Publications by authors named "Junming Xu"

41 Publications

Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals.

Front Microbiol 2021 19;12:673969. Epub 2021 Aug 19.

Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen, China.

Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including , , , , , and , and 131 low-abundance genera (0.01-5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by , , , or . , , and were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.
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http://dx.doi.org/10.3389/fmicb.2021.673969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417382PMC
August 2021

Dyslipidemia in Chinese Pancreatic Cancer Patients: A Two-Center Retrospective Study.

J Cancer 2021 3;12(17):5338-5344. Epub 2021 Jul 3.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies in the world. High cholesterol intake may have a certain association with an elevated risk of PC, though dyslipidemia in PC patients has rarely been reported. In this study, we compared serum lipids levels between PC and non-PC tumor patients and assessed their prognostic value in PC. 271 patients treated at Wuhan Union Hospital from January 2012 to December 2016 and 204 individuals at Shanghai General Hospital from January 2018 to December 2019 were recruited. Their demographic parameters, laboratory data, pathological information, and clinical outcomes were extracted and analyzed. The mRNA expressions of related lipoprotein, low density lipoprotein receptor (LDLR) and high density lipoprotein binding protein (HDLBP), in PC tissues and paired noncancerous tissues and follow-up information were assessed based on the GEO database (GSE15471 and GSE62165) and TCGA database. A total of 172 non-PC tumor patients and 260 PC patients were finally eligible for our analysis. PC patients exhibited higher levels of serum triglyceride, cholesterol, and low-density lipoprotein (LDL) and a lower serum high-density lipoprotein (HDL) level on admission versus the non-PC tumor group. In PC patients, LDLR mRNA expression was upregulated, and HDLBP mRNA expression was downregulated in cancerous tissues compared to these levels in paired noncancerous tissues. The survival analysis revealed that dyslipidemia had a non-significant association with a poor prognosis, but PC patients with a high LDLR level were at risk of poor survival. Dyslipidemia is detected in PC patients but has a non-significant relation to PC prognosis. However, LDLR may be a potential predictive marker for PC prognosis.
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http://dx.doi.org/10.7150/jca.60340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317532PMC
July 2021

Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma.

Int J Biol Sci 2021 22;17(10):2590-2605. Epub 2021 Jun 22.

Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing 100020, China.

Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.
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http://dx.doi.org/10.7150/ijbs.58886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315026PMC
June 2021

Standing and Lying Ni(OH) Nanosheets on Multilayer Graphene for High-Performance Supercapacitors.

Nanomaterials (Basel) 2021 Jun 24;11(7). Epub 2021 Jun 24.

School of Materials Science & Engineering, Zhejiang University, Hangzhou 310027, China.

For conventional synthesis of Ni(OH)/graphene hybrids, oxygen-containing functional groups should be firstly introduced on graphene to serve as active sites for the anchoring of Ni(OH). In this work, a method for growing Ni(OH) nanosheets on multilayer graphene (MLG) with molecular connection is developed which does not need any pre-activation treatments. Moreover, Ni(OH) nanosheets can be controlled to stand or lie on the surface of MLG. The prepared hybrids were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). The growth processes are suggested according to their morphologies at different growth stages. The enhanced electrochemical performances as supercapacitor electrode materials were confirmed by cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) techniques. Ni(OH) nanosheets standing and lying on MLG show specific capacities of 204.4 mAh g and 131.7 mAh g, respectively, at 1 A g based on the total mass of the hybrids and 81.5% and 92.8% capacity retention at a high current density of 10 A g, respectively. Hybrid supercapacitors with as-prepared hybrids as cathodes and activated carbon as anode were fabricated and tested.
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http://dx.doi.org/10.3390/nano11071662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308107PMC
June 2021

Efficient fractionation of moso bamboo by synergistic hydrothermal-deep eutectic solvents pretreatment.

Bioresour Technol 2021 May 18;328:124873. Epub 2021 Feb 18.

Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, National Engineering Lab. for Biomass Chemical Utilization, Key Lab. of Biomass Energy and Material, Jiangsu Province, China.

