387 research outputs found

    Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice

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    The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable and fertile, showed normal brain morphology, and did not activate endoplasmic reticulum stress pathways. However, parameters of oxidative stress were elevated in the livers of these mice. We found that Sep15 mRNA was enriched during lens development. Further phenotypic characterization of Sep15KO mice revealed a prominent nuclear cataract that developed at an early age. These cataracts did not appear to be associated with severe oxidative stress or glucose dysregulation.Wesuggest that the cataracts resulted from an improper folding status of lens proteins caused by Sep15 deficiency

    Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice

    Get PDF
    The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable and fertile, showed normal brain morphology, and did not activate endoplasmic reticulum stress pathways. However, parameters of oxidative stress were elevated in the livers of these mice. We found that Sep15 mRNA was enriched during lens development. Further phenotypic characterization of Sep15KO mice revealed a prominent nuclear cataract that developed at an early age. These cataracts did not appear to be associated with severe oxidative stress or glucose dysregulation.Wesuggest that the cataracts resulted from an improper folding status of lens proteins caused by Sep15 deficiency

    Negative effects of abamectin on soil microbial communities in the short term

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    With the widespread use of abamectin in agriculture, there is increasing urgency to assess the effects of abamectin on soil microorganisms. Here, we treated plant–soil microcosms with abamectin at concentrations of 0.1 and 1.0 mg/kg and quantified the impacts of abamectin on bulk and rhizosphere soil microbial communities by shotgun metagenomics after 7 and 21 days of exposure. Although abamectin was reported to be easily degradable, it altered the composition of the soil microbial communities, disrupted microbial interactions, and decreased community complexity and stability after 7 days of exposure. After treatment with abamectin at a concentration of 1.0 mg/kg, some opportunistic human diseases, and soil-borne pathogens like Ralstonia were enriched in the soil. However, most ecological functions in soil, particularly the metabolic capacities of microorganisms, recovered within 21 days after abamectin treatment. The horizontal and vertical gene transfer under abamectin treatments increased the levels of antibiotic resistance genes dissemination. Overall, our findings demonstrated the negative effects of abamectin on soil ecosystems in the short-term and highlight a possible long-term risk to public and soil ecosystem health associated with antibiotic resistance genes dissemination

    Research on the Influence of Small-Scale Terrain on Precipitation

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    Terrain plays an important role in the formation, development and distribution of local precipitation and is a major factor leading to locally abnormal weather in weather systems. Although small-scale topography has little influence on the spatial distribution of precipitation, it interferes with precipitation fitting. Due to the arbitrary combination of small, medium and large-scale terrain, complex terrain distribution is formed, and small-scale terrain cannot be clearly defined and removed. Based on the idea of bidimensional empirical mode decomposition (BEMD), this paper extracts small-scale terrain data layer by layer to smooth the terrain and constructs a macroterrain model for different scales in Central China. Based on the precipitation distribution model using multiple regression, precipitation models (B0, B1, B2 and B3) of different scales are constructed. The 18-year monthly average precipitation data of each station are compared with the precipitation simulation results under different scales of terrain and TRMM precipitation data, and the influence of different levels of small-scale terrain on the precipitation distribution is analysed. The results show that (1) in Central China, the accuracy of model B2 is much higher than that of TRMM model A and monthly precipitation model B0. The comprehensive evaluation indexes are increased by 3.31% and 1.92%, respectively. (2) The influence of different levels of small-scale terrain on the precipitation distribution is different. The first- and second-order small-scale terrain has interference effects on precipitation fitting, and the third-order small-scale terrain has an enhancement effect on precipitation. However, the effect of small-scale topography on the precipitation distribution is generally reflected as interference

    Heat Shock Protein 90 Family Isoforms as Prognostic Biomarkers and Their Correlations with Immune Infiltration in Breast Cancer

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    Background. The heat shock protein 90 (HSP90s) family is composed of molecular chaperones composed of four isoforms in humans, which has been widely reported as unregulated in various kinds of cancers. Nevertheless, the role of each HSP90s isoform in prognosis and immune infiltration in distinct subtypes of breast cancer (BRAC) remains unclear. Methods. Public online databases including the Oncomine, UALCAN, Kaplan-Meier Plotter, Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GeneMANIA, and Database for Annotation, Visualization, and Integrated Discovery (DAVID) were integrated to perform bioinformatic analyses and to explore the possible associations among HSP90s gene expression, prognosis, and immune infiltration in BRAC. Results. The mRNA expression of all HSP90s members was elevated in distinct clinical stages and subtypes of BRAC, compared with the normal breast tissue (P<0.05). Overexpressed HSP90AA1 was associated with poor prognosis, particularly, both short overall survival (OS) and release-free survival (RFS) in Basal-like BRAC patients; overexpressed HSP90AB1 and HSP90B1 were both associated with poor RFS in Luminal A BRAC patients, while overexpressed TRAP1 was associated with favorable RFS in Luminal A BRAC patients. Moreover, HSP90s gene expression in BRAC showed correlations with the infiltration of CD8+ T cells, neutrophils, macrophages, and dendritic cells (DCs), as well as the activation of tumor-associated macrophages (TAMs), DCs, and CD4+ helper T (Th) cells. The underlying mechanisms of HSP90s modulating tumor-infiltrating immune cells (TIICs) might be related with their functions in antigen processing and presentation, major histocompatibility complex (MHC) binding, and assisting client proteins. Conclusion. This study demonstrated that HSP90s family genes were overexpressed and might be serve as prognostic biomarkers in subtypes of BRAC. It might be a novel breakthrough point of BRAC treatment to regulate immune infiltration in BRAC microenvironment for more effective anticancer immunity through pharmacological intervention of HSP90s

