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1.
Plant Dis ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393361

RESUMO

Glomerella leaf spot (GLS) is a devastating fungal disease causing pre-mature defoliation on apple (Malus domestica). It was first reported in 1970s and since then has been reported in North America, South America and Asia. GLS disease is caused by Colletotrichum fungi and the pathogens are genetically diverse, encompassing at least nine species belonging to three species complexes (Velho et al. 2018). In August 2018, disease with sudden leaf necrosis symptom, typical of GLS symptom appearance, occurred in a Granny Smith orchard in Wugong county, China, over 70% tree leaves bared brown and necrotic lesions. Small leaf tissues (3-4 mm2) cut from lesion margins were surface sterilized for 30 s in 3% NaClO and 30 s in 75% ethanol, followed by rinsing three times in sterile water before transferring onto potato dextrose agar (PDA) plates (25 ± 2°C). Seven isolates were obtained, all producing round cottony colonies on PDA, being white to pale on the upper side and dark green on the reverse side. Conidia were single-celled, cylindrical and transparent (17.33 ± 1.29 × 5.11 ± 0.77 µm, n=50). Appressoria were single-celled, thick-walled, dark brown, oval or irregular shaped, sometimes lobed (9.07 ± 0.88 × 6.66 ± 0.33 µm, n=50). The morphological and cultural characteristics of the fungal isolates matched the descriptions of Colletotrichum aenigma (Weir et al. 2012). To confirm the species identity, genomic DNAs were isolated from two representative isolates (QSG1 and QSY1), and the internal transcribed spacer (ITS), actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-tubulin (TUB2), manganese-superoxide dismutase (SOD2), chitin synthase (CHS), and calmodulin (CAL) regions were amplified by PCR using reported primers (Weir et al. 2012). The sequences were deposited in GenBank (Accession Nos. MT872061, MT873580, MT873581, MT888183, MT888185, MT888187 and MT888189 for QSG1, and MT834933, MT835166, MT873579, MT888182, MT888184, MT888186 and MT888188 for QSY1). BLASTn search against GenBank nr database showed that ITS sequences of the two strains showed high nucleotide identity (over 99%) to sequences derived from the Colletotrichum gloeosporioides species complex (CGSC). Further concatenated phylogenetic analysis with reported CGSC strains (Weir et al. 2012) placed QSG1 and QSY1 in the clade of C. aenigma. To fulfill Koch's postulates, field pathogenicity test was performed. The experiment was performed in an orchard located in Yangling in September 2020, with the daily average temperature ranging between 15 - 20 ℃. Healthy 'Granny Smith' leaves were surface sterilized with 70% alcohol and inoculated with conidial suspension (106 conidia/mL) using cotton swabs. For each isolate, 10 leaf inoculations were performed. Inoculation with distilled water served as a negative control. Inoculated leaves were covered with plastic bags to maintain high humidity and the bags were removed at 48 hours post inoculation (hpi). Conidium-inoculated leaves started to exhibit GLS-resembling necrotic lesions from 5 dpi onward. The lesion extent, however, varied among inoculated leaves, ranging from blurry, small-sized lesions to blight of entire leaf. In contrast with conidium inoculations, water-inoculated leaves remained asymptomatic until 14 dpi. Re-isolated fungi from the symptomic leaf tissues were identical to C. aenigma in morphological appearance. Taken together, this is the first report of GLS on 'Granny Smith' apple, and the first report of C. aenigma causing apple GLS in China. This information should provide important guideline for developing field control practices of GLS.

