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Understanding the dynamic change in abundance of both fecal and opportunistic waterborne pathogens in urban surface water under different abiotic and biotic factors helps the prediction of microbiological water quality and protection of public health during recreational activities, such as swimming. However, a comprehensive understanding of the interaction among various factors on pathogen behavior in surface water is missing. In this study, the effect of salinity, light, and temperature and the presence of indigenous microbiota, on the decay/persistence of Escherichia coli and Pseudomonas aeruginosa in Rhine River water were tested during 7 days of incubation with varying salinity (0.4, 5.4, 9.4, and 15.4 ppt), with light under a light/dark regime (light/dark) and without light (dark), temperature (3, 12, and 20 °C), and presence/absence of indigenous microbiota. The results demonstrated that light, indigenous microbiota, and temperature significantly impacted the decay of E. coli. Moreover, a significant (p<0.01) four-factor interactive impact of these four environmental conditions on E. coli decay was observed. However, for P. aeruginosa, temperature and indigenous microbiota were two determinate factors on the decay or growth. A significant three-factor interactive impact between indigenous microbiota, temperature, and salinity (p<0.01); indigenous microbiota, light, and temperature (p<0.01); and light, temperature, and salinity (p<0.05) on the decay of P. aeruginosa was found. Due to these interactive effects, caution should be taken when predicting decay/persistence of E. coli and P. aeruginosa in surface water based on a single environmental condition. In addition, the different response of E. coli and P. aeruginosa to the environmental conditions highlights that E. coli monitoring alone underestimates health risks of surface water by non-fecal opportunistic pathogens, such as P. aeruginosa. KEY POINTS: Abiotic and biotic factors interactively affect decay of E. coli and P. aeruginosa E.coli and P.aeruginosa behave significantly different under the given conditions Only E. coli as an indicator underestimates the microbiological water quality.
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Escherichia coli , Pseudomonas aeruginosa , Rios , Fezes , Água DoceRESUMO
Diabetic retinopathy (DR) is a leading cause of vision impairment in the working-age population worldwide. Various modes of photoreceptor cell death contribute to the development of DR, including apoptosis and autophagy. However, whether ferroptosis is involved in the pathogenesis of photoreceptor degeneration in DR is still unclear. High-glucose (HG)-stimulated 661W cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. The levels of intracellular iron, glutathione (GSH), reactive oxygen species (ROS), lipid peroxidation (MDA), and ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, FTH1, and NCOA4) were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. Our data showed the levels of iron, ROS, and MDA were enhanced and GSH concentration was reduced in HG-induced 661W cells and diabetic retinas. The expression of GPX4 and SLC7A11 was downregulated, while the expression of ACSL4, FTH1, and NCOA4 was upregulated in the 661W cells cultured under HG conditions and in the photoreceptor cells in diabetic mice. Furthermore, the administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1) obviously alleviated ferroptosis-related changes in HG-cultured 661W cells and in retinal photoreceptor cells in diabetic mice. Taken together, our findings suggest that ferroptosis is involved in photoreceptor degeneration in the development of the early stages of DR.
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3,4-Metilenodioxianfetamina , Diabetes Mellitus Experimental , Retinopatia Diabética , Ferroptose , Animais , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Espécies Reativas de Oxigênio , Retinopatia Diabética/tratamento farmacológico , Glutationa , Ferro , Fatores de TranscriçãoRESUMO
This work aimed to detect the vegetation coverage and evaluate the benefits of afforestation and ecological protection. Unmanned aerial vehicle (UAV) aerial survey was adopted to obtain the images of tailings area at Ma'anshan near the Dianchi Lake estuary, so as to construct a high-resolution Digital Orthophoto Map (DOM) and high-density Dense Image Matching (DIM) point cloud. Firstly, the optimal scale was selected for segmentation by considering the terrain. Secondly, the visible-band difference vegetation index (VDVI) of the classified vegetation information of the tail mining area was determined from the index gray histogram, ground class error analysis, and the qualitative and quantitative analysis of the bimodal index. Then, the vegetation information was extracted by combining the random forest (RF) classification algorithm. Finally, the extracted two-dimensional (2D) vegetation information was mapped to the three-dimensional (3D) point cloud, and the redundant data was eliminated. Fractional vegetation cover (FVC) was counted in the way of surface to point and human-machine combination. The experimental results showed that the vegetation information extracted from the 2D image was mapped to the 3D point cloud in the form of surface to point, and the redundant bare ground information was eliminated. The statistical FVC was 36.06%. The field survey suggested that the vegetation information in the turf dam area adjacent to the open phosphate deposit accumulation area research area was sparse. Relevant measures should be taken in the subsequent mining to avoid ecological damage caused by expanded phosphate mining. In general, applying UAV measurement technology and related 2D and 3D products to detect the vegetation coverage in an open phosphate mine area was of practical significance and unique technical advantages.
