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1.
Chemosphere ; 238: 124640, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524609

RESUMO

Triclosan (TCS) is a kind of chronic toxicity to aquatic organisms. Due to its highly effective antimicrobial, TCS has been widely applied in personal-care products, which naturally poses a potential risk to the ecological system and human health since its release into water-ecological environment. Therefore, it urgently demands a selective, easily separated, recyclable, and low-cost adsorbent to remove the residues of TCS from aquatic environments. In this study, a novel magnetic molecularly imprinted nano-polymers (TMIPs) were prepared for selective adsorption and convenient collection of TCS in aquatic samples, based on a core-shell technique using TCS as template molecule and SiO2-coated Fe3O4 nanoparticles as the support substrate. The functional groups, particle size, morphology and magnetic property of TMIPs were characterized by Fourier-transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy and vibrating sample magnetometer, respectively. The obtained TMIPs possessed excellent adsorption capacity (Qe = 53.12 mg g-1), speedy adsorption equilibrium time (2 min) and high selectivity (k' = 6.321) for TCS. Moreover, the pH-tolerance and stability tests manifested that the adsorption capacity of TMIPs for TCS was acid-resistance and could retain 94.2% of the maximum Qe after 5 times removal-regeneration cycles. The feature of magnetically susceptibility can simplify the procedures of sample handling in TCS determination, because the TMIPs of TCS are easy to be recycled from aquatic samples. As an application demonstration, the toxicity test in microalgae confirmed that a tiny amount of TMIPs could significantly eliminate the toxic effect of TCS on Chlamydomonas reinhardtii via the efficient binding with TCS.

2.
Carbohydr Polym ; 228: 115372, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635745

RESUMO

This study aimed at providing a novel approach for improving the physicochemical stability and solubility of algal oil nanocapsules through formation of electrostatic interactions and prebiotic carbohydrates systems composed of: octenyl-succinic anhydride (OSA) starch, OSA/inulin (IN), OSA/maltodextrin (MD), OSA/chitosan (CS), OSA/MD/IN, and OSA/CS/IN. IN, a functional prebiotic modifier, was found to significantly (p < 0.05) decrease emulsion viscosity and particle size, with OSA/CS/IN particles having significantly (p < 0.05) improved water solubility (4.96%) and wettability (749 s) compared to OSA/CS particles. Interestingly, OSA/CS/IN particles had the highest oxidative stability (three times that of bulk oil) and encapsulation efficiency (98.57%). OSA/CS/IN particles were also more hygroscopic than pure OSA particles. Furthermore, scanning electron microscopy (SEM) revealed OSA/CS/IN particles had less wrinkled, smoother surfaces, providing lower air permeability and better protection. Therefore, OSA/CS/IN, as a prebiotic encapsulation system, may lead to the value addition of algal oil.

3.
Methods Mol Biol ; 2072: 85-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31541440

RESUMO

cis-regulatory DNA elements (CREs) are noncoding but functional DNA sequences. The binding of regulatory proteins into CRE regions leads to chromatin high sensitive to DNase I digestion, which are termed as DNase I hypersensitive sites (DHSs). These DHSs can be efficiently detected through DNase I digestion followed by high-throughput DNA sequencing (DNase-seq). Thus, DNase-seq has become a powerful technique for DHSs mapping at whole-genome level in both plants and animals. Here we describe a DNase-seq procedure modified and developed for crop plants. These plants usually contain large amounts of repetitive sequences and complex organic constituents. With the main improvement in nuclei isolation, this method has been successfully used in mapping DHSs in cotton and sugarcane.

4.
Chem Commun (Camb) ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675017

RESUMO

Presented here is the deep eutectic solvothermal synthesis of an open framework copper selenidogermanate, namely [NH3CH3]0.75Cu1.25GeSe3 (CuGeSe-1), which exhibits a rapid and effective Cs+ ion exchange performance (qm = 225.3 mg g-1). CuGeSe-1 shows a structural flexibility upon Cs+ exchange. The robust selenide-based framework contributes to an excellent pH stability (1-12). The Cs+-laden product could be facilely eluted.