    The recent advances on carrier materials for microencapsulating lipophilic cores

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    Lipophilic ingredients,such as polyunsaturated fatty acids,play an important role in industrialized foods to fortify the nutrients.However,these materials are normally sensitive to oxygen,light or heat to be oxidized,and hard to flow and mix within the bulk food due to the hydrophobic nature.Microencapsulation of lipophilic materials could effectively extend their shelf lives,mask unsatisfied flavors,change their physicochemical properties,and enhance the mixing capacities.This work reviewed the different carrier materials applied in microencapsulating the lipophilic ingredients,and discussed their characteristics and effects on encapsulation efficiencies and release profiles of lipophilic cores

    A LEAN approach for the determination of residual solvents using headspace gas chromatography (HS-GC) with relative response factors

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    External standard method with headspace gas chromatography (HS-GC) technique has been a common method for residual solvents determination. This study demonstrated a new method, 25 solvents can be simultaneously determined based on pre-determined relative respond factor (RRF) with only injection of sample solution. RRF value was finalized by 2 methods and average value was used for result calculation. Validation was carried out successfully covering specificity, linearity, reporting limit, precision, accuracy, stability and robustness. The result showed that the present method is a quick and economic approach for residual solvents testing from process control to product quality check

    Synthesis of metallic Ni-Co/graphene catalysts with enhanced hydrodesulfurization activity via a low-temperature plasma approach

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    Graphene sheets (GS) supported monometal (Ni, Co) or bimetal (Ni-Co) nanoparticle composites have been conveniently prepared with the assistance of dielectric barrier discharge (DBD) plasma at low temperature. Both graphene oxide and the metal ions (Ni2+, Co2+) can be simultaneously reduced during the DBD plasma treatment in H-2 atmosphere, which gives rise to the uniformly distributed metal nanopartides on the surface of GS. The graphene-based catalysts are used in the catalytic hydrodesulfurization (HDS) of carbonyl sulfide (COS). It is revealed that the bimetallic Ni-Co/GS catalyst exhibits outstanding performance for higher COS conversion compared with the monometal catalysts, suggesting the synergetic effect between Ni and Co active species in the HDS reaction. The presented strategy demonstrates a new pathway for the preparation of graphene-based catalysts with high HDS catalytic performance. (C) 2015 Elsevier B.V. All rights reserved

    Exploiting Two-Step Processed Mixed 2D/3D Perovskites for Bright Green Light Emitting Diodes

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    © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Mixed 2D/3D perovskite films with self-assembled quantum wells have significantly improved the performance of perovskite light emitting diodes (PeLEDs). In this work, such films are fabricated through a two-step interdiffusion method that is widely employed in processing of perovskite solar cells, however, remains rarely explored for PeLEDs. The effects of incorporating large-cation ligand, i.e., butylammonium bromide (BABr) into formamidinium lead bromide (FAPbBr 3 ) based perovskites, in terms of film composition, morphology, optoelectronic properties as well as device performance are thoroughly investigated in this method. By modulating BABr:PbBr 2 ratio in the precursor solution, the optimal device shows a maximum external quantum efficiency (EQE) of 7.36% at 147.7 mA cm −2 and a brightness of 37 720 Cd m −2 at 5 V. The performance is remarkably higher than a reference device without BABr that shows a maximum EQE of 2.53% and a brightness of 6190 Cd m −2 at 5 V. The versatility of this method is further extended to another large-cation ligand, 4-fluoro-benzylammonium bromide (F-BZABr), which leads to maximum EQE of 8.55%. This work indicates two-step processed mixed 2D/3D perovskites are promising for bright green PeLEDs.status: publishe

    The impact of dioctyl phthalate exposure on multiple organ systems and gut microbiota in mice

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    Dioctyl phthalate, commonly known as bis(2-ethylhexyl) phthalate (DEHP), is a widely used plasticizer in various industries and has been shown to directly or indirectly impact human health. However, there is a lack of comprehensive studies evaluating the potential health risks associated with DEHP accumulation in different organs across various age groups. This study aimed to assess the effects of low (50 mg/kg·bw) and high (500 mg/kg·bw) doses of DEHP on five different organs in mice at young (4-week-old) and aged (76-week-old) life stages. Our findings revealed that both low and high doses of DEHP exposure led to significant dose-dependent inflammation in the liver, spleen, and kidney. Furthermore, regardless of age, DEHP exposure resulted in elevated activity of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the liver, as well as increased levels of creatinine (Cr) and urea in the kidney. Moreover, analysis of the fecal microbiota using 16S rRNA sequencing demonstrated that DEHP exposure disrupted the homeostasis of the gut microbiota, characterized by an increased abundance of pathogenic bacteria such as Desulfovibrio and Muribaculum, and a decreased abundance of beneficial bacteria like Lactobacillus. This study provides compelling evidence that DEHP at different concentrations can induce damage to multiple organs and disrupt gut microbiota composition. These findings lay the groundwork for further investigations into DEHP toxicity in various human organs, contributing to a better understanding of the potential health risks associated with DEHP exposure
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