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Lagos , Tecnologia de Sensoriamento Remoto , Humanos , Mineração , FosfatosRESUMO
Individual tree structural parameters are vital for precision silviculture in planted forests. This study used near-field LiDAR (light detection and ranging) data (i.e., unmanned aerial vehicle laser scanning (ULS) and ground backpack laser scanning (BLS)) to extract individual tree structural parameters and fit volume models in subtropical planted forests in southeastern China. To do this, firstly, the tree height was acquired from ULS data and the diameter at breast height (DBH) was acquired from BLS data by using individual tree segmentation algorithms. Secondly, point clouds of the complete forest canopy were obtained through the combination of ULS and BLS data. Finally, five tree taper models were fitted using the LiDAR-extracted structural parameters of each tree, and then the optimal taper model was selected. Moreover, standard volume models were used to calculate the stand volume; then, standing timber volume tables were created for dawn redwood and poplar. The extraction of individual tree structural parameters exhibited good performance. The volume model had a good performance in calculating the standing volume for dawn redwood and poplar. Our results demonstrate that near-field LiDAR has a strong capability of extracting tree structural parameters and creating volume tables for subtropical planted forests.
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Árvores , Dispositivos Aéreos não Tripulados , China , Florestas , LasersRESUMO
Unmanned Aerial Vehicles (UAVs) are a novel technology for landform investigations, monitoring, as well as evolution analyses of long-term repeated observation. However, impacted by the sophisticated topographic environment, fluctuating terrain and incomplete field observations, significant differences have been found between 3D measurement accuracy and the Digital Surface Model (DSM). In this study, the DJI Phantom 4 RTK UAV was adopted to capture images of complex pit-rim landforms with significant elevation undulations. A repeated observation data acquisition scheme was proposed for a small amount of oblique-view imaging, while an ortho-view observation was conducted. Subsequently, the 3D scenes and DSMs were formed by employing Structure from Motion (SfM) and Multi-View Stereo (MVS) algorithms. Moreover, a comparison and 3D measurement accuracy analysis were conducted based on the internal and external precision by exploiting checkpoint and DSM of Difference (DoD) error analysis methods. As indicated by the results, the 3D scene plane for two imaging types could reach an accuracy of centimeters, whereas the elevation accuracy of the orthophoto dataset alone could only reach the decimeters (0.3049 m). However, only 6.30% of the total image number of oblique images was required to improve the elevation accuracy by one order of magnitude (0.0942 m). (2) An insignificant variation in internal accuracy was reported in oblique imaging-assisted datasets. In particular, SfM-MVS technology exhibited high reproducibility for repeated observations. By changing the number and position of oblique images, the external precision was able to increase effectively, the elevation error distribution was improved to become more concentrated and stable. Accordingly, a repeated observation method only including a few oblique images has been proposed and demonstrated in this study, which could optimize the elevation and improve the accuracy. The research results could provide practical and effective technology reference strategies for geomorphological surveys and repeated observation analyses in sophisticated mountain environments.
