Metastatic pattern of ovarian cancer delineated by tracing the evolution of mitochondrial DNA mutations

Xu Zhiyang,Zhou Kaixiang,Wang Zhenni,Liu Yang,Wang Xingguo,Gao Tian,Xie Fanfan,Yuan Qing,Gu Xiwen,Liu Shujuan,Xing Jinliang 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Ovarian cancer (OC) is the most lethal gynecologic tumor and is characterized by a high rate of metastasis. Challenges in accurately delineating the metastatic pattern have greatly restricted the improvement of treatment in OC patients. An increasing number of studies have leveraged mitochondrial DNA (mtDNA) mutations as efficient lineage-tracing markers of tumor clonality. We applied multiregional sampling and high-depth mtDNA sequencing to determine the metastatic patterns in advanced-stage OC patients. Somatic mtDNA mutations were profiled from a total of 195 primary and 200 metastatic tumor tissue samples from 35 OC patients. Our results revealed remarkable sample-level and patient-level heterogeneity. In addition, distinct mtDNA mutational patterns were observed between primary and metastatic OC tissues. Further analysis identified the different mutational spectra between shared and private mutations among primary and metastatic OC tissues. Analysis of the clonality index calculated based on mtDNA mutations supported a monoclonal tumor origin in 14 of 16 patients with bilateral ovarian cancers. Notably, mtDNA-based spatial phylogenetic analysis revealed distinct patterns of OC metastasis, in which a linear metastatic pattern exhibited a low degree of mtDNA mutation heterogeneity and a short evolutionary distance, whereas a parallel metastatic pattern showed the opposite trend. Moreover, a mtDNA-based tumor evolutionary score (MTEs) related to different metastatic patterns was defined. Our data showed that patients with different MTESs responded differently to combined debulking surgery and chemotherapy. Finally, we observed that tumor-derived mtDNA mutations were more likely to be detected in ascitic fluid than in plasma samples. Our study presents an explicit view of the OC metastatic pattern, which sheds light on efficient treatment for OC patients.

Polishing surface integrity of TC17 aeroengine blades

De Liu,Yaoyao Shi,Xiaojun Lin,Chao Xian,Zhiyang Gu 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.2

Aeroengine blades have high requirements for surface integrity. Through the flexible polishing of TC17 engine blades, the surface integrity of polished blades is improved. First, the influence of process parameters on polishing force and polishing temperature is analyzed through experiments. The influence of parameters on surface roughness is analyzed, and the relationship between wear debris shape and surface morphology under different process parameters are analyzed from the microscopic level. Second, the influence of process parameters on the residual stress of the polished surface is analyzed in accordance with the polishing force and polishing temperature. Then, the variation of the residual stress of the blade after milling and polishing is analyzed. In addition, the microstructure of the metamorphic layer after milling and polishing is analyzed. Experimental results show that reasonable polishing parameters can effectively improve the surface integrity of the blade.

Genome-wide analyses of the NAC transcription factor family to reveal the potential candidate genes responding to powdery mildew in balsam pear

Ning Yu,Liu Jing,Song Bo,Xu Hai,Liu Zhiyang,Chen Longzheng 한국식물생명공학회 2023 Plant biotechnology reports Vol.17 No.6

Powdery mildew (PM) is the most serious disease in balsam pear and usually causes severe yield and quality decreases. Although NAC transcription factors involved in the growth, development, and regulation of biotic and abiotic stress responses have been published for many crops, comprehensive data regarding the structure, evolution, and functions of the NAC family in balsam pear are still unavailable. In this study, a comprehensive analysis of the NAC transcription factor family in balsam pear was performed, and 90 NAC genes of balsam pear (McNAC) were identified and divided into 18 subfamilies. Gene structure and protein motif analyses revealed that the functions of McNAC proteins exhibit diversity during evolution and are mainly involved in the response to light, growth, development, and abiotic and biotic stresses. Fifteen McNAC genes (McNAC03, McNAC09, McNAC15, McNAC19, McNAC25, McNAC29, McNAC34, McNAC47, McNAC55, McNAC59, McNAC61, McNAC69, McNAC71, McNAC73, and McNAC78) were differentially expressed after PM pathogen infection. Moreover, the predicted interacting proteins of 7 genes (McNAC09, McNAC15, McNAC25, McNAC29, McNAC34, McNAC73, and McNAC78) were related to the plant hormone signal transduction, betalain biosynthesis, and sphingolipid metabolism pathways by transcriptomic data, implying that the 7 genes participated in PM pathogen infection through these pathways. Metabolome data showed that nine metabolites in the same pathways were changed after PM infection, which suggests that these 7 McNAC genes could regulate these metabolites through the pathways mentioned above to respond to PM infection. The expression levels of McNAC09, McNAC15, McNAC25 and McNAC34 were further confirmed by qPCR to show the reliability of the obtained RNA-seq data. Interestingly, McNAC34 was predicted to be targeted by miRNA164, indicating that McNAC34 might be involved in the response to PM infection by the miRNA-regulated pathway. This study will provide deep insight into NAC gene family evolution and functions, especially in the response to PM pathogen infection in balsam pear.

Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Qi Guo,Zhiyang Shen,Hongxia Yu,Gaofeng Lu,Yong Yu,Xia Liu,Pengyuan Zheng 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-a, IL-1b, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IkBa and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Guo, Qi,Shen, Zhiyang,Yu, Hongxia,Lu, Gaofeng,Yu, Yong,Liu, Xia,Zheng, Pengyuan The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Candidate Pruning-Based Differentially Private Frequent Itemsets Mining

Yangyang Xu,Zhaobin Liu,Zhonglian Hu,Zhiyang Li 보안공학연구지원센터 2016 International Journal of Database Theory and Appli Vol.9 No.7

Frequent Itemsets Mining(FIM) is a typical data mining task and has gained much attention. Due to the consideration of individual privacy, various studies have been focusing on privacy-preserving FIM problems. Differential privacy has emerged as a promising scheme for protecting individual privacy in data mining against adversaries with arbitrary background knowledge. In this paper, we present an approach to exploring frequent itemsets under rigorous differential privacy model, a recently introduced definition which provides rigorous privacy guarantees in the presence of arbitrary external information. The main idea of differentially privacy FIM is perturbing the support of item which can hide changes caused by absence of any single item. The key observation is that pruning the number of unpromising candidate items can effectively reduce noise added in differential privacy mechanism, which can bring about a better tradeoff between utility and privacy of the result. In order to effectively remove the unpromising items from each candidate set, we use a progressive sampling method to get a super set of frequent items, which is usually much smaller than the original item database. Then the sampled set will be used to shrink candidate set. Extensive experiments on real data sets illustrate that our algorithm can greatly reduce the noise scale injected and output frequent itemsets with high accuracy while satisfying differential privacy.

Dynamic Response of High Strength Steel Beams Subjected to Explosion Induced Blast Load

Xinchang Feng,Xiyue Liu,Zhiyang He,Shuxin Bai,Shun Li,Yu Tang 한국강구조학회 2023 International Journal of Steel Structures Vol.23 No.6

A series of anti-explosion tests were performed on H-type high strength steels (Q460JSC and HQ600) and ordinary steels (Q345B) to address the problem of anti-explosion in the technical application of high strength steel. The dynamic behavior of steel beams during explosion and the propagation of shock waves were analyzed. The effects of proportionate distance, steel strength, high-span ratio, section shapes were investigated. The finite element software (ANSYS/LS-DYNA) was used to analyze the anti-explosion performance of high strength steel beams. The finite element models which adopted modified Johnson–Cook constitutive model and damage criterion were validated by comparing with the experimental results. The influence factors of anti-explosion performance of high strength steel were explored by numerical simulation as well. The results reveal that under near-explosion conditions, the peak values of overpressure predicted by empirical formulas are often less than the experimental outcomes. As the scaled distance reduces, the damage to the steel beam increases, making it more prone to local fracture. By decreasing the scaled distance, increasing the high-span ratio, and strengthening the constraint of H-type steel beam, the deformation and damage of steel beams can reduce. The results provide an effective basis to evaluate the safety of high strength steel beams applied in practical engineering when subjected to explosion.

Differential Privacy via Weighted Sampling Set Cover

Zhonglian Hu,Zhaobin Liu,Yangyang Xu,Zhiyang Li 보안공학연구지원센터 2016 International Journal of Security and Its Applicat Vol.10 No.4

Differential privacy is a security guarantee model which widely used in privacy preserving data publishing, but the query result can’t be used in data research directly, especially in high-dimensional datasets. To address this problem, we propose a dimensionality reduction method. The core idea of this method is using a series of low-dimensional datasets to reconstruct a high-dimensional dataset, it improves data availability eventually. The main issue of this method is the reconstruction integrity, so a special sampling via set cover model is proposed in this article, which builds a multidimensional composite marginal tables set as a new middleware in differential privacy model. As a result, any form of disjunctive queries can be answered, and the accuracy of data query is improved. The experiment results also show the effectiveness of our method in practice.