2.
Ecotoxicol Environ Saf ; 207: 111541, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254401

RESUMO

Ammonia has been of concern for its high toxicity to aquatic species and frequent detection in waters worldwide. This study calculated the national aquatic life criteria for ammonia in China. The temporal and spatial distributions were investigated and the multi-tier ecological risks were assessed for ammonia and un-ionized ammonia (NH3) during 2014-2018 based on a total of 18989 ammonia monitoring data from 110 monitoring sites in seven river basins. The sensitivity comparison of different species taxa to ammonia showed that Perciformes fish should be listed as a priority protected species in the derivation of ammonia criteria. The participation of introduced aquaculture species have no significant impact on the final criteria values (t-test, p > 0.05). The final criterion maximum concentration (CMC) and criterion continuous concentration (CCC) were 10.24 and 3.31 mg/L for ammonia (pH 7.0 and 20 °C). The interannual variation showed that decreasing trends were observed for ammonia and NH3 pollutions in the past five years. However, the increasing trends were observed for ammonia in Liao River basin, for NH3 in Yangtze River and Pearl River basins (2014-2018). The significant seasonal and geographical differences of ammonia and NH3 pollution were found. Moreover, the pollutions of ammonia and NH3 in some monitoring points of Huai River, Yellow River and Songhua River basins at the provincial borders were significant. The result of ecological risk assessment showed that the average exceedance probability for 5% affected species by NH3 in long-term exposure was 28.96% in the past five years.


Assuntos
Amônia/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Amônia/toxicidade , Animais , China , Ecossistema , Peixes , Água Doce , Medição de Risco , Rios , Poluentes Químicos da Água/toxicidade
3.
Bone Joint Res ; 9(12): 840-847, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33275035

RESUMO

AIMS: Restoration of proximal medial femoral support is the keystone in the treatment of intertrochanteric fractures. None of the available implants are effective in constructing the medial femoral support. Medial sustainable nail (MSN-II) is a novel cephalomedullary nail designed for this. In this study, biomechanical difference between MSN-II and proximal femoral nail anti-rotation (PFNA-II) was compared to determine whether or not MSN-II can effectively reconstruct the medial femoral support. METHODS: A total of 36 synthetic femur models with simulated intertrochanteric fractures without medial support (AO/OTA 31-A2.3) were assigned to two groups with 18 specimens each for stabilization with MSN-II or PFNA-II. Each group was further divided into three subgroups of six specimens according to different experimental conditions respectively as follows: axial loading test; static torsional test; and cyclic loading test. RESULTS: The mean axial stiffness, vertical displacement, and maximum failure load of MSN-II were 258.47 N/mm (SD 42.27), 2.99 mm (SD 0.56), and 4,886 N (SD 525.31), respectively, while those of PFNA-II were 170.28 N/mm (SD 64.63), 4.86 mm (SD 1.66), and 3,870.87 N (SD 552.21), respectively. The mean torsional stiffness and failure torque of MSN-II were 1.72 N m/° (SD 0.61) and 16.54 N m (SD 7.06), respectively, while those of PFNA-II were 0.61 N m/° (SD 0.39) and 6.6 N m (SD 6.65), respectively. The displacement of MSN-II in each cycle point was less than that of PFNA-II in cyclic loading test. Significantly higher stiffness and less displacement were detected in the MSN-II group (p < 0.05). CONCLUSION: The biomechanical performance of MSN-II was better than that of PFNA-II, suggesting that MSN-II may provide more effective mechanical support in the treatment of unstable intertrochanteric fractures. Cite this article: Bone Joint Res 2020;9(12):840-847.

4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(12): 1344-1348, 2020 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-33306818

RESUMO

OBJECTIVE: To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in three fetuses. METHODS: The three fetuses were predicted to have carried chromosomal abnormalities by non-invasive prenatal testing (NIPT). G-banding chromosomal karyotyping analysis were carried out on amniotic fluid samples of the fetuses and peripheral blood samples from their parents. Single nucleotide polymorphism array (SNP-array) was used to determine the origin, size and genetic effect of sSMCs. RESULTS: In fetus 1, SNP array has detected two microduplications respectively at 4p16.3p15.2 (24.7 Mb) and 18p11.32q11.2 (20.5 Mb) which, as verified by fluorescence in situ hybridization (FISH), have derived from a balanced 46,XY,t(4;18)(p15.2q11.2) translocation carried by its father. Fetus 2 has carried a de novo microduplication of 15q11.2-q13.3 (9.7 Mb). The sequence of SMC in fetus 3 has derived from 21q11.2-q21.1 (8.3 Mb), which was inherited from its mother. CONCLUSION: Both NIPT and SNP-array are highly accurate for the detection of sSMC. SNP-array can delineate the origin and size of abnormal chromosomes, which in turn can help with clarification of sSMC-related genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.