5.
Int J Mol Sci ; 20(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683725

RESUMO

Agrobacterium-mediated genetic transformation is well established in the model grass Brachypodium distachyon. However, most protocols employ immature embryos because of their better regenerative capacity. A major problem associated with the immature embryo system is that they are available only during a limited time window of growing plants. In this study, we have developed an optimized Agrobacterium-mediated genetic transformation protocol that utilizes mature embryos. We have adopted seed shearing and photoautotrophic rooting (PR) in callus induction and root regeneration, respectively, with evident significant improvement in these aspects. We have also revealed that the newly developed chemical inducer Fipexide (FPX) had the ability to induce callus, shoots, and roots. By comparison, we have demonstrated that FPX shows higher efficiency in shoot generation than other frequently used chemicals in our mature embryo-based system. In addition, we demonstrated that the age of embryogenetic callus severely affects the transformation efficiency (TE), with the seven-week-old embryogenetic callus having the highest TE reaching 52.6%, which is comparable with that in immature embryo transformation. The new methodologies reported here will advance the development and utilization of Brachypodium as a new model system for grass genomics.

6.
J Agric Food Chem ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675227

RESUMO

α-Dicarbonyl compounds (α-DCs) are a major class of intermediates generated during Maillard reactions. They can serve as chemical markers of thermal processing and storage of sugar-rich foods. In order to distinguish between naturally matured acacia honey (NMAH) and artificially heated acacia honey (AHAH), we purified 12 major α-DCs quinoxaline derivatives to investigate the effects of temperature during heat treatment and storage on their accumulation in acacia honey. Nine of the twelve α-dicarbonyl compounds were found in acacia honey samples and their contents varied depending on processing and storage conditions. Among them, the contents of 3-deoxyglucosulose (3-DG), 1,4-dideoxyglucosone (1,4-DDG), and 1-deoxyglucosone (1-DG) increased commensurately with heat. 3-DG content ranged from 103.7-146.6 mg/kg in NMAH and 572.4-1371.2 mg/kg in AHAH. Given the abundance and stability of 3-DG following heat treatment and storage, this compound can potentially serve as a reliable marker for distinguishing between NMAH and AHAH.

7.
Gene ; : 144169, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669642

RESUMO

BACKGROUND (OBJECTIVE): In the development of tumor therapy, the role of long non-coding RNA actin filagenin 1 antisense RNA 1 (1ncRNA AFAP1-AS1) is quite significant, but the actual role of AFAP1-AS1 in the treatment of prostate cancer has not been determined. In view of this, the author took AFAP1-AS1 as the research object to design an experimental study, and conducted an in-depth exploration of the pathogenesis of prostate cancer. METHODS: RT-qPCR was used to detect the expression of AFAP1-AS1 and miR-512-3p in prostate cancer tissues and cell lines. Perforation, flow cytometry and CCK-8 were used to detect the effects of cell proliferation, migration and invasion of mir-512-3p and a AFAP1-AS1. And the luciferase reporter gene was used to detect the downstream target gene of AFAP1-AS1, and the expression of CDK4, CDK6 and CCND1 protein was detected by Western blot. RESULTS: AFAP1-AS1 is highly expressed in prostate cancer tissues and cell lines. The expression level of AFAP1-AS1 is correlated with histological grade and distant metastasis. The overall level of patients with high expression of AFAP1-AS1 is low, and their survival rate is relatively low. Silencing AFAP1-AS1 can significantly increase the proliferation and migration of prostate cancer cells. AFAP1-AS1 silencing induces cell cycle arrest at G0/G1 phase. The downstream target of AFAP1-AS1 was mir-512-3p. The role of AFAP1-AS1 in the progression of prostate cancer cells was mediated by mir-512-3p. CONCLUSION: AFAP1-AS1 regulates miR-512-3p, so as to realize the regulation effect on the proliferation, invasion and migration of prostate cancer cells, and thereby promote the occurrence and development of prostate cancer, so as to provide the corresponding program for the treatment of prostate cancer. Abberivation: ADPC, androgen-dependent prostate cancer; CRPC, castrated prostate cancer; RNA1 AFAP1-Asl, Actin fiber-associated protein 1-anti-RNA1; miRNAs, MicroRNAs.