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Retinopathy of prematurity (ROP) is an important cause of visual loss in children born prematurely. Although the involvement of inflammation in the development of ROP is gaining increasing attention, the role of IL-17A in ROP progress remains unclear. The aim of this study was to assess the levels of IL-17A production in the mice model of oxygen-induced retinopathy (OIR) and elucidate its potential roles. Wild-type (WT) and IL-17A knockout (IL-17A-/-) mice were exposed to 75% O2 from postnatal day 7 (P7) to P12. Age-matched controls were maintained in room air. Primary Müller cells isolated from WT or IL-17A-/- mice retina were co-cultured with 661W cells and exposed to hypoxic conditions. Western blotting and immunofluorescent staining were used to assess the expression of target protein. Apoptosis in OIR retinal sections and 661W cells was detected by TUNEL staining. Results turned out that IL-17A expression was increased and reached a peak at P22 in OIR retina and at 8â¯h in hypoxic-cultured Müller cells. IL-17A knockout decreased the expression of glial fibrillary acidic protein (GFAP) and mature neurotrophin-3 (NT-3) in retina of OIR mice as well as hypoxic-cultured Müller cells. The NT-3 release induced by IL-17 was prevented by an ERK-specific inhibitor. In addition, more apoptosis cells and higher levels of Bax and cleaved caspase-3 was detected in the retina tissues of IL-17A-/- OIR and the 661W cells co-cultured with IL-17A-/- Müller cells. Taken together, our findings suggest that Müller cell was the potential source of IL-17A under the hypoxic conditions. Modulation of the IL-17A/ERK/NT-3 pathway exerts anti-apoptotic effect on photoreceptor cell and may be a novel therapeutic strategy for ROP.
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Apoptose , Modelos Animais de Doenças , Células Ependimogliais/metabolismo , Interleucina-17/fisiologia , Oxigênio/toxicidade , Células Fotorreceptoras de Vertebrados/patologia , Retinopatia da Prematuridade/metabolismo , Animais , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Proteína Glial Fibrilar Ácida/metabolismo , Hipóxia/metabolismo , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Crescimento Neural/metabolismo , Retinopatia da Prematuridade/induzido quimicamente , Retinopatia da Prematuridade/patologiaRESUMO
BACKGROUND: To report a case series in which a modified technique was used to remove retained submacular perfluorocarbon liquid (PFCL) secondary to vitreoretinal surgery for rhegmatogenous retinal detachment. CASE PRESENTATION: Four patients who had undergone pars plana vitrectomy for rhegmatogenous retinal detachment were further treated with surgical intervention because of retained submacular PFCL. With a three-port pars plana approach, after the internal limiting membrane peeling with indocyanine green staining, a 38-gauge flexible cannula was used to aspirate the submacular perfluorocarbon bubble, followed by fluid-air exchange and air injection into vitreous cavity. Submacular perfluorocarbon liquid was removed successfully and visual acuity had an improvement in all cases. CONCLUSION: The surgical removal of retained submacular PFCL using a 38-gauge flexible cannula combined with internal limiting membrane peeling and intravitreal air tamponade may provide anatomical and visual satisfactory outcomes.
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Cateterismo/instrumentação , Tamponamento Interno/métodos , Membrana Epirretiniana/cirurgia , Fluorocarbonos , Complicações Pós-Operatórias/cirurgia , Vitrectomia/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/cirurgia , Sucção/métodos , Vitrectomia/métodosRESUMO
Many bacterial strains have been demonstrated to biodegrade lignin for contaminant removal or resource regeneration. The goal of this study was to investigate the biodegradation amount and associated pathways of three lignin monomers, vanillic, p-coumaric, and syringic acid by strain Sphingobacterium sp. HY-H. Vanillic, p-coumaric, and syringic acid degradation with strain HY-H was estimated as 88.71, 76.67, and 72.78%, respectively, after 96 h. Correspondingly, the same three monomers were associated with a COD removal efficiency of 87.30, 55.17, and 67.23%, and a TOC removal efficiency of 82.14, 61.03, and 43.86%. The results of GC-MS, HPLC, FTIR, and enzyme activities show that guaiacol and o-dihydroxybenzene are key intermediate metabolites of the vanillic acid and syringic acid degradation. p-Hydroxybenzoic acid is an important intermediate metabolite for p-coumaric and syringic acid degradation. LiP and MnP play an important role in the degradation of lignin monomers and their intermediate metabolites. One possible pathway is that strain HY-H degrades lignin monomers into guaiacol (through decarboxylic and demethoxy reaction) or p-hydroxybenzoic acid (through side-chain oxidation); then guaiacol demethylates to o-dihydroxybenzene. The p-hydroxybenzoic acid and o-dihydroxybenzene are futher through ring cleavage reaction to form small molecule acids (butyric, valproic, oxalic acid, and propionic acid) and alcohols (ethanol and ethanediol), then these acids and alcohols are finally decomposed into CO2 and H2O through the tricarboxylic acid cycle. If properly optimized and controlled, the strain HY-H may play a role in breaking down lignin-related compounds for biofuel and chemical production.