As an attractive renewable carbon resource, lignocellulose could be exploited to produce high-value-added products. Notably, comprehensive utilization of lignocelluloses and lignin first exploitation is still a challenge during bio-refinery process. In this study, an environmentally benign extraction method via hydrothermal-deep eutectic solvents pretreatment was proposed to separate hemicelluloses and high purity of lignin simultaneously from moso bamboo with most of cellulose retaining in the residues. Hemicelluloses were firstly removed by hydrothermal pretreatment, following with lignin extraction by DESs which was prepared from choline chloride and lactic acid, betaine and lactic acid, respectively. Notably, 98.2 wt% of hemicelluloses were degraded and mainly converted into pentose. Meanwhile, 80.1 wt% of delignification was achieved under the optimum condition (CC/LA, 140℃, 6 h), following with up to 99.49% of lignin purity. The mass balance evaluation demonstrated that the combined hydrothermal-deep eutectic solvents pretreatment is a potential method for efficient fractionation of lignocellulose.
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http://dx.doi.org/10.1016/j.biortech.2021.124873DOI Listing
May 2021

YEATS4 is associated with poor prognosis and promotes epithelial-to-mesenchymal transition and metastasis by regulating ZEB1 expression in breast cancer.

Am J Cancer Res 2021 1;11(2):416-440. Epub 2021 Feb 1.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200080, China.

YEATS domain-containing protein 4 (YEATS4) is implicated in several oncogenic signaling pathways, and its expression is involved in various types of cancer; regardless, the pathophysiologic effects of YEATS4 on breast cancer remain unclear. This study finds that YEATS4 is increasingly expressed with breast cancer progression, and its expression is related to poor outcome and distant metastasis. YEATS4 overexpression in breast cancer cells strengthens their malignant characteristics and , particularly inducing epithelial-to-mesenchymal transition (EMT) and consequently, metastatic capability in breast cancer cells. By contrast, deleting YEATS4 in breast cancer cells with high-grade malignancy reduced these characteristics. With regard to the molecular mechanism, YEATS4 mediates histone H3K27ac at specific sites of the ZEB1 promoter to regulate its expression at the transcription level. Depleting ZEB1 blocks YEATS4-induced EMT, migration, invasion, and metastasis. YEATS4 expression is also positively correlated with ZEB1 expression in patients with breast cancer. Co-expression of YEATS4 and ZEB1 correlates with the shortest distant metastasis-free period. Taken together, our data reveal the critical role of YEATS4 in the progression and metastasis of breast cancer, as well as support YEATS4 as a potential therapeutic target and prognostic biomarker for breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868763PMC
February 2021

TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway.

Front Oncol 2020 19;10:562823. Epub 2021 Jan 19.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activate aryl hydrocarbon receptor (AhR), which may regulate cancer growth and invasion in some malignancies. However, whether TDO2 participates in the metastasis and invasion of HCC has not been explored before. The underlying mechanism played by TDO2 in this process still requires further investigation. Here, we demonstrated that overexpression of TDO2 correlates with advanced stage or malignant traits in HCC patients. Knockdown or inhibition of TDO2 suppressed the migration and invasion of HCC cells and . Epithelial to mesenchymal transition (EMT) is an essential program happened in the initial phase of cancer metastasis. We found that in HCC cells, TDO2 promoted the EMT process evidenced by altered levels of biomarkers for EMT. Mechanically, TDO2 regulated the Kyn production in HCC cell activated aryl hydrocarbon receptor (AhR). Together, these results indicate that TDO2 promotes the EMT of hepatocellular carcinoma through activating Kyn-AhR pathway, thereby participating in the metastasis and invasion of HCC.
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http://dx.doi.org/10.3389/fonc.2020.562823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851084PMC
January 2021

A population-based study of the three major variants of papillary thyroid carcinoma.

J Int Med Res 2021 Feb;49(2):300060520984618

Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objective: To explore the clinicopathological features and relative prognostic risks of the three major variants of papillary thyroid carcinoma (PTC).

Methods: We retrospectively analyzed the clinicopathological characteristics and prognoses of patients with the three major PTC variants, conventional papillary thyroid carcinoma (CPTC), follicular-variant papillary carcinoma (FVPTC), and tall-cell papillary thyroid carcinoma (TCPTC), based on data from the Surveillance, Epidemiology, and End Results database from 2005 to 2009.