8.
Glob Chang Biol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670435

RESUMO

With accumulation of carbon cycle observations and model developments over the past decades, exploring interannual variations (IAV) of terrestrial carbon cycle offers the opportunity to better understand climate-carbon cycle relationships. However, despite growing research interest, uncertainties remain on some fundamental issues, such as the contributions of different regions, constituent fluxes and climatic factors to carbon cycle IAV. Here, we overviewed the literature on carbon cycle IAV about current understanding of these issues. Observations and models of the carbon cycle unanimously show the dominance of tropical land ecosystems to the signal of global carbon cycle IAV, where tropical semi-arid ecosystems contribute as much as the combination of all other tropical ecosystems. Vegetation photosynthesis contributes more than ecosystem respiration to IAV of the global net land carbon flux, but large uncertainties remain on the contribution of fires and other disturbance fluxes. Climatic variations are the major driver to the IAV of net land carbon flux. Although debate remains on whether the dominant driver is temperature or moisture variability, their interaction, i.e. the dependence of carbon cycle sensitivity to temperature on moisture conditions, is emerging as key regulators of the carbon cycle IAV. On time-scales from the interannual to the centennial, global carbon cycle variability will be increasingly contributed by northern land ecosystems and oceans. Therefore, both improving Earth system models (ESMs) with the progressive understanding on the fast processes manifested at interannual time-scale and expanding carbon cycle observations at broader spatial and longer temporal scales are critical to better prediction on evolution of the carbon-climate system.

9.
Nucleic Acids Res ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680137

RESUMO

ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- or territory-centric manner. Advanced genomic browsers integrate the genetic features surrounding genes or gene sets within a species. A Genomicus synteny browser explores the conservation of local gene order across deuterostome. This new release covers an extended taxonomic range of 14 species, including for the first time a non-ascidian species, the appendicularian Oikopleura dioica. Functional annotations, provided for each species, were enhanced through a combination of manual curation of gene models and the development of an improved orthology detection pipeline. Finally, gene expression profiles and anatomical territories can be explored in 4D online through the newly developed Morphonet morphogenetic browser.

10.
J Exp Clin Cancer Res ; 38(1): 438, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666108

RESUMO

BACKGROUND: Glutathione S-transferase zeta 1 (GSTZ1) is the penultimate enzyme in phenylalanine/tyrosine catabolism. GSTZ1 is dysregulated in cancers; however, its role in tumorigenesis and progression of hepatocellular carcinoma (HCC) is largely unknown. We aimed to assess the role of GSTZ1 in HCC and to reveal the underlying mechanisms, which may contribute to finding a potential therapeutic strategy against HCC. METHODS: We first analyzed GSTZ1 expression levels in paired human HCC and adjacent normal tissue specimens and the prognostic effect of GSTZ1 on HCC patients. Thereafter, we evaluated the role of GSTZ1 in aerobic glycolysis in HCC cells on the basis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Furthermore, we assessed the effect of GSTZ1 on HCC proliferation, glutathione (GSH) concentration, levels of reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (NRF2) signaling via gain- and loss- of GSTZ1 function in vitro. Moreover, we investigated the effect of GSTZ1 on diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) induced hepatocarcinogenesis in a mouse model of HCC. RESULTS: GSTZ1 was downregulated in HCC, thus indicating a poor prognosis. GSTZ1 deficiency significantly promoted hepatoma cell proliferation and aerobic glycolysis in HCC cells. Moreover, loss of GSTZ1 function depleted GSH, increased ROS levels, and enhanced lipid peroxidation, thus activating the NRF2-mediated antioxidant pathway. Furthermore, Gstz1 knockout in mice promoted DEN/CCl4-induced hepatocarcinogenesis via activation of the NRF2 signaling pathway. Furthermore, the antioxidant agent N-acetylcysteine and NRF2 inhibitor brusatol effectively suppressed the growth of Gstz1-knockout HepG2 cells and HCC progression in Gstz1-/- mice. CONCLUSIONS: GSTZ1 serves as a tumor suppressor in HCC. GSH depletion caused by GSTZ1 deficiency elevates oxidative stress, thus constitutively activating the NRF2 antioxidant response pathway and accelerating HCC progression. Targeting the NRF2 signaling pathway may be a promising therapeutic approach for this subset of HCC.