5.
J Ethnopharmacol ; 269: 113736, 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33359917

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Pain is an unpleasant sensory and emotional experience, often accompanied by the occurrence of a variety of diseases. More than 800 kinds of traditional Chinese medicines (TCM) has now been reported for pain relief and several monomers have been developed into novel analgesic drugs. Bupleurum chinense and Angelica biserrata were representatives of the TCM that are currently available for the treatment of pain. AIM OF THE STUDY: The study aims to detect the potential analgesic activity of each monomer of Bupleurum chinense and Angelica biserrata and to explore whether Nav1.7 is one of the targets for its analgesic activity. MATERIALS AND METHODS: In this study, five monomers from Bupleurum chinense (Saikosaponin A, Saikosaponin B1, Saikosaponin B2, Saikosaponin C, Saikosaponin D) and five monomers from the Angelica biserrata (Osthole, Xanthotoxin, Imperatorin, Isoimperatorin, Psoralen) were examined by whole-cell patch-clamp on Nav1.7, which was closely associated with pain. Classical mouse pain models were also used to further verify the analgesic activity in vivo. RESULTS: The results showed that monomers of Saikosaponins and Angelica biserrata all inhibited the peak currents of Nav1.7, indicating that Nav1.7 might be involved in the analgesic mechanism of Saikosaponins and Angelica biserrata. Among them, Saikosaponin A and Imperatorin showed the strongest inhibitory effect on Nav1.7. Furthermore, both Saikosaponin A and Imperatorin showed inhibitory effects on thermal pain and formalin-induced pain in phase II in vivo. CONCLUSION: The results provide valuable information for future studies on the potential of TCM in alleviating pain.

6.
Sci Total Environ ; : 143706, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33250237

RESUMO

Yellow River Delta (YRD) is one of the youngest delta with complex hydrological and biological connectivity in the world, where offers habitats to the famous waterfowls in the Eastern Asia. Meanwhile, one specific ecological restoration project named as the "Wuwanmu" and followed by the "Shiwanmu" within the National Nature Reserve of the Yellow River Delta (NNRYRD) complicated the hydrological and biological connectivity. How to quantitatively evaluate the extent of coastal wetland affected by the project will be a difficult problem. Hence the authors presented three innovative models of the Marine Connectivity Change Index (MCCI), the Coupling Index of Hydro-biological Connectivity (CIHBC), and the Assessment Index of Suitability on Bird Habitats (AISBH). After the project, the habitat of Phragmites australis has been restored effectively with the increased area of 24.59%, while the habitat of Suaeda salsa as the native species lost largely with decreased area of 84.62%. And the tidal channel having been cut off by the project resulted in isolating the buildup restoration area from seawater, and reshaping completely the plant habitat environment. So the hydrological and biological connectivity has been changed largely with the 47.79% decreased MCCI area and the 16.3% decreased zero-valued CIHBC area. However the AISBH non-zero-valued area increased 10.7%, and with the hidden worry of the decreased Grallatores number. From the connectivity prospective, three models presented a significant methodology to evaluate the complex impact on the estuary wetland habitat caused by the restoration project. In the long run, the ecological impacts should be highlighted to the change of tidal channel and the corresponding tidal issues, and the continuous and big loss of native plant spices such as S. salsa. The further study needs to explore the longer-term assessment of the ecological restoration project and its multiple effect in the future.