Results: A total of 29,555 patients were enrolled. In terms of their demographic and clinicopathological characteristics, TCPTC had the highest prevalence of older patients, men, patients with locally advanced stage (T stage and N stage), and mortality, while FVPTC had the lowest prevalence in relation to these factors. The three variants differed significantly in terms of 5-year overall survival and 5-year disease-specific survival. Cox regression analysis identified male sex, age ≥45 years, and higher American Joint Committee on Cancer and TNM stage as independent factors predicting a poor prognosis in relation to both overall and disease-specific survival.

Conclusions: CPTC, FVPTC, and TCPTC have different clinicopathological characteristics and prognoses, indicating the need for different treatment strategies for these three variants of PTC.
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http://dx.doi.org/10.1177/0300060520984618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869181PMC
February 2021

SOX12 expression is associated with progression and poor prognosis in human breast cancer.

Am J Transl Res 2020 15;12(12):8162-8174. Epub 2020 Dec 15.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.

The sex-determining region Y-box 12 (SOX12) is implicated in several oncogenic signaling pathways of multiple types of cancer; however, the biological effects of SOX12 on breast cancer has yet to be elucidated. Here, we assessed SOX12 expression using real-time quantitative PCR in 142 pairs of breast cancer and adjacent normal tissues (ANTs) and immunohistochemistry in 524 breast cancer and 147 ANTs. The effects of SOX12 on breast cancer progression, clinicopathological variables, and prognostic value were then investigated. SOX12 expression was markedly elevated in breast cancer tissues relative to that in ANTs at both mRNA and protein levels. Positive SOX12 expression was correlated to tumor size ( = 0.005), estrogen receptor (ER) ( = 0.018) and human epidermal growth factor receptor (HER2) ( = 0.004) status, lymph node metastasis ( < 0.001), and the tumor-node-metastasis (TNM) stage ( < 0.001). Notably, the positive rate of SOX12 expression gradually increased with breast cancer progression. Multivariate analysis indicated that SOX12 was an independent prognostic factor for overall survival (OS, = 0.023) and distant metastasis-free survival (DMFS, = 0.012). Subgroup analysis revealed that luminal and HER2 patients with positive SOX12 expression had a shorter OS period than those with negative SOX12 expression. Moreover, SOX12 expression was associated with a high risk of distant metastasis in invasive carcinoma with the lymph node metastasis subgroup. In summary, SOX12 correlates with progression and poor prognosis in human breast cancer, suggesting that SOX12 is a potential target for breast cancer treatment and warrants further functional research.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791485PMC
December 2020

The American Paddlefish Genome Provides Novel Insights into Chromosomal Evolution and Bone Mineralization in Early Vertebrates.

Mol Biol Evol 2021 04;38(4):1595-1607

Key Laboratory of Freshwater Biodiversity Conservation, Ministry of Agriculture and Rural Affairs of P.R. China, Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China.

Sturgeons and paddlefishes (Acipenseriformes) occupy the basal position of ray-finned fishes, although they have cartilaginous skeletons as in Chondrichthyes. This evolutionary status and their morphological specializations make them a research focus, but their complex genomes (polyploidy and the presence of microchromosomes) bring obstacles and challenges to molecular studies. Here, we generated the first high-quality genome assembly of the American paddlefish (Polyodon spathula) at a chromosome level. Comparative genomic analyses revealed a recent species-specific whole-genome duplication event, and extensive chromosomal changes, including head-to-head fusions of pairs of intact, large ancestral chromosomes within the paddlefish. We also provide an overview of the paddlefish SCPP (secretory calcium-binding phosphoprotein) repertoire that is responsible for tissue mineralization, demonstrating that the earliest flourishing of SCPP members occurred at least before the split between Acipenseriformes and teleosts. In summary, this genome assembly provides a genetic resource for understanding chromosomal evolution in polyploid nonteleost fishes and bone mineralization in early vertebrates.
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http://dx.doi.org/10.1093/molbev/msaa326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042750PMC
April 2021

Lignin Based Activated Carbon Using HPO Activation.

Polymers (Basel) 2020 Nov 28;12(12). Epub 2020 Nov 28.

USDA Forest Service, Forest Products Lab., Madison, WI 53726, USA.