11.
Ultrason Sonochem ; 61: 104819, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669844

RESUMO

Facet engineering of nanocomposite has been confirmed to be an efficient strategy to accelerate their catalytic performances, but to improve their piezoelectric catalytic activities by facet engineering has been seldom reported. Herein, we developed a series of SrTiO3 nanocrystals with exposed {0 0 1} facet, dominant {1 1 0} facet and co-exposed {0 0 1} and {1 1 0} facets, respectively, and firstly revealed its piezoelectric catalytic performance under ultrasonic vibration. Moreover, the relationship between piezoelectric-induced catalytic activity and facet-dependence of SrTiO3 nanocrystal was disclosed for the first time. The SrTiO3 nanocrystal with co-exposed {0 0 1} and {1 1 0} facets exhibited effectively enhanced piezoelectric catalytic activity by degrading Rhodamine B (RhB) under ultrasonic vibration, as compared to that of SrTiO3 nanocrystals with exposed {0 0 1} facet and dominant {1 1 0} facet, respectively. In addition, trapping experiments and active species quantitative experiments confirmed that the co-exposed {0 0 1} and {1 1 0} facets were beneficial to produce O2- and OH with the generation rates of 8.3 and 132.2 µmol g-1 h-1, respectively. The OH radical played a dominant role in piezoelectric catalytic process. Finally, the piezoelectric catalysis mechanism of SrTiO3 surface heterojunction was proposed based on a DFT study. This study presents an in-depth understanding of piezoelectric-induced catalytic of perovskite nanocrystals with exposed well-defined facets.

12.
Plant Physiol Biochem ; 145: 153-163, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31693975

RESUMO

The aim of this work was exploring the effects of silicon, selenium, and a microorganism fertilizer on alleviating the effects of lead (Pb) toxicity in ginger. Ginger plants were grown in soil containing 500 mg/kg Pb(NO3)2 without (CK) or with Si, Se, or microorganism fertilizer (T1, T2, T3) as soil conditioners. Morphology indexes, Pb accumulation and distribution rates, and antioxidant enzyme activities were investigated. The Pb transfer and Pb absorption coefficients were calculated, and Pb accumulation in plant organs at various developmental stages were determined. All three soil conditioners alleviated Pb stress in ginger plants. The rhizome fresh weight in T1, T2, and T3 was increased by 96.06, 85.81, and 41.58%, respectively, compared with CK. The accumulation of Pb in organs was lower in all treatments than in CK. The chlorophyll and carotenoid contents in leaves, and root activity, root length, and the tolerance index, were higher in the treatments than in CK. The reactive oxygen species content in ginger leaves and roots was significantly lower in all treatments than in CK. Soil conditioners alleviated the negative effects of Pb stress on ginger plants: Si was the most effective, followed by Se, and then the microorganism fertilizer.

13.
Hum Mutat ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705731

RESUMO

Exonic deletions and duplications within DMD are the main pathogenic variants in Duchenne and Becker muscular dystrophies (DMD/BMD). However, few studies have profiled the flanking sequences of breakpoints and the potential mechanism underlying the breakpoints in different fragile regions of DMD. In this study, 896 Chinese male probands afflicted with DMD/BMD were selected from unrelated families and analyzed using multiplex ligation-dependent probe amplification of the DMD gene, in which we identified exon deletions in 784 subjects and duplications in 112 subjects. Deletions occurred most frequently in the genomic region encompassing exons 45-55, accounting for 72% (576/784) of all deletion patterns. Further, in order to unravel the potential mechanism that induced breaks, DMD gene capture and sequencing were performed to identify the breakpoints in 37 subjects with deletions encompassing exons 45-55 of DMD; we found that DMD instability did not arise from a single cause; instead, long-sequence-motifs, nonconsensus microhomologies, low-copy repeats and micro indels were embedded around the breakpoints, which may predispose DMD to instability. In summary, our study highlights the heterogeneous characteristics of the flanking sequences around the breakpoints and help understand the mechanism underlying DMD gene instability. This article is protected by copyright. All rights reserved.

