ABSTRACT
Aims
This research aimed to investigate the specific mechanism of methyltransferase like 3 (METTL3) in the progression of diabetic kidney disease (DKD).
Materials and Methods
The model of ...diabetic kidney disease was established with HK‐2 cells and mice in vitro and in vivo. The N6 methyladenosine (m6A) contents in the cells and tissues were detected with a commercial kit and the m6A levels of PTEN induced putative kinase 1 (PINK2) were detected with a MeRIP kit. The mRNA and protein levels were determined with RT‐qPCR and western blot. The ROS, TNF‐α, and IL‐6 levels were assessed with ELISA. The cell proliferative ability was measured by a CCK‐8 assay and cell apoptosis was determined with TUNEL staining. The HE and Masson staining was performed to observe the renal morphology. The RIP assay was conducted to detect the interaction between METTL3/YTHDF2 and PINK1.
Results
The m6A content and METTL3 levels were prominently elevated in diabetic kidney disease. METTL3 silencing promoted the cell growth and the expression of LC3 II, PINK1, and Parkin, while inhibiting the cell apoptosis and the expression of LC3 I and p62 in the high glucose (HG) stimulated HK‐2 cells. METTL3 silencing also decreased the ROS, TNF‐α, and IL‐6 levels in diabetic kidney disease. PINK1 silencing neutralized the function of sh‐METTL3 in the HG stimulated HK‐2 cells. The HE and Masson staining showed that METTL3 silencing alleviated the kidney injury induced by DKD. METTL3 silencing decreased the m6A levels of PINK1, while increased the mRNA levels of PINK1 which depended on YTHDF2.
Conclusions
METTL3 silencing could inhibit the progression of diabetic nephropathy in vivo and in vitro by regulating the m6A modification of PINK1, which depends on YTHDF2. Our research lays the theoretical foundation for the precise treatment of diabetic kidney disease and the development of targeted drugs in the future.
METTL3 mediates the progression of diabetic nephropathy through regulating the apoptosis and mitophagy of renal tubular epithelial cells. Mechanistically, METTL3 regulates the m6A modification and expression of PINK1 dependent on YTHDF2. We hope these findings could provide novel targets for the treatment of diabetic nephropathy disease.
Complex multi-vessel encounter situations are a challenging problem for ships to avoid collisions, and the International Regulations for Preventing Collision at Sea, 1972 (COLREGs) do not provide a ...clear delineation of multi-vessel encounter situations and the responsibility of collision avoidance (CA). Furthermore, Marine Autonomous Surface Ships (MASS), which realize autonomous navigation functions, face the problem of recognizing complex multi-ship encounter situations and the corresponding CA decisions. In this study, we adopt the velocity obstacle (VO) algorithm to visualize and identify the danger of multi-ship encounters with the own ship (OS) as the first viewpoint. Additionally, we consider the motion changes in target ships (TSs) and their possible CA behaviors as the basis of the ship’s CA decision-making. According to COLREGs, a simplified method for classifying the encounter situations of multiple clustered ships is proposed, considering the coupling of collision hazards and CA responsibilities between related TSs. On this basis, the corresponding CA decisions for each classified situation are proposed, and a large number of simulation experiments are conducted based on the proposed method by considering the three-ship and four-ship encounter model in the Imazu problem as an example. The experimental results indicate that the proposed method can effectively recognize the complex multi-ship encounter situation in the Imazu problem, and it can adjust the CA measures of the OS in time according to the COLREGs and the behavior of TSs. This provides the basis and reference for MASS when facing complex multi-ship encounter situations.
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•Transparent polyimides containing different methyl side groups were synthesized.•The effects of methyl were discussed with assistant of density functional theory.•Polyimide exhibits ...the best optical transmittance of 82% at 400 nm, Tg of 407 °C.•Polyimides show excellent solubility in common solvents.