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Ácidos Cumáricos/metabolismo , Ácido Gálico/análogos & derivados , Lignina/química , Sphingobacterium/metabolismo , Ácido Vanílico/metabolismo , Biodegradação Ambiental , Ácidos Cumáricos/química , Ácido Gálico/química , Ácido Gálico/metabolismo , Lignina/metabolismo , Redes e Vias Metabólicas , Oxirredução , Ácido Vanílico/químicaRESUMO
Hedyotis hedyotidea has been traditionally used for the treatment of arthritis, cold, cough, gastro-enteritis, headstroke, etc. But few studies have screened the active compounds from extracts of H. hedyotidea. In this study, the structure of the chemical constituents from stems of H. hedyotidea were determined and the immunosuppressive activity of the compounds was evaluated. The compounds were separated and purified with silica gel, gel column chromatographies and preparative HPLC, and their structures were identified by spectral methods such as MS and NMR. Eleven compounds were obtained and identified as(6S,9S) -vomifoliol (1), betulonic acid (2), betulinic acid (3), betulin(4), 3-epi-betulinic acid (5), ursolic acid (6), ß-sitosterol (7), stigmast-4-en-3-one (8), 7ß-hydroxysitosterol (9), (3ß,7ß) -7-methoxystigmast-5-en-3-ol (10) and morindacin (11). This is the first report of compounds 1, 2, 4, 8, 9, 10 and 11 from H. hedyotidea. Compounds 1, 2 and 8-11 were firstly isolated from the genus Hedyotis, and compounds 9 and 10 were isolated from the family Rubiaceae for the first time. The immunosuppressive activity of these compounds was tested using the lymphocyte transsormationtest. Compounds 4, 6 and 9 showed significant immunosuppressive activity.
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Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hedyotis/química , Imunossupressores/química , Imunossupressores/farmacologia , Caules de Planta/química , Animais , Medicamentos de Ervas Chinesas/isolamento & purificação , Imunossupressores/isolamento & purificação , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Estrutura MolecularRESUMO
A novel palladium-catalyzed oxidative double carbonylation of o-iodoanilines for the synthesis of isatoic anhydrides has been developed. The reaction employs readily available o-iodoanilines as the starting materials and proceeds under mild conditions. For extension, palladium-catalyzed oxidative carbonylation of anthranilic acids was developed for the synthesis of substituted isatoic anhydrides in high to excellent yields.
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We explored the effect of inhibition of thioredoxin interacting protein (Txnip) on neuroprotection in Müller cells under high glucose. Wild-type (WT) and Txnip knockout (Txnip-/-) mice were used to establish a streptozotocin (STZ)-induced diabetes model and a Müller cells high glucose model. We detected BDNF expression and PI3K/AKT/CREB pathway activation levels in the retina and Müller cells of each group in vivo and in vitro experiments. The Txnip-/- STZ group showed higher expression of BDNF and phosphorylation of PI3K/AKT/CREB in retina, and less retinal photoreceptor apoptosis was observed in Txnip-/- diabetic group than in WT. After using an inhibitor of PI3K signaling pathway, BDNF expression was reduced; In vitro co-cultured with Müller cells in different groups, 661 W cells showed different situations, Txnip-/- Müller cells maximum downregulated Cleaved-caspase 3 expression in 661 W, accompanied by an increase in Bcl-2/Bax ratio. These findings indicate that inhibiting endogenous Txnip in mouse Müller cells can promote their expression and secretion of BDNF, thereby reducing HG induced photoreceptor apoptosis and having important neuroprotective effects on DR. The regulation of BDNF expression by Txnip may be achieved by activating the PI3K/AKT/CREB pathway. This study suggests that regulating Txnip may be a potential target for DR treatment.