14.
BMC Pediatr ; 19(1): 412, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31690282

RESUMO

PURPOSE: To review our experience with pediatric congenital buttock sinus tract, and to conclude the clinical characteristics and management of the disease. METHODS: Twenty-two pediatric patients diagnosed with congenital buttock sinus tract were included. Medical records were reviewed, and the patients were followed up. Continuous variables were presented by median and range. Categorical variables were presented as frequencies and percentages. RESULTS: Among the 22 patients, there were 8 boys (36.4%) and 14 girls (63.6%). The median first onset age was 42 months, and the range was 5 months to 12 years old. Admission age was 69.5 months, with a range from 14 months to 12 years old. Overall prior treatment time was 11 months, ranging from 3 months to 11 years. Twenty-one patients had definite congenital dimples since birth, and later manifested with infection through the dimple. All patients came to the doctor with complaint of the infection. The number of invasive procedures ranged from 0 to 5, with an average of 2. Radiology could exactly display the morphology and show the termination as a retrorectal cyst. The surgical procedure was adopted trans-fistula tract, and the pathological results showed a dermoid cyst in 11 patients and an epidermoid cyst in 10 patients. During the follow-up period of 34.5 months (range, 2 months to 8 years), 19 patients were uneventful and 3 patients suffered recurrence. Two of them underwent a second operation and had no recurrence ever since. The third patient did not receive a second operation, and the refractory infection was still present. CONCLUSIONS: Pediatric congenital buttock sinus tract is rare and has a female predominance in the morbidity. Patients have a distinctive congenital dimple on the buttock with recurrent infection, and there usually exists a congenital sinus tract from the dimple to the retrorectal space. Total excision is the only method for the cure. The nature of the disease is a retrorectal developing dermoid cyst or epidermoid cyst.

15.
Sci Rep ; 9(1): 16088, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695091

RESUMO

Fencing for grazing exclusion has been widely found to have an impact on grassland soil organic carbon (SOC) and total nitrogen (TN), but little is known about the impact of fenced grassland on the changes in deep soil carbon (C) and nitrogen (N) stocks in temperate grasslands. We studied the influence of 30 years fencing on vegetation and deep soil characteristics (0-500 cm) in the semi-arid grasslands of northern China. The results showed that fencing significantly increased the aboveground biomass (AGB), litter biomass (LB), total biomass, vegetation coverage and height, and soil water content and the SOC and TN in the deep soil. The belowground biomass (BGB) did not significantly differ between the fenced and grazed grassland. However, fencing significantly decreased the root/shoot ratio, forbs biomass, pH, and soil bulk density. Meanwhile, fencing has significantly increased the C and N stocks in the AGB and LB but not in the BGB. After 30 years of fencing, the C and N stocks significantly increased in the 0-500 cm soil layer. The accumulation of SOC mainly occurred in the deep layers (30-180 cm), and the accumulation of TN occurred in the soil layers of 0 to 60 cm and 160 to 500 cm. Our results indicate that fencing is an effective way to improve deep soil C and N stocks in temperate grassland of northwest China. There were large C and N stocks in the soil layers of 100 to 500 cm in the fenced grasslands, and their dynamics should not be ignored.

16.
J Pineal Res ; : e12615, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605630

RESUMO

Abnormal proliferation and motility of retinal pigment epithelial cells leads to proliferative vitreoretinopathy (PVR). Melatonin is a known effective antitumour and anti-invasive agent, but whether it affects the formation and underlying mechanisms of PVR remains unclear. In this study, the results of the MTT assay, colony formation, and propidium iodide (PI) staining with flow cytometry revealed that melatonin dose dependently inhibited epidermal growth factor (EGF)-induced proliferation of human ARPE-19 cells. Furthermore, melatonin reduced EGF-induced motility by suppressing cathepsin S (CTSS) expression. Pretreatment with ZFL (a CTSS inhibitor) or overexpression of CTSS (pCMV-CTSS) significantly inhibited EGF-induced cell motility when combined with melatonin. EGF induced the phosphorylation of AKT(S473)/mTOR (S2448) and transcription factor (c-Jun/Sp1) signalling pathways. Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF-induced motility and p-AKT/p-mTOR/c-Jun/Sp1 expression when combined with melatonin. Taken together, these data indicate that melatonin inhibited EGF-induced proliferation and motility of human ARPE-19 cells by activating the AKT/mTOR pathway, which is dependent on CTSS modulation of c-Jun/Sp1 signalling. Melatonin may be a promising therapeutic drug against PVR.