Highly transparent polyimides (PIs) with excellent combined properties are in great demand for flexible optical devices. In this work, transparent PIs were synthesized by fluorinated aromatic dianhydride (6FDA) and three aromatic diamines containing methyl side groups with different amount and position. These PIs possessed moderate to great optical transparency and excellent solubility. With four methyl groups at 2,2′,5,5′-position in diamine, 2255TMB–PI exhibited the best transmittance up to 82% at 400 nm. In all cases, PIs were determined to have low dielectric constants (2.84–2.99) and high glass transition temperature (above 390 °C, even up to 407 °C for 2255TMB–PI). In addition, the toughness of these PI films was also proven by a tensile strength of 130–156 MPa. In spite of the electron donating character of methyl groups, their steric hindrance was found to have significant effect on the combination properties of PIs. Spatial structures and packing morphology are thought to be the main contribution. Therefore, this work provided an easy way to prepare highly transparent polyimides with excellent combined properties by controlling steric hindrance through methyl side groups.
•A prediction model of lighting and shading coupling control behavior is proposed.•The preferences and control habits of occupants were investigated and classified.•The indoor work plane illumination ...was predicted by a machine learning model.•The preference diversity of occupants greatly affect the prediction accuracy.
Lighting control in office buildings is driven by occupant's demand for indoor light environment. The control behavior not only has a direct impact on occupants’ visual comfort, but also relates with the building lighting energy consumption. However, due to the effect of glare, lighting control is often associated with shading adjustment. In this regard, this paper proposed a prediction model which can accurately describe the lighting and shading coupling control behavior by fully considering the difference and diversity of occupants. The light environment preferences and the usage habits of lighting and shading system of occupants were firstly investigated and classified by means of questionnaire. Markov model and log-logistic survival model were introduced to quantitatively describe the probability distribution of various shading and lighting control behaviors. On this basis, combined with the indoor workplane illumination prediction model, the behavior of occupant's lighting and shading coupling control can be predicted. By comparing the four models considering or not considering the diversity and coupling effect, it is found that the proposed coupling prediction model shows better performance, the maxium error rate is only 13.04% for the lighting energy consumption prediction.
OBJECTIVE:To research the anti-cancer mechanism of the Traditional Chinese Medicine Fanbaicao(Herba Potentillae Discoloris) oil in the human hepatoma cell line Hep G2.METHODS:Gas chromatography was ...used to analyze the components of Fanbaicao(Herba Potentillae Discoloris).We tested the inhibitory effect of Fanbaicao(Herba Potentillae Discoloris) oil on the human hepatoma cell line Hep G2 in vitro using 3-(4,5-Dimet hylt hiazol-2-yl)-2,5-dip henyltetrazoliumbromide assays.Fluorescence activating cell sorter analysis was used to examine the levels of apoptosis,and western blot and immunofluorescence were used to detect the expression of p21,p-p21 and CDK4 proteins.RESULTS:Fanbaicao(Herba Potentillae Discoloris)oil contains 45 ingredients,and L-ascorbic acid 2,6-bispalmitate was the main component and accounted for 44.96% of total drive-off peak area.Other components included(Z)-14-met hyl-8-exadecenal-acetal(8.56%),phytol(7.74%) and lauric acid(6.31%).Fanbaicao(Herba Potentillae Discoloris)oil treatment reduced the proliferation of Hep G2 cells and the half growth inhibition concentration(IC50) was 2.03 mg/m L.Furthermore,we also observed significantly increased Hep G2 cell apoptosis in a dose-dependent manner(P < 0.05).Fanbaicao(Herba Potentillae Discoloris) oil significantly increased the expression of p21 and p-p21 and significantly decreased the expression of CDK4 in Hep G2 cells compared with controls(P < 0.01).CONCLUSION:Our results showed that Fanbaicao(Herba Potentillae Discoloris) oil has anti-cancer activities in Hep G2 cells,which is probably related to the upregulation of p21 and p-p21 and downregulation of CDK4 expression.