Activated carbon (AC) with a very high surface area of over 2000 m/g was produced from low sulfur acid hydrotropic lignin (AHL) from poplar wood using HPO at a moderate temperature of 450 °C (AHL-AC6). ACs with similar surface areas were also obtained under the same activation condition from commercial hardwood alkali lignin and lignosulfonate. Initial evaluation of AC performance was carried out using nitrogen adsorption-desorption and dye adsorption. AHL-AC6 exhibited the best specific surface area and dye adsorption performance. Furthermore, the adsorption results of congo red (CR) and methylene blue (MB) showed AHL-AC6 had greater adsorption capacity than those reported in literature. The dye adsorption data fit to the Langmuir model well. The fitting parameter suggests the adsorption is nearly strong and near irreversible, especially for MB. The present study for the first time provided a procedure for producing AC from lignin with Brunauer-Emmett-Teller (BET) surface area >2000 m/g using low cost and low environmental impact HPO at moderate temperatures.
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http://dx.doi.org/10.3390/polym12122829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760334PMC
November 2020

Clinical value of CTLA4 combined with clinicopathological factors in evaluating the prognosis of breast cancer.

Gland Surg 2020 Oct;9(5):1328-1337

Department of General Surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

Background: Clinical prediction of breast cancer prognosis relies on both clinical-pathological features and biological markers. Many studies have revealed that tumor cytotoxic T lymphocyte antigen 4 (CTLA4) expression may present prognostic predicting value in cancers. We intended to explore the prognostic value of significant clinicopathological parameters and CTLA4 for predicting survival of patients with breast cancer.

Methods: A total of 229 breast cancer patients who had radical surgery treatment between Sep 2009 and April 2011 were enrolled in this study. Immunohistochemical staining was performed to evaluate CTLA4 grade and Ki-67 index in breast cancer tissue. Univariate and multivariate logistic analysis, Kaplan-Meier survival analysis and ROC curve were used to explore the association between CTLA4 or clinicopathological parameters and disease-free survival (DFS). A nomogram was constructed based on the regression model to predict DFS of patients with breast cancer.

Results: CTLA4 grade (OR 1.730, 95% CI: 1.213-2.468, P=0.002), Ki-67 (OR 1.449, 95% CI: 1.069-1.964, P=0.017) and N stage (lymph node metastasis) (OR 2.268, 95% CI: 1.588-3.303, P=0.000) showed significantly association with DFS of breast cancer patients. All these factors were independent predictors for poor survival, as patients with stage N2-3 tumors, high CTLA4 grade and Ki-67 index showed low survival probability (P<0.01). The conjunction of these factors exhibited good discrimination value (AUC 0.815, 95% CI: 0.749-0.882, P=0.000). Nomogram performed based on CTLA4 grade, Ki-67 index and N stage provided an efficient method to predict DFS of patients with breast cancer.

Conclusions: The high expression of CTLA4 and Ki-67 together with lymph node metastasis in breast cancer are independent risk factors that affect the prognosis of breast cancer patients. They have the potentiality to be utilized conjunctively as predictor in clinical practice.
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http://dx.doi.org/10.21037/gs-20-359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667109PMC
October 2020

OSR1 phosphorylates the Smad2/3 linker region and induces TGF-β1 autocrine to promote EMT and metastasis in breast cancer.

Oncogene 2021 01 13;40(1):68-84. Epub 2020 Oct 13.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China.

Oxidative stress-responsive kinase 1 (OSR1) plays a critical role in multiple carcinogenic signal pathways, and its overexpression has been found in various types of cancer; however, the pathophysiological role of OSR1 in breast cancer has not been evaluated. This study aims to elaborate on the role of OSR1 in breast cancer metastasis and the specific regulatory mechanism. Our results showed that OSR1 mRNA and protein were upregulated in both human breast cancer samples and cell lines. Moreover, phosphorylated OSR1 (p-OSR1) was an independent poor prognostic indicator in patients with breast cancer. OSR1 upregulation induced epithelial-to-mesenchymal transition (EMT) in normal and malignant mammary epithelial cells with the increasing metastatic capacity. In contrast, deleting OSR1 in aggressive breast cancer cells inhibited these phenotypes. OSR1 is the critical activator for transcription factors of EMT. Mechanistically, we found that OSR1 can directly interact and phosphorylate the linker region of Smad2 at Thr220 and Smad3 at Thr179. Phosphorylated Smad2/3 translocated into the nucleus to enhance transforming growth factor-β1 (TGF-β1) autocrine signalling and increase the transcription of EMT regulators. Importantly, interruption of the OSR1-Smad2/3-TGF-β1 signalling axis elicited a robust anti-EMT and anti-metastatic effect in vitro and in vivo. Taken together, we conclude that OSR1-mediated Smad2/3-TGF-β1 signalling promotes EMT and metastasis representing a promising therapeutic target in breast cancer treatment.
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http://dx.doi.org/10.1038/s41388-020-01499-2DOI Listing
January 2021

TDO Promotes Hepatocellular Carcinoma Progression.