7.
J Chem Phys ; 153(16): 164119, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33138388

RESUMO

Amorphous alumina (a-AlOx), which plays important roles in several technological fields, shows a wide variation of density and composition. However, their influences on the properties of a-AlOx have rarely been investigated from a theoretical perspective. In this study, high-dimensional neural network potentials were constructed to generate a series of atomic structures of a-AlOx with different densities (2.6 g/cm3-3.3 g/cm3) and O/Al ratios (1.0-1.75). The structural, vibrational, mechanical, and thermal properties of the a-AlOx models were investigated, as well as the Li and Cu diffusion behavior in the models. The results showed that density and composition had different degrees of effects on the different properties. The structural and vibrational properties were strongly affected by composition, whereas the mechanical properties were mainly determined by density. The thermal conductivity was affected by both the density and composition of a-AlOx. However, the effects on the Li and Cu diffusion behavior were relatively unclear.

8.
Asian Pac Isl Nurs J ; 5(2): 55-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33043134

RESUMO

Objectives: The purpose of this study was to explore the characteristics of hardcore smokers who were previously hospitalized. Study design: A descriptive qualitative design was used to investigate a sample of 29 male Taiwanese smokers. Methods: Male hardcore smokers were recruited at a hospital in southern Taiwan and their smoking behaviors and attitudes were explored in semistructured interviews. Inclusion criteria were: (1) smoking at least weekly or daily during the past year, (2) 100 cigarettes during the lifetime, (3) persistent smoking, or (4) at least one hospitalization. Audio-recorded interview data were analyzed using content categorization of the responses. Results: Four main themes emerged to describe characteristics of Taiwanese hardcore smokers: (1) physiological and psychological dependence, (2) no motivation to quit despite knowledge of negative health consequences, (3) social interaction and cultural norms, and (4) negative attitudes toward, but compliance with, smoking-free policies. Conclusions: The results can inform public health nurses of characteristics of Taiwanese hardcore smokers, which in turn may develop effective smoking cessation program to increase smoking cessation rate among Taiwanese hardcore smokers.

9.
J Exp Clin Cancer Res ; 39(1): 222, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087136

RESUMO

BACKGROUND: Radioresistance is the major obstacle in radiation therapy (RT) for hepatocellular carcinoma (HCC). Dysregulation of DNA damage response (DDR), which includes DNA repair and cell cycle checkpoints activation, leads to radioresistance and limits radiotherapy efficacy in HCC patients. However, the underlying mechanism have not been clearly understood. METHODS: We obtained 7 pairs of HCC tissues and corresponding non-tumor tissues, and UBE2T was identified as one of the most upregulated genes. The radioresistant role of UBE2T was examined by colony formation assays in vitro and xenograft tumor models in vivo. Comet assay, cell cycle flow cytometry and γH2AX foci measurement were used to investigate the mechanism by which UBE2T mediating DDR. Chromatin fractionation and immunofluorescence staining were used to assess cell cycle checkpoint kinase 1(CHK1) activation. Finally, we analyzed clinical data from HCC patients to verify the function of UBE2T. RESULTS: Here, we found that ubiquitin-conjugating enzyme E2T (UBE2T) was upregulated in HCC tissues, and the HCC patients with higher UBE2T levels exhibited poorer outcomes. Functional studies indicated that UBE2T increased HCC radioresistance in vitro and in vivo. Mechanistically, UBE2T-RNF8, was identified as the E2-E3 pair, physically bonded with and monoubiquitinated histone variant H2AX/γH2AX upon radiation exposure. UBE2T-regulated H2AX/γH2AX monoubiquitination facilitated phosphorylation of CHK1 for activation and CHK1 release from the chromatin to cytosol for degradation. The interruption of UBE2T-mediated monoubiquitination on H2AX/γH2AX, including E2-enzyme-deficient mutation (C86A) of UBE2T and monoubiquitination-site-deficient mutation (K119/120R) of H2AX, cannot effectively activate CHK1. Moreover, genetical and pharmacological inhibition of CHK1 impaired the radioresistant role of UBE2T in HCC. Furthermore, clinical data suggested that the HCC patients with higher UBE2T levels exhibited worse response to radiotherapy. CONCLUSION: Our results revealed a novel role of UBE2T-mediated H2AX/γH2AX monoubiquitination on facilitating cell cycle arrest activation to provide sufficient time for radiation-induced DNA repair, thus conferring HCC radioresistance. This study indicated that disrupting UBE2T-H2AX-CHK1 pathway maybe a promising potential strategy to overcome HCC radioresistance.