17.
Indoor Air ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605641

RESUMO

Endotoxin exacerbates asthma. We designed the Louisa Environmental Intervention Project (LEIP) and assessed its effectiveness in reducing household endotoxin and improving asthma symptoms in rural Iowa children. Asthmatic schoolchildren (N=104 from 89 homes) of Louisa and Keokuk counties in Iowa (aged 5-14 years-old) were recruited and block-randomized to receive extensive (education + professional cleaning) or educational interventions. Environmental sampling collection and respiratory survey administration were done at baseline and during three follow-up visits. Mixed-model analyses were used to assess the effect of the intervention on endotoxin levels and asthma symptoms in the main analysis and of endotoxin reduction on asthma symptoms in exploratory analysis. In the extensive intervention group, dust endotoxin load was significantly reduced in post-intervention visits. The extensive compared to the educational intervention was associated with significantly decreased dust endotoxin load in farm homes and less frequent nighttime asthma symptoms. In exploratory analysis, dust endotoxin load reduction from baseline was associated with lower total asthma symptoms score (Odds ratio: 0.52, 95% confidence interval: 0.29-0.92). In conclusion, the LEIP intervention reduced household dust endotoxin and improved asthma symptoms. However, endotoxin reductions were not sustained post-intervention by residents.

19.
Cell Death Dis ; 10(11): 815, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653826

RESUMO

Targeting oncogenic proteins for degradation using proteolysis-targeting chimera (PROTAC) recently has drawn increasing attention in the field of cancer research. Bromodomain and extra-terminal (BET) family proteins are newly identified cancer-related epigenetic regulators, which have a role in the pathogenesis and progression of osteosarcoma. In this study, we investigated the in vitro and in vivo anti-osteosarcoma activity by targeting BET with a PROTAC molecule BETd-260. The results showed that BETd-260 completely depletes BET proteins and potently suppresses cell viability in MNNG/HOS, Saos-2, MG-63, and SJSA-1 osteosarcoma cell lines. Compared with BET inhibitors HJB-97 and JQ1, the activity of BETd-260 increased over 1000 times. Moreover, BETd-260 substantially inhibited the expression of anti-apoptotic Mcl-1, Bcl-xl while increased the expression of pro-apoptotic Noxa, which resulted in massive apoptosis in osteosarcoma cells within hours. In addition, pro-oncogenic protein c-Myc also was substantially inhibited by BETd-260 in the OS cells. Of note, BETd-260 induced degradation of BET proteins, triggered apoptosis in xenograft osteosarcoma tumor tissue, and profoundly inhibited the growth of cell-derived and patient-derived osteosarcoma xenografts in mice. Our findings indicate that BET PROTACs represent a promising therapeutic agent for human osteosarcoma.

20.
BMC Vet Res ; 15(1): 373, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660972

RESUMO

BACKGROUND: Fowl adenovirus outbreaks have occurred in China since June 2015. This virus is an emerging infectious disease that causes hydropericardium syndrome and inclusion body hepatitis (HPS-IBH), resulting in significant economic loss to poultry farmers. Five fowl adenovirus (FAdV) strains (HN, AQ, AH726, JS07 and AH712) were isolated from Jiangsu and Anhui provinces. RESULTS: Phylogenetic analysis revealed that the five isolates belonged to species C fowl adenovirus serotype 4. An 11 amino-acid deletion in ORF29, relative to an older viral isolate, JSJ13, was observed for all five strains described here. In chicken experiments, 80-100% birds died after intramuscular inoculation and displayed lesions characteristic of HPS-IBH. The viral DNA copies were further detected by hexon-probe based real-time polymerase chain reaction (PCR) in the chicken samples. The viral loads and cytokine profiles were recorded in all the organs after infections. Despite minor genetic differences, the 5 strains displayed significantly different tissue tropisms and cytokine profiles. CONCLUSIONS: Our data enhance the current understanding some of the factors involved in the pathogenicity and genetic diversity of the FAdV serotype 4 (FAdV-4) in China. Our work provides theoretical support for the prevention and control of HPS-IBH in chickens.

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