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Apoptose , Proteínas de Transporte , Diabetes Mellitus Experimental , Células Ependimogliais , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Células Ependimogliais/metabolismo , Células Ependimogliais/efeitos dos fármacos , Células Ependimogliais/patologia , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Camundongos , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Knockout , Células Fotorreceptoras/metabolismo , Células Fotorreceptoras/efeitos dos fármacos , Células Fotorreceptoras/patologia , Técnicas de Silenciamento de Genes , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Tiorredoxinas/metabolismo , Tiorredoxinas/genética , Masculino , Retinopatia Diabética/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patologia , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
One new lignan (7S,8R,7'R,8'R)-7-(3,4-methylenedioxyphenyl)-8,8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3',4'-methylenedioxyphenyl)-tetrahydrofuran (1), one new sesquiterpene 2-hydroxy-11,12-dehydrocalamenene (2), one new natural product erythro-1-(3,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane (3), and two known lignans (+)-anwulignan(erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane) (4) and ( - )-zuonin-A (5) were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated by spectroscopic methods. The cytotoxicity of compounds 1 and 2 was assayed.
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Medicamentos de Ervas Chinesas/isolamento & purificação , Lignanas/isolamento & purificação , Schisandra/química , Sesquiterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Furanos , Células HCT116 , Humanos , Lignanas/química , Lignanas/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Caules de Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , EstereoisomerismoRESUMO
OBJECTIVE: To study the chemical constituents from Schisandra glaucescens. METHOD: The chemical constituents were separated and purifed with silica gel, gel column chromatography preparative HPLC, and their structures were identified by such spectral methods as MS and NMR. RESULT: Twelve compounds were separated from petroleum ether fractions, and identified as t-cadinol (1), alpha-cadinol (2), torreyol (3), (+)-ent-epicubenol (4), ent-T-muurolol (5), (-)-15-hydroxycalamenene (6), (-)-cubebol (7), 4-epi-cubebol (8), caryophyllenol-I (9), caryophyllenol-II (10), oxyphyllenodiols A (11), caryolane-1,9/3-diol (12). CONCLUSION: Compounds 4, 6-12 were separated from the genus for the first time, while compounds 1-12 were separated from this plant for the first time.
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Medicamentos de Ervas Chinesas/química , Caules de Planta/química , Schisandra/química , Sesquiterpenos/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesquiterpenos/isolamento & purificaçãoRESUMO
Diabetic retinopathy (DR) represents an important microvascular complication of diabetes, which is the top etiology of vision impairment worldwide. Although interleukin (IL)-17A is increasingly implicated in DR development, the underlying cellular mechanisms remain poorly defined. This work aims to evaluate IL-17A levels in the retina of streptozotocin (STZ)-induced diabetic mice and elucidate their potential roles. We found IL-17A was upregulated in diabetic retina after intraperitoneal injection of STZ and high-glucose (HG)-cultured primary Müller cells. IL-17A knockout (IL-17A-/-) downregulated glial fibrillary acidic protein (GFAP) and inhibited the conversion of proneurotrophin-3 (proNT-3) to mature NT-3 in retinal specimens from diabetic mice as well as in Müller cells cultured under HG conditions. Induced apoptosis and upregulated Bax and cleaved caspase-3 were observed in retinal specimens from IL-17A-/- diabetic mice and photoreceptor (661 W) cells after co-culture with IL-17A-/- Müller cells. Moreover, RNA interference-induced gene silencing of tyrosine kinase C receptor (TrkC) in 661 W cells reversed the anti-apoptotic effect of IL-17A under HG conditions. Taken together, our findings suggest that IL-17A/NT-3/TrkC axis regulation suppresses apoptosis in photoreceptor cells, providing a new treatment strategy for DR.