10.
Environ Pollut ; 268(Pt A): 115730, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33007596

RESUMO

In this study, batch and column tests were performed to investigate the co-transport of graphene oxide (GO) nanoparticles and tetracycline in saturated porous media under various solution chemistry conditions. Research indicated that GO and tetracycline had mutual promotion effect on their transport in the porous media under all the tested conditions, which was ascribed to the high adsorption capacity of tetracycline onto GO and the increased electrostatic repulsion as well as their competition for deposition sites on sand surfaces. Interestingly, the mutually promoting function of GO and tetracycline under acidic conditions was greater than that under alkaline conditions, the dominant mechanism was that the increased solution pH decreased the sorption of tetracycline onto GO and weakened the deposition site competition. Furthermore, the mutually promoting effect of GO and tetracycline was Na+ or Ca2+ concentration-dependent. Specially, increased Ca2+ concentration weakened the promoting effect of GO on tetracycline transport but magnified the promoting effect of tetracycline on GO transport. This is because higher Ca2+ concentration could cause a decrease in the adsorption of tetracycline on GO and facilitate more tetracycline molecules to occupy the deposition sites on sand surfaces. Additionally, sodium dodecyl sulfate had enhancement effect on co-transport of GO and tetracycline. Findings from this study clearly indicated that antibiotics and carbon based nanomaterials may transport together under various solution chemistry conditions, and consequently affect their fates in aquatic environments.

11.
J Exp Clin Cancer Res ; 39(1): 229, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121524

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear. METHODS: Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets. RESULTS: We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC. CONCLUSIONS: Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.

12.
Neuropsychiatr Dis Treat ; 16: 2017-2024, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922015

RESUMO

Background: Post-stroke depression (PSD) is one of the most common complications in stroke survivors. But, there are still no objective methods to diagnose PSD. This study aims to identify potential biomarkers for diagnosing PSD in middle-aged stroke survivors. Methods: Middle-aged subjects aged 30 to 59 years (92 PSD patients and 89 stroke survivors without depression) were included in this study. Urinary metabolites were detected by gas chromatography-mass spectrometry (GC-MS). Differential urinary metabolites and potential biomarkers were screened by applying statistical analysis. Results: The different urinary metabolic phenotypes between PSD patients and stroke survivors without depression were identified. A total of 12 differential urinary metabolites were accurately identified by using orthogonal partial least-squares-discriminant analysis. After analyzing those 12 differential urinary metabolites by step-wise logistic regression analysis, only seven metabolites (palmitic acid, hydroxylamine, myristic acid, glyceric acid, lactic acid, tyrosine and azelaic acid) were finally selected as potential biomarkers for diagnosing PSD in middle-aged stroke survivors. A panel consisting of these potential biomarkers could effectively diagnose middle-aged PSD patients. Conclusion: Urinary metabolic profiles were different between middle-aged PSD patients and stroke survivors without depression. Our results would be helpful in future for developing an objective method to diagnose PSD in middle-aged stroke survivors.