Onco Targets Ther 2020 19;13:5845-5855. Epub 2020 Jun 19.

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China.

Purpose: Tryptophan 2,3-dioxygenase (TDO), encoded by the gene TDO2, is an enzyme that catalyses the first and rate-limiting step of tryptophan (Try) degradation in the kynurenine (Kyn) pathway in the liver. Recently, TDO has been demonstrated to be expressed in various human tumours, especially hepatocellular carcinoma (HCC). However, the role of TDO in HCC is still not very clear. Here, we studied the role of TDO in HCC.

Methods: We demonstrated that TDO is overexpressed in human HCC tissues and is significantly correlated with malignant phenotype characteristics, including tumour size, tumour differentiation, vascular invasion, etc. Kaplan-Meier analysis showed a poor overall survival rate in patients with TDO-overexpressing tumours. In addition, the effects of TDO on HCC tumour growth and metastasis were detected both in vivo and in vitro. TDO overexpression facilitated HCC cell growth, invasion and migration.

Conclusion: Our results suggest that TDO positively regulates HCC proliferation and invasion and acts as a new prognostic biomarker of HCC.
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http://dx.doi.org/10.2147/OTT.S252929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311207PMC
June 2020

Circular RNA circZNF566 promotes hepatocellular carcinoma progression by sponging miR-4738-3p and regulating TDO2 expression.

Cell Death Dis 2020 06 12;11(6):452. Epub 2020 Jun 12.

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080, Shanghai, China.

As a recently discovered noncoding RNA, circular RNAs (circRNAs) have been identified to play key roles in cancer biology; however, the detailed functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unclarified. RNA-seq analysis was used to screen the expression profiles of circRNAs in HCC. CircZNF566 expression in HCC tissues and cell lines was detected by qRT-PCR. In vitro CCK-8, colony formation, wound healing, transwell migration, and invasion assays and in vivo tumorigenesis and metastasis assays were conducted to determine the functions of circZNF566. Luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed to confirm the relationship between circZNF566 and miR-4738-3p. Bioinformatics analysis and luciferase reporter assays were employed to determine whether miR-4738-3p regulates tryptophan 2,3-dioxygenase (TDO2) expression. Finally, immunohistochemistry (IHC) was used to detect the level of TDO2 and determine its prognostic value. CircZNF566 was significantly upregulated in HCC tissues and cell lines. High circZNF566 expression in HCC tissues was positively correlated with clinicopathological features and poor prognosis. Functionally, in vitro experiments showed that circZNF566 promoted HCC cell migration, invasion, and proliferation, whereas in vivo experiments showed that circZNF566 promoted tumorigenesis and metastasis. Mechanistically, circZNF566 acted as a miR-4738-3p sponge to relieve the repressive effect of miR-4738-3p on its target TDO2. In addition, miR-4738-3p suppressed HCC cell migration, invasion, and proliferation, while TDO2 was positively correlated with pathological features and poor prognosis and promoted cell migration, invasion, and proliferation in HCC. CircZNF566 is a novel tumor promoter in HCC and functions through the circZNF566/ miR-4738-3p /TDO2 axis; in addition, circZNF566 may serve as a novel diagnostic marker, prognostic indicator, and target for the treatment of HCC.
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http://dx.doi.org/10.1038/s41419-020-2616-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293356PMC
June 2020

High expression of OSR1 as a predictive biomarker for poor prognosis and lymph node metastasis in breast cancer.

Breast Cancer Res Treat 2020 Jul 18;182(1):35-46. Epub 2020 May 18.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China.