Outer dense fibers are specific subcellular components of mammal sperm flagella, apart from the axoneme and its associated proteins. As one of the outer dense fibers components, ODF3 is essential for ...the formation of mammal sperm flagella. In the present study, we isolated the Odf3 gene, 1033 bp in length, from Zhikong scallop Chlamys farreri, which was named as Cf-Odf3. It was predicted that Cf-Odf3 encodes a protein of 240 amino acids which contains 5 discontinuous Pro-Gly-Pro repeats. The Cf-Odf3 transcripts were detected in both testis and ovary of C. farreri at various stages through qRT-PCR. The Cf-ODF3 protein synthesized by prokaryotes was purified using Ni2+-NTA affinity chromatography and used to produce its polyclonal antibody. The antibody product was effective and specific as was examined by Western blotting. The Cf-Odf3 transcript and Cf-ODF3 protein were located in intragonadal somatic cells (ISCs), spermatogonia and spermatocytes of C. farreri testes, while no transcription of Cf-Odf3 and synthesis of Cf-ODF3 were detected in spermatids and spermatozoa. The location of Odf3 expression is different from that of vertebrates where ODF3 is synthesized specifically in spermatids and sperm flagella. Moreover, the Cf-Odf3 expression was also detected in ISCs, oogonia and oocytes of the scallop ovaries. Our finding revealed a different characteristic of Odf3 expression between scallop and vertebrates, which implied that Cf-Odf3 played a role in the gametogenesis of C. farreri.
The development of thermostable polyimides (PIs) is urgently required for application in traditional aerospace and newly designing flexible-display substrates. The root to obtain intrinsic ...heat-resistant PIs is to seek novel monomers. Based on the high bond energy of quinoxaline, several quinoxaline diamines, including 3/2-(4-aminophenyl)-2/3-quinoxalin-6-amine (QHDA), 3/2-(4-aminophenyl)-2/3-phenyl quinoxalin-6-amine (QBDA), and 3/2-(4-aminophenyl)-2/3-methylquinoxalin-6-amine (QMDA) were synthesized, and the corresponding PI films were prepared with four aromatic dianhydrides. The introduction of a quinoxaline moiety provided the PI films with excellent thermal properties and an advanced mechanical performance. The QHDA-PIs possessed a high thermal stability with a 5% mass-loss temperature (Td5%) of 528–560 °C, a glass-transition temperature (Tg) of 413–444 °C and a low coefficient of thermal expansion (CTE) of 1 ppm/K for QHDA-m because of its better linearity and closer packing. This study established design rules to tune the properties of quinoxaline PIs by side-group modification.
Novel PI films with quinoxaline moiety exhibited advanced thermal properties and mechanical performance, which are promising potential for flexible display devices. Display omitted
•Three phenylquinoxaline diamines containing different side groups were synthesized.•The polyimide containing quinoxaline showed excellent comprehensive properties.•The properties of polyimide can be adjusted by the side groups of phenylquinoxaline.•The red polyimide film can be obtained using phenylquinoxaline monomer with methyl.
Anaplastic thyroid cancer (ATC) is a rare but lethal human malignant cancer with no known cure. Ellagic acid (EA), a natural plant extract, has shown antitumor activity against multiple cancers; ...however, its effects on the malignant phenotypes of ATC cells remain unknown. This study aimed to evaluate the effects of EA on proliferation, migration, and invasion of ATC cells and further explore the associated signaling mechanisms. The normal human thyroid cell line Nthy-ori3-1 and ATC cell line BHT-101 were used. Cytotoxicity assay was performed using the Cell Counting kit-8 (CCK-8) assay. Cell proliferation, migration, and invasion assays were performed using the CCK-8 and colony formation, wound healing, and Transwell invasion assays, respectively. Western blotting was used to detect the levels of related proteins. β-catenin nuclear protein levels were measured to evaluate the Wnt/β-catenin pathway. The phosphorylation level of the Akt protein was measured and calculated to evaluate the PI3K/Akt pathway. LiCl and IGF-1 were used as pathway agonists to determine the involvement of the corresponding pathway. The results showed that EA inhibited the proliferation, migration, and invasion of ATC cells. Furthermore, both the Wnt/β-catenin and PI3K/Akt pathways were suppressed by EA treatment, and activation of these two pathways reversed the EA-induced inhibition of the pathological phenotypes of ATC cells. These findings demonstrate that EA inhibits proliferation, migration, and invasion of ATC cells by suppressing the Wnt/β-catenin and PI3K/Akt pathways, suggesting that EA is a potential drug candidate for treating ATC and provides a theoretical basis for further in vivo experiments and clinical applications.
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