13.
Opt Express ; 28(18): 25730-25749, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32906858

RESUMO

An efficient radiative transfer model (ERTM) is developed to simulate thermal infrared brightness temperatures observed by the Advanced Himawari Imager (AHI) in this study. The ERTM contains an alternate mapping correlated k-distribution (AMCKD) scheme, a parameterization for cloud optical property, and a rapid infrared radiative transfer scheme. The AMCKD is employed to calculate the gaseous absorption in the inhomogeneous thermodynamic atmosphere. The optical properties of clouds are parameterized by the effective length for ice clouds based on the Voronoi model, and by the effective radius for water clouds based on the Lorenz-Mie theory. The adding method of four-stream discrete ordinates method (4DDA) is extended to be able to calculate the thermal infrared radiative intensity varying with the zenith angle in ERTM. The efficiency and accuracy of ERTM are evaluated by comparing with the benchmark model which is composed of discrete ordinate radiative transfer (DISORT) and line-by-line radiative transfer model (LBLRTM). Under the standard atmospheric profiles, the root mean square error (RMSE) of simulated brightness temperatures reaches a maximum of 0.21K at the B16 (13.28 µm) channel of AHI. The computational efficiency of ERTM is approximately five orders of magnitude higher than that of the benchmark model. Moreover, the simulated brightness temperatures by ERTM are highly consistent with the rigorous results and AHI observations in the application to the Typhoon Mujigae case.

14.
J Physiol Biochem ; 76(4): 587-598, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32875543

RESUMO

Chronic fructose consumption and vitamin D deficiency (VDD) diet have been linked to the pandemic of metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD). The metabolic mechanisms remain unclear. This study is to explore metabolic changes of mice fed with high fructose syrup and VDD diet in the biogenesis of MetS and NAFLD. C57BL/6J mice were treated with four conditions for 28 weeks: control (standard chow and sterile water), fructose drinking (FD, standard chow and 20 g/100 mL fructose in drinking water), VDD (standard chow with VD depleted and sterile water), and FD+VDD. Metabolites in the serum and liver of mice were analyzed by gas chromatography-mass spectrometry combined with trimethylsilyl derivatization. The histological results indicated that one-hit from long-term fructose drinking led to mild MetS, and a combination with VDD diet induced hepatic steatosis, inflammatory lesion, and interstitial fibrosis in mice, showing significant nonalcoholic steatohepatitis features. Metabolomics analysis showed significant changes in amino acids and short-chain organic acids in response to fructose drinking. VDD diet led to significant increase of hepatic fatty acids, which was consistent with the hepatic morphology of fat deposition. This work demonstrated a concert effect of FD and VDD in promoting MetS and NAFLD through changing in vivo metabolism and signaling pathways. And metabolomics analysis could provide early warnings for the biogenesis of MetS and NAFLD. Importantly, vitamin D supplementation in the diet can balance the metabolic disorders caused by excessive fructose intake.

15.
Theranostics ; 10(23): 10434-10447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32929358

RESUMO

Background: Tumor necrosis factor receptor 1 (TNFR1) signaling plays a pleiotropic role in the development of hepatocellular carcinoma (HCC). The formation of TNFR1-complex I supports cell survival while TNFR1-complex II leads to apoptosis, and the underlying mechanisms of the transformation of these TNFR1 complexes in HCC remain poorly defined. Methods: The interaction protein of TNFR1 was identified by GST pulldown assay, immunoprecipitation and mass spectrometry. In vitro and in vivo assay were performed to explore the biological features and mechanisms underlying the regulation of TNFR1 signals by histidine-rich glycoprotein (HRG). Data from the public databases and HCC samples were utilized to analyze the expression and clinical relevance of HRG. Results: HRG directly interacted with TNFR1 and stabilized TNFR1 protein by decreasing the Lys(K)-48 ubiquitination mediated-degradation. The formation of TNFR1-complex II was prompted by HRG overexpression via upregulating Lys(K)-63 ubiquitination of TNFR1. Besides, overexpression of HRG suppressed expression of pro-survival genes by impairing the activation of NF-κB signaling in the presence of TNFR1. Moreover, downregulation of HRG was a result of feedback inhibition of NF-κB activation in HCC. In line with the pro-apoptotic switch of TNFR1 signaling after HRG induction, overexpression of HRG inhibited cell proliferation and increased apoptosis in HCC. Conclusions: Our findings illustrate a crucial role for HRG in suppressing HCC via inclining TNFR1 to a pro-apoptotic cellular phenotype. Restoring HRG expression in HCC tissues might be a promising pharmacological approach to blocking tumor progression by shifting cellular fate from cell survival to apoptosis.

