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1.
Ji Hye Yang Sae Kwang Ku IL Je Cho Je Hyeon Lee Chang-Su Na Sung Hwan Ki 《International journal of molecular sciences》2021,22(4)
Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl4)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl4-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway. 相似文献
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3.
Deepika M. Malini Raajan N. R. Srinivasan A. 《Multimedia Tools and Applications》2022,81(9):12701-12724
Multimedia Tools and Applications - The three-dimensional models of brain tumors serve as diagnostic assistance for physicians, surgeons, and radiologists. The proposed system establishes an... 相似文献
4.
Shin Hansub Sim Sungyong Kwon Hyukyoon Hwang Sangheum Lee Younho 《International Journal of Information Security》2022,21(1):25-36
International Journal of Information Security - This paper deals with a well-known problem in the area of the smudge attacks: when a user draws a pattern to unlock the pattern lock on a smartphone... 相似文献
5.
Engineering new glass compositions have experienced a sturdy tendency to move forward from (educated) trial-and-error to data- and simulation-driven strategies. In this work, we developed a computer program that combines data-driven predictive models (in this case, neural networks) with a genetic algorithm to design glass compositions with desired combinations of properties. First, we induced predictive models for the glass transition temperature (Tg) using a dataset of 45,302 compositions with 39 different chemical elements, and for the refractive index (nd) using a dataset of 41,225 compositions with 38 different chemical elements. Then, we searched for relevant glass compositions using a genetic algorithm informed by a design trend of glasses having high nd (1.7 or more) and low Tg (500 °C or less). Two candidate compositions suggested by the combined algorithms were selected and produced in the laboratory. These compositions are significantly different from those in the datasets used to induce the predictive models, showing that the used method is indeed capable of exploration. Both glasses met the constraints of the work, which supports the proposed framework. Therefore, this new tool can be immediately used for accelerating the design of new glasses. These results are a stepping stone in the pathway of machine learning-guided design of novel glasses. 相似文献
6.
Ping-Chi Hsu Jia-Ying Jhong Li-Ping Huang Kuo-Hsin Lee Hsin-Pao Chen Yue-Leon Guo 《International journal of molecular sciences》2021,22(8)
Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system. 相似文献
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8.
Shannon Lee Scott L. Carnahan Georgiy Akopov Philip Yox Lin-Lin Wang Aaron J. Rossini Kui Wu Kirill Kovnir 《Advanced functional materials》2021,31(16):2010293
Noncentrosymmetric (NCS) tetrel pnictides have recently generated interest as nonlinear optical (NLO) materials due to their second harmonic generation (SHG) activity and large laser damage threshold (LDT). Herein nonmetal-rich silicon phosphides RuSi4P4 and IrSi3P3 are synthesized and characterized. Their crystal structures are reinvestigated using single crystal X-ray diffraction and 29Si and 31P magic angle spinning NMR. In agreement with previous report RuSi4P4 crystallizes in NCS space group P1, while IrSi3P3 is found to crystallize in NCS space group Cm, in contrast with the previously reported space group C2. A combination of DFT calculations and diffuse reflectance measurements reveals RuSi4P4 and IrSi3P3 to be wide bandgap (Eg) semiconductors, Eg = 1.9 and 1.8 eV, respectively. RuSi4P4 and IrSi3P3 outperform the current state-of-the-art infrared SHG material, AgGaS2, both in SHG activity and laser inducer damage threshold. Due to the combination of high thermal stabilities (up to 1373 K), wide bandgaps (≈2 eV), NCS crystal structures, strong SHG responses, and large LDT values, RuSi4P4 and IrSi3P3 are promising candidates for longer wavelength NLO materials. 相似文献
9.
Cell surface proteoglycans are known to be important regulators of many aspects of cell behavior. The principal family of transmembrane proteoglycans is the syndecans, of which there are four in mammals. Syndecan-1 is mostly restricted to epithelia, and bears heparan sulfate chains that are capable of interacting with a large array of polypeptides, including extracellular matrix components and potent mediators of proliferation, adhesion and migration. For this reason, it has been studied extensively with respect to carcinomas and tumor progression. Frequently, but not always, syndecan-1 levels decrease as tumor grade, stage and invasiveness and dedifferentiation increase. This parallels experiments that show depletion of syndecan-1 can be accompanied by loss of cadherin-mediated adhesion. However, in some tumors, levels of syndecan-1 increase, but the characterization of its distribution is relevant. There can be loss of membrane staining, but acquisition of cytoplasmic and/or nuclear staining that is abnormal. Moreover, the appearance of syndecan-1 in the tumor stroma, either associated with its cellular component or the collagenous matrix, is nearly always a sign of poor prognosis. Given its relevance to myeloma progression, syndecan-1-directed antibody—toxin conjugates are being tested in clinical and preclinical trials, and may have future relevance to some carcinomas. 相似文献
10.
Nienke Visser Harm Jan Lourens Gerwin Huls Edwin Bremer Valerie R. Wiersma 《International journal of molecular sciences》2021,22(5)
Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease. 相似文献