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Diabetes Mellitus Experimental , Retinopatia Diabética , Animais , Apoptose , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/induzido quimicamente , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Modelos Animais de Doenças , Interleucina-17/genética , Camundongos , Células Fotorreceptoras/metabolismo , EstreptozocinaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive carcinoma with genome instability. Long non-coding RNAs (LncRNAs) have been functionally associated with genomic instability in cancers. However, the identification and prognostic value of lncRNAs related to genome instability have not been explored in hepatocellular carcinoma. In this study, we aim to identify a genomic instability-related lncRNA signature for predicting prognosis and the efficacy of immunotherapy in HCC patients. METHODS: According to the somatic mutation and transcript data of 364 patients with HCC, we determined differentially expressed genome instability-related lncRNAs (GInLncRNAs). Gene ontology (GO) enrichment analyses and Kyoto Encyclopedia of genes and genomes enrichment analyses revealed the potential functions of genes co-expressed with those lncRNAs involved in cancer development and immune function. We further determined a genome instability-related lncRNA signature (GInLncSig) through Cox regression analysis and LASSO regression analysis. Thereafter, we performed correlation analyses with mutations, clinical stratification analyses, and survival analyses to evaluate GInLncSig predictive function. Subsequently, we construct a nomogram model for prognostic assessments of patients with HCC. Finally, we performed Immunocytes infiltration analysis, gene set enrichment analysis (ssGSEA) of immunity circle-associated pathways, and T cell-inflamed score to explore GInLncSig's potential value in guiding immunotherapy. RESULTS: We identified 11 independent prognosis-associated GInLncRNAs (AC002511.2, LINC00501, LINC02055, LINC02714, LINC01508, LOC105371967, RP11_96A15.1, RP11_305F18.1, RP11_342M1.3, RP11_432J24.3, U95743.1) to construct a GInLncSig. According to the risk score calculated by GInLncSig, the high-risk group was characterized by a higher somatic mutation count, significantly poorer clinical prognosis, higher T cell-inflamed score, and specific tumor immune infiltration status compared to the low-risk group. Furthermore, we constructed a nomogram model to improve the reliability and clinical utility of predicting the prognosis of patients with HCC. CONCLUSION: Our study established a reliable prognostic prediction signature that could be a tool for prognosis prediction and a promising predictive biomarker of immunotherapy in hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Mutação , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Reprodutibilidade dos Testes , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Neovascularization is a leading cause of visual loss typically associated with diabetic retinopathy (DR) and retinopathy of prematurity (ROP). Interleukin-17A (IL-17A) and endoplasmic reticulum (ER) stress both have been demonstrated to play a proangiogenic role in ischemic retinopathies. However, the relationship between IL-17A and ER stress in retinal neovascularization (RNV) under hypoxic conditions and its underlying mechanisms remain unclear. METHODS: In this study, oxygen-induced retinopathy (OIR) mice model was established and intravitreal injections were conducted. Changes of IL-17A and ER stress markers in retinas and cultured primary bone marrow derived macrophage (BMDM) under normoxic or hypoxic conditions were detected. Western blotting, Real-Time RT-PCR, Immunofluorescence assays were conducted to explore the roles and relationship of IL-17A and ER stress in RNV, as well as its underlying mechanisms. RESULTS: Compared to that in normal controls, IL-17A and ER stress markers were all remarkably increased under hypoxic conditions both in vivo and in vitro. Neutralization or knock out of IL-17A decreased ER stress. ER stress inhibitor 4-phenylbutyrate (4-PBA), attenuated the production of IL-17A, suggesting a positive feedback loop between IL-17A and ER stress. Inhibition of IL-17A or ER stress decreased areas of nonperfusion and neovascularization in OIR retinas. As TXNIP/NLRP3 pathway activation has been demonstrated to be involved in increased retinal vascular permeability of ischemic retinopathy, we observed that TXNIP/NLRP3 pathway mediated in the interaction between IL-17A and ER stress under hypoxic conditions. CONCLUSION: The interplay between IL-17A and ER stress contributes to RNV in macrophages via modulation of TXNIP/NLRP3 signaling pathway under hypoxic conditions. The feedback loops may become an innovative and multiple pharmacological therapeutic target for ischemic retinopathy.