16.
Drug Des Devel Ther ; 14: 3663-3672, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982173

RESUMO

Purpose: To explore the exact mechanism through which emodin down-regulates the migration and invasion abilities of endometrial stromal cells. Moreover, to explore the theoretical basis of emodin in the treatment of endometriosis. Patients and Methods: Endometriosis endometrial stromal cells (EESs) were cultured from 15 women with endometriosis and control endometrial stromal cells (CESs) were cultured from 12 women without endometriosis. The levels of proteins were evaluated by Western blot. The migration and invasion abilities of cells were detected by transwell assays. Results: The abilities of migration and invasion of EESs were much stronger than those of CESs. After treated with emodin, the migration and invasion abilities of EESs and CESs were significantly down-regulated, and the levels of integrin-linked kinase (ILK) and p-GSK-3ß were statistically down-regulated in EESs. Besides that, the expression of keratin was up-regulated while the expression of vimentin, ß-catenin and slug were all down-regulated by emodin in a dose- and time-dependent manner. Silencing of ILK gene in EESs also achieved the above effects, which were strengthened by emodin. Conversely, exogenous expression of ILK in CESs increased the expression of p-GSK-3ß, which were abrogated by emodin. Furthermore, SB216763 increased migration and invasion abilities of CESs by facilitating the epithelial-mesenchymal transition (EMT) through up-regulating levels of p-GSK-3ß, ß-catenin and slug, which were also abrogated by emodin. Conclusion: Emodin inhibits the migration and invasion abilities of human endometrial stromal cells by reversing the EMT via ILK/GSK-3ß pathway. So, emodin may be considered as a promising targeted therapy for endometriosis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32938225

RESUMO

Endogenous hydrogen sulfide (H2S) affects cholesterol homeostasis and liver X receptor α (LXRα) expression. However, whether low density lipoprotein (LDL) receptor (LDLR), a key player in cholesterol homeostasis, is regulated by exogenous H2S through LXRα signaling has not been determined. We investigated the effects of sodium hydrosulfide (NaHS, H2S donor) on LDLR expression in the presence or absence of LXR agonists, T0901317 or GW3965 in HepG2 cells. We found that H2S strongly accumulated LDLR precursor in the presence of T0901317. Hence LDLR transcription and the genes involved in LDLR precursor maturation and degradation were studied. T0901317 increased the LDLR mRNA level, while H2S didn't affect LDLR transcription. H2S had no significant effect on the expression of LXRα and inducible degrader of LDLR (IDOL). H2S and T0901317 altered mRNA levels of several enzymes for N- and O-glycosylation and endoplasmic reticulum (ER) chaperones assisting LDLR maturation, but didn't affect their protein levels. H2S decreased proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels and its mRNA level elevated by T0901317. T0901317 with PCSK9 siRNA also accumulated LDLR precursor as did T0901317 with H2S. High glucose increased PCSK9 protein levels and attenuated LDLR precursor accumulation induced by T0901317 with H2S. Taken together, H2S accumulates LDLR precursor by downregulating PCSK9 expression but not through the LXRα-IDOL pathway, LDLR transcriptional activation or dysfunction of glycosylation enzymes and ER chaperones. These results also indicate that PCSK9 plays an important role in LDLR maturation in addition to its well-known effect on the degradation of LDLR mature form.

