisulfite Sequencing (WGBS), we investigated genome-wide DNA methylation patterns and histone 3 Lys-9 trimethylation (H3K9me3) modifications during mouse spermatogenesis. We found that DNA methylation and H3K9me3 have distinct sequence preferences and dynamics in promoters and repeat elements during spermatogenesis. H3K9me3 modifications in histones at gene promoters were highly enriched in round spermatids. H3K9me3 modification on long terminal repeats (LTRs) and long interspersed nuclear elements (LINEs) was involved in silencing active transcription from these regions in conjunction with reestablishment of DNA methylation. Furthermore, H3K9me3 remodeling on the X chromosome was involved in meiotic sex chromosome inactivation (MSCI) and in partial transcriptional reactivation of sex chromosomes in spermatids. Our findings also revealed the DNA methylation patterns and H3K9me3 modification profiles of paternal and maternal germline imprinting control regions (gICRs) during spermatogenesis. Taken together, our results provide a genome-wide map of H3K9me3 modifications during mouse spermatogenesis that may be helpful for understanding male reproductive disorders.

13.
Eur J Med Chem ; 183: 111737, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581002

RESUMO

A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50 = 1.3 ±â€¯0.01 µM) and butyrylcholinesterase (IC50 = 1.2 ±â€¯0.09 µM). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57 ±â€¯0.01 µM. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced Aß1-42 aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu2+-induced Aß1-42 aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, Aß1-42 and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD.

15.
Sci Rep ; 9(1): 14315, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586114

RESUMO

Although numerous attempts have been made to alter the sex ratio of the progeny of mammals, the limitations of current technologies have prevented their widespread use in farm animals. The presence or absence of a Y chromosome determines whether a mammalian embryo develops as a male or female, and non-invasive genetic reporters such as fluorescence protein markers have been intensively applied in a variety of fields of research. To develop a non-invasive and instantaneous method for advance determination of the sex of embryos, we developed a Y chromosome-linked eGFP mouse line that stably expresses green fluorescent protein under the control of the CAG promoter. The development of the CRISPR/Cas9 system has made it easy to deliver an exogenous gene to a specific locus of a genome, and linking a tracer to the Y chromosome has simplified the process of predicting the sex of embryos collected by mating a Y-Chr-eGFP transgenic male with a wild-type female. XY embryos appeared green, under a fluorescence microscope, and XX embryos did not. Y chromosome-linked genes were amplified by nested PCR to further confirm the accuracy of this method, and the simultaneous transplantation of green and non-green embryos into foster mothers indicated that 100% accuracy was achieved by this method. Thus, the Y-Chr-eGFP mouse line provides an expeditious and accurate approach for sexing pre-implantation embryos and can be efficiently used for the pre-selection of sex.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31597496

RESUMO

Purpose: This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer. Methods: A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty. Results: Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490 per QALY. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,727 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters. Conclusion: Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

17.
Aging (Albany NY) ; 11(19): 8204-8216, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581131

RESUMO

Recently, an increasing number of studies have reported that dysregulation of long noncoding RNAs (lncRNAs) plays an important role in cancer initiation and progression, including in epithelial ovarian carcinoma (EOC). However, little is known about the detailed biological functions of the lncRNA small nucleolar RNA host gene 22 (SNHG22) during the progression of EOC. Here, we found that SNHG22 was significantly increased in EOC tissues and was significantly associated with a low level of differentiation. Forced SNHG22 expression promoted chemotherapy resistance in EOC cells. Knockdown of SNHG22 expression increased the sensitivity of EOC cells to cisplatin and paclitaxel. Importantly, we found that SNHG22 could directly interact with miR-2467 and lead to the release of miR-2467-targeted Gal-1 mRNA. Moreover, SNHG22 overexpression induced EOC cell resistance to chemotherapy agents via PI3K/AKT and ERK cascade activation. In summary, our findings demonstrate that SNHG22 plays a critical role in the chemotherapy resistance of EOC by mediating the miR-2467/Gal-1 regulatory axis.