Purpose: Oxidative stress-responsive kinase 1 (OSR1) plays a crucial role in regulating diverse cellular pathophysiologic functions, including ion homeostasis, development, differentiation, angiogenesis, invasive migration, and metastasis. Regardless, the clinical significance of OSR1 in breast cancer is scarce. The current study was conducted to evaluate the effect of OSR1 on the prognosis of patients with breast cancer with a long-term follow-up.

Methods: OSR1 expression in formalin-fixed and paraffin-embedded tissue specimens was analyzed. These specimens were collected from 551 evaluable breast cancer cases by immunohistochemistry (IHC). OSR1 expression was dichotomized based on the H-score in IHC. The effects of OSR1 levels on the clinicopathological attributes and survival prediction in patients with breast cancer were explored.

Results: Among 551 specimens, 183 (33.2%) exhibited high expression of OSR1 in tumor cells. High OSR1 levels were markedly correlated with histologic grade (P = 0.035), ER (P < 0.001) and PgR (P = 0.043) expression, lymph node involvement (P < 0.001), TNM stage (P < 0.001), and axillary surgery procedures (P = 0.003). Univariate analysis results indicate that patients with high OSR1 expression had significantly poor overall survival (P < 0.001), distant disease-free survival (P < 0.001), and breast cancer-specific survival (P < 0.001). Multivariable Cox regression analyses suggest that OSR1 expression was an independent predictive marker of poor prognosis and lymph node metastasis (HR 3.224, 95% CI 1.182-8.702, P = 0.023) in patients with breast cancer.

Conclusions: Our findings indicate that OSR1 is a significantly independent prognosis index for patients with breast cancer with respect to distant disease-free survival, overall survival, and breast cancer-specific survival. High OSR1 expression caused an increase in deaths specifically attributed to breast cancer and was related to increased lymph node metastasis. However, the precise cellular mechanisms for OSR1 in breast cancer require further research.
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http://dx.doi.org/10.1007/s10549-020-05671-wDOI Listing
July 2020

Methanolysis Fractionation and Catalytic Conversion of Poplar Wood toward Methyl Levulinate, Phenolics, and Glucose.

J Agric Food Chem 2019 Sep 26;67(35):9840-9850. Epub 2019 Aug 26.

Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry , Key Lab. of Biomass Energy and Material, Jiangsu Province, National Engineering Lab. for Biomass Chemical Utilization, Key and Open Lab. on Forest Chemical Engineering , SFA, Nanjing 210042 , People's Republic of China.

In the present study, methanolysis of poplar biomass was conducted for the selective transformation of hemicellulose and lignin, which leads to methyl glycosides (mainly C5 glycosides) and lignin fragments in the liquefied products that can be separated according to their difference in hydrophilicity. The distribution of methyl glycosides and delignification was dependent on the presence of acid catalysts and reaction temperatures. The obtained lignin fraction was separated into solid lignin fragments and liquid lignin oil according to their molecular weight distribution. Subsequently, directional conversion of methyl C5 glycosides into methyl levulinate was performed with dimethoxymethane/methanol as the cosolvent. A yield of 12-30% of methyl levulinate yield (based on the methyl glycoside) was achieved under these conditions. The remaining cellulose-rich substrate showed enhanced susceptibility to enzymatic hydrolysis, resulting in a yield of glucose of above 70%. Overall, the described strategy shows practical implications for the effective valorization of biomass.
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http://dx.doi.org/10.1021/acs.jafc.9b03806DOI Listing
September 2019

Meta-analysis of diffusion-weighted imaging in the differential diagnosis of renal lesions.

Clin Imaging 2018 Nov - Dec;52:264-272. Epub 2018 Aug 23.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address:

Purpose: To assess the diagnostic value of diffusion-weighted imaging (DWI) in distinguishing between renal malignant and benign lesions.

Materials And Methods: Electronic databases were systematically searched to identify original studies evaluating DWI findings on renal lesions from January 2000 through January 2018. Pooled weighted estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operator characteristic (sROC) curve was constructed to calculate the area under the sROC curve (AUC). Publication bias was assessed by using Deeks' asymmetry test.