18.
Chemosphere ; 261: 127813, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32768750

RESUMO

Fish play an important role as a primary eco-toxicity test organism in environmental hazard assessment. Toxicity data of native species are often sought for use in the derivation of water quality criteria (WQC). The Chinese medaka, Oryzias sinensis, is an endemic species of China. The acute toxicity of 6 chemicals on O. sinensis was tested in this work, and toxicity effect of 10 chemicals to O. sinensis was compared with 4 commonly used species globally. A total of 9 robust interspecies correlation estimation (ICE) models using O. sinensis as the surrogate species were constructed and used to derive predicted no effect concentration and hazardous concentrations of 5% species (HC5) values based on species sensitivity distribution. Results showed that the 96 h median lethal concentration of Hg2+, Cr6+, linear alkylbenzene sulfonates, triclosan, 3,4-dchloroaniline, sodium chloride to O. sinensis were 0.29, 50, 6.0, 0.63, 9.2 and 14,400 mg/L, respectively. The sensitivity of O. sinensis and other 4 testing organisms were statistically indistinguishable (P > 0.05). No significant difference among HC5-ICE, HC5-measured and HC5 from published literatures was identified. All results indicated the O. sinensis is a potential model organism in the application of eco-toxicity and WQC in China and other Asian countries.


Assuntos
Oryzias/fisiologia , Testes de Toxicidade , Poluentes Químicos da Água/toxicidade , Animais , China , Monitoramento Ambiental/métodos , Mercúrio , Especificidade da Espécie , Poluentes Químicos da Água/análise , Qualidade da Água
19.
Onco Targets Ther ; 13: 5177-5190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606738

RESUMO

Purpose: Phosphatidylinositol 3-kinase (PI3K) plays an important role in tumorigenesis by cross-talking with several signaling pathways. p55PIK is a unique regulatory subunit of PI3K and contains an extra 24-residue N-terminal domain (N24). This study aimed to explore the interaction of p55PIK with p53 and the role of p55PIK in regulating p53-dependent apoptosis in cancer cells. Materials and Methods: The expression of p55PIK was detected in cancer cells, and the interaction of p55PIK with p53 was examined by immunoprecipitation and pull-down assay. The expression of p53-dependent apoptosis-related genes was detected by PCR. Results: N24 domain of p55PIK interacted with DNA-specific binding domain (DBD) of p53. The increase or decrease of p55PIK expression led to the change of the expression of p53 and p53-regulated genes in cancer cells. Moreover, N24 peptide led to the change of the expression of p53-regulated genes. Moreover, a membrane-permeable N24 peptide enhanced p53-dependent apoptosis induced by methyl methanesulfonate. Conclusion: Our results reveal a novel mechanism that regulates p53-dependent apoptosis in cancer cells via p55PIK-p53 interaction.

20.
Front Neurol ; 11: 284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477232

RESUMO

Stiff limb syndrome (SLS) is a rare autoimmune-related central nervous system disorder, resulting in stiffness and spasms of limbs since onset with rare involvement of the truncal muscles. However, SLS patients will gain notable effects by appropriate therapy focusing on symptomatic treatment and immunotherapy. We reported on a 55-year-old female who showed typical painful spasms in both lower limbs and abduction of the right eyeball that partially responded to low-dose diazepam and had high-titer anti-glutamic acid decarboxylase (anti-GAD) antibody. Electromyography (EMG) only showed continuous motor unit activity (CMUA) in the anterior tibialis and right triceps. Eventually, our patient was diagnosed with SLS and treated with intravenous immunoglobulin (IVIG) and glucocorticoid combined simultaneously. She obtained notable effects. We also review and summarize the current literature on clinical characteristics, coexisting disease, treatment, and outcome of 40 patients with SLS. We hope that this report will provide a basis for further understanding of SLS and promote the formation of more advanced diagnosis and treatment processes.

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