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DNA-stable isotope probing (SIP) with 13C labeled phenanthrene (PHE) as substrate was used to identify specific bacterial degraders during natural attenuation (NA) and bioaugmentation (BA) in petroleum contaminated soil. BA, with the addition of a bacterial suspension mixture named GZ, played a significant role in PHE degradation with a higher PHE removal rate (â¼90%) than that of NA (â¼80%) during the first 3 days, and remarkably altered microbial communities. Of the five strains introduced in BA, only two genera, particularly, Ochrobactrum, Rhodococcus were extensively responsible for PHE-degradation. Six (Bacillus sp., Acinetobacter sp., Xanthomonas sp., Conexibacter sp., Acinetobacter sp. and Staphylococcus sp.) and seven (Ochrobactrum sp., Rhodococcus sp., Alkanindiges sp., Williamsia sp., Sphingobium sp., Gillisia sp. and Massilia sp.) bacteria responsible for PHE degradation were identified in NA and BA treatments, respectively. This study reports for the first time the association of Xanthomonas sp., Williamsia sp., and Gillisia sp. to PHE degradation.
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Petróleo , Fenantrenos , Poluentes do Solo , Biodegradação Ambiental , DNA , Isótopos , Fenantrenos/análise , Solo , Microbiologia do Solo , Poluentes do Solo/análiseRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains dismal. Hence, it is important to identify the diagnostic and prognostic biomarkers for HCC. Urokinase plasminogen activator (uPA), an extracellular matrix (ECM)-degrading protease, plays a pivotal role in the invasion and metastasis of HCC. METHODS: To confirm the clinical significance of uPA in HCC, we explored uPA expression in HCC in The Cancer Genome Atlas (TCGA) database. The expression level of uPA was further verified by quantitative reverse transcription polymerized chain reaction (qRT-PCR) in 133 pairs of primary HCC samples. A survival analysis was conducted with the Kaplan-Meier method in the HCC samples and TCGA database. RESULTS: Our results showed that uPA was overexpressed in HCC and was significantly associated with HCC tumor size (P=0.015), differentiation grade (P=0.028), and absence of tumor encapsulation (P=0.010). Patients with high uPA expression levels had a poor outcome (P=0.026). TCGA database analysis was also consistent with our experimental results. CONCLUSIONS: In conclusion, our findings revealed that uPA was overexpressed in HCC and was related to HCC malignant features including tumor size, differentiation grade and absence of tumor encapsulation. High uPA expression had a shorter survival time. It is a potential prognostic biomarker of HCC.
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Ulcerative colitis (UC) is a relapsing inflammatory disease with an unknown precise etiology. The purpose of this study is to investigate the protective effects of Gardenia jasminoides Ellis fruit extracts (GFE) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. GFE (50 mg/kg, 100 mg/kg) were administered orally for 7 days after induction. Meanwhile, the chemical components of GFE were performed by UPLC-QTOF-MS/MS. GFE significantly decreased DAI scores and ameliorated macroscopic and histologic damage. It also reduced the levels of MPO, NO, MDA, IL-1ß, TNF-α, and IL-6, while increasing the level of SOD. Moreover, 56 components were identified in GFE using a UPLC-QTOF-MS/MS method, which can be categorized into six structural groups. Our results indicated that GFE has an ameliorative effect on TNBS-induced colitis in rats, which may further verify its anti-inflammatory and antioxidative properties. Therefore, GFE can be a promising protective agent of colitis that deserves further investigation.
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PURPOSE: By using integrative RNA sequencing analysis, we identified a novel tumor suppressor, serpin family A member 11 (SERPINA11), which is a serine proteinase inhibitor that belongs to the serpin superfamily. However, the function of SERPINA11 in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the role and molecular mechanism of SERPINA11 in HCC. METHODS: Gene expression patterns of SERPINA11 were analyzed in tissue samples of HCC patients by qRT-PCR. In vitro and in vivo experiments were performed to characterize the function and molecular mechanism of SERPINA11 in the tumor metastasis capacity. RESULTS: SERPINA11 was downregulated in approximately 50% of HCC and significantly associated with metastasis and poor outcome of patients. Functional study demonstrated that SERPINA11 could inhibit cell growth, cell migration and tumor metastasis. Mechanistic investigations suggested that SERPINA11 accelerated urokinase-type plasminogen activator (uPA) degradation to suppress extracellular signal-regulated kinase (ERK1/2) phosphorylation, and thereby subdued metastatic capabilities of HCC cells. CONCLUSION: SERPINA11 plays an important tumor suppressive role in HCC, with possible use as a biomarker and an intervention point for new therapeutic strategies.