Results: A total of 15 studies including 1386 renal lesions were eligible in the meta-analysis. The pooled sensitivity and specificity with a corresponding 95% confidence interval (CI) were 0.83 (95% CI: 0.80-0.86) and 0.74 (95% CI: 0.71-0.78), respectively. The PLR, NLR, and DOR were 3.21 (95% CI: 2.39-4.32), 0.24 (95% CI: 0.18-0.30), and 15.95 (95% CI: 11.19-22.71), respectively. The AUC was 0.87 (95% CI: 0.84-0.90). Significant heterogeneity was observed between the included studies. Reference standard, country, and gradient factor were identified as the most important variable sources. No evidence of notable publication bias was reported.

Conclusions: DWI is an informative MRI modality in discriminating benign and malignant lesions and exhibits moderately high diagnostic accuracy. However, it remains inconclusive and limited in the absence of an optimal b value and ADC cutoff value. High-quality prospective studies regarding DWI have yet to be conducted to explore optimal imaging parameters and diagnostic thresholds.
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http://dx.doi.org/10.1016/j.clinimag.2018.08.010DOI Listing
January 2019

ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy.

Onco Targets Ther 2017 3;10:4859-4867. Epub 2017 Oct 3.

Department of General Surgery.

Purpose: Currently, although several clinical trials available give strong suggestions that extension of endocrine therapy has benefits, the risk level at which patients may benefit from extended endocrine therapy remains uncertain. This study aimed to identify the proportion of patients at a substantial risk of late recurrence after 5-year adjuvant endocrine therapy.

Patients And Methods: We reviewed 1,056 female patients with primary breast cancer who underwent curative resection between January 2006 and December 2011. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors.

Results: A total of 327 eligible patients were eventually enrolled in this study. Among them, 42 (12.8%) patients suffered from distant metastasis and 34 (10.4%) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071-4.421; =0.032) and histologic grade 3 disease (HR=2.098, 95% CI=1.300-3.385; =0.002) were significantly associated with high risk of late recurrence. However, only histologic grade 3 (HR=2.212, 95% CI=1.166-4.194; =0.015) was significantly associated with high risk of distant metastasis.

Conclusion: Late relapse after completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and more than three positive nodes were the risk factors of late recurrence, while grade 3 was the only risk factor of late distant metastasis. These patients might benefit from extended endocrine therapy.
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http://dx.doi.org/10.2147/OTT.S142698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633314PMC
October 2017

Renewable platform chemicals from directional microwave-assisted liquefaction coupling stepwise extraction of waste biomass.

Bioresour Technol 2017 Nov 3;244(Pt 1):496-508. Epub 2017 Aug 3.

Research Institute of Forestry New Technology, Chinese Academy of Forestry, Beijing 100091, China. Electronic address:

Directional microwave-assisted liquefaction and stepwise extraction are introduced for producing platform chemicals: aromatics and monosaccharides. When sulfuric acid was used as a catalyst, a 45% monosaccharides yield and a 29% aromatics yield were obtained from bamboo with 0.3g catalyst per 18g methanol and 2g bamboo at 160°C with 10min. Approximately 78-86wt% of the six biomass materials were converted into liquid products. After the stepwise extraction and precipitation process, the yields of monosaccharide derivatives and three phenolic compound fractions were 39-45% and 28-32%, respectively. Monosaccharides from holocellulose collected with a high purity of methyl glycosides were higher than 90%. Aromatic derivatives with different weight-molecular distributions were separated into three fractions with more than 80% phenolics. As their similar chemical properties within each fraction, platform chemicals have great commercial potential for producing high-quality chemicals and biofuels using mild upgrading conditions.
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http://dx.doi.org/10.1016/j.biortech.2017.07.182DOI Listing
November 2017

Draft genome of the lined seahorse, Hippocampus erectus.

Gigascience 2017 06;6(6):1-6

Shenzhen Key Lab of Marine Genomics, Guangdong Provincial Key Lab of Molecular Breeding in Marine Economic Animals, BGI Academy of Marine Sciences, BGI Fisheries, BGI, Shenzhen, Guangdong 518083, China.