18.
Microb Pathog ; 138: 103808, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31634530

RESUMO

Iron plays a central role at the interface of pathogen and host. The ability to sequester iron from a host not only reduces host immune defenses but also promotes pathogen virulence, leading to the occurrence of infectious disease. Recently, outer membrane protein OmpW was shown to protect bacteria against harsh environmental conditions and to play a role in infectious disease. The expression of this versatile protein is controlled by iron, but the underlying mechanism of iron regulation has not been elucidated. In this study, the relation between OmpW expression and iron was investigated. Our results demonstrated that expression of OmpW is responsive to iron. Iron uptake analysis showed that an ompW mutant strain has a strong requirement for iron as compared to wild type and the ompW complemented strain. Moreover, ferric uptake regulation protein Fur, an iron binding transcriptional factor, was downregulated under iron limitation conditions and had a similar expression profile to OmpW in the presence or absence of iron. Based on these results, we suggest that iron regulates OmpW by binding to Fur. Furthermore, SoxS, a transcriptional factor involved in oxidative stress, was found to negatively regulate OmpW. We found that downregulating or knocking out OmpW results in bacterial resistance to oxidative stress. These findings provide new insight into the regulation of OmpW expression by iron, and may represent a new mechanism contributing to iron-mediated infectious disease.

19.
J Exp Clin Cancer Res ; 38(1): 409, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533816

RESUMO

BACKGROUND: ATPase associated with a variety of cellular activities (AAA ATPase) family members are closely linked to tumor formation and progression. However, their roles in hepatocellular carcinoma (HCC) largely remain unclear. METHODS: Bioinformatic analyses of public databases were used to excavate the potential AAA ATPases that may contribute to HCC, and thyroid hormone receptor interactor 13 (TRIP13) was selected to following researches because of its most prominently differential expression. Western blot, qRT-PCR and immunohistochemistry were used to detect the expression of TRIP13 in HCC tissues, and then the relationship between TRIP13 expression and clinicopathological parameters were evaluated. Finally, its functions and potential mechanisms were investigated through a series gain- and loss-of-function strategies both in vitro and in vivo. RESULTS: TRIP13 was significantly overexpressed in HCC tissues and high level of TRIP13 was closely correlated with a worse clinical outcome. Functionally, elevated TRIP13 facilitated cell proliferation, migration, invasion, and promoted cellular epithelial-mesenchymal transition (EMT) in vitro, while promote tumor growth and lung metastasis in vivo. Mechanistically, TRIP13 interacted with ACTN4 and positively regulated its expression, thus activating the AKT/mTOR pathway to drive tumor progression. Moreover, miR-192-5p served as an upstream regulator of TRIP13 by directly binding to TRIP13 mRNA 3' UTR, which may partially explain the high expression of TRIP13 in HCC. CONCLUSION: Our findings identified TRIP13 as a promising candidate oncogene in HCC, and TRIP13 induced cell migration, invasion and metastasis of HCC through the AKT/mTOR signaling via interacting with ACTN4.

20.
J Agric Food Chem ; 67(43): 11893-11900, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31542926

RESUMO

To explore a novel fungicide effectively against cucumber downy mildew (CDM), a series of new arylpyrazole containing pyrimidine ether derivatives were designed and synthesized by employing the intermediate derivatization method (IDM). The structures of synthesized compounds were identified by 1H NMR, 13C NMR, elemental analyses, MS, and X-ray diffraction. Bioassays demonstrated that some of the title compounds exhibited excellent fungicidal activities against CDM. Especially, compound 7 (EC50 = 1.22 mg/L) displayed significantly higher bioactivity than that of commercial fungicides diflumetorim and flumorph and nearly equal effect to that of cyazofamid. The relationship between the structure and fungicidal activity of the synthesized compounds was discussed as well. The study showed that compound 7 was a promising fungicide candidate for further development.

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