Background: The lined seahorse, Hippocampus erectus , is an Atlantic species and mainly inhabits shallow sea beds or coral reefs. It has become very popular in China for its wide use in traditional Chinese medicine. In order to improve the aquaculture yield of this valuable fish species, we are trying to develop genomic resources for assistant selection in genetic breeding. Here, we provide whole genome sequencing, assembly, and gene annotation of the lined seahorse, which can enrich genome resource and further application for its molecular breeding. A total of 174.6 Gb (Gigabase) raw DNA sequences were generated by the Illumina Hiseq2500 platform. The final assembly of the lined seahorse genome is around 458 Mb, representing 94% of the estimated genome size (489 Mb by k-mer analysis). The contig N50 and scaffold N50 reached 14.57 kb and 1.97 Mb, respectively. Quality of the assembled genome was assessed by BUSCO with prediction of 85% of the known vertebrate genes and evaluated using the de novo assembled RNA-seq transcripts to prove a high mapping ratio (more than 99% transcripts could be mapped to the assembly). Using homology-based, de novo and transcriptome-based prediction methods, we predicted 20 788 protein-coding genes in the generated assembly, which is less than our previously reported gene number (23 458) of the tiger tail seahorse ( H. comes ). We report a draft genome of the lined seahorse. These generated genomic data are going to enrich genome resource of this economically important fish, and also provide insights into the genetic mechanisms of its iconic morphology and male pregnancy behavior.
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http://dx.doi.org/10.1093/gigascience/gix030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459928PMC
June 2017

Analysis of the Global Warming Potential of Biogenic CO Emission in Life Cycle Assessments.

Sci Rep 2017 01 3;7:39857. Epub 2017 Jan 3.

Jilin Province Academy of Forestry Research, Changchun, 130033, China.

Biomass is generally believed to be carbon neutral. However, recent studies have challenged the carbon neutrality hypothesis by introducing metric indicators to assess the global warming potential of biogenic CO (GWP). In this study we calculated the GWP factors using a forest growth model and radiative forcing effects with a time horizon of 100 years and applied the factors to five life cycle assessment (LCA) case studies of bioproducts. The forest carbon change was also accounted for in the LCA studies. GWP factors ranged from 0.13-0.32, indicating that biomass could be an attractive energy resource when compared with fossil fuels. As expected, short rotation and fast-growing biomass plantations produced low GWP. Long-lived wood products also allowed more regrowth of biomass to be accounted as absorption of the CO emission from biomass combustion. The LCA case studies showed that the total life cycle GHG emissions were closely related to GWP and energy conversion efficiency. By considering the GWP factors and the forest carbon change, the production of ethanol and bio-power appeared to have higher GHG emissions than petroleum-derived diesel at the highest GWP.
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http://dx.doi.org/10.1038/srep39857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206676PMC
January 2017

Lentivirus-mediated knockdown of CEP55 suppresses cell proliferation of breast cancer cells.

Biosci Trends 2016 Feb 22;10(1):67-73. Epub 2016 Feb 22.

Department of general surgery, Shanghai first people's Hospital, Shanghai Jiao Tong University School of Medicine.

Centrosomal protein 55 (CEP55), as a microtubule-bundling protein, plays an important role in cell cycle regulation. CEP55 has been recognized recently in several human cancers. In this study, we first observed that the mRNA level of CEP55 is commonly up-regulated in breast cancer compared with their normal counterparts as demonstrated by data derived from Oncomine database. To further evaluate the functional role of CEP55 in breast cancer cells. Expression of CEP55 was efficiently knocked down using lentivirus-mediated RNA interference in human breast cancer cell line ZR-75-30, as evidenced by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Further investigations revealed that CEP55 knockdown significantly inhibited cell proliferation and colony formation. Moreover, flow cytometer analysis indicated knockdown of CEP55 induced cell cycle arrested at G0/G1 phase and cell apoptosis. These findings suggest that CEP55 plays a crucial role in promoting breast cancer cell proliferation and it might be a potential therapeutic target in breast cancer.
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http://dx.doi.org/10.5582/bst.2016.01010DOI Listing
February 2016

Reactions of graphene supported Co3O4 nanocubes with lithium and magnesium studied by in situ transmission electron microscopy.

Nanotechnology 2016 Feb 25;27(8):085402. Epub 2016 Jan 25.

Department of Materials Science and Engineering, NUANCE Center, Northwestern University, Evanston, IL 60208, USA.

Reaction beyond intercalation and the utilization of metal ions beyond lithium-ions are two promising approaches for developing the next generation of high capacity and low cost energy storage materials. Here, we use graphene supported Co3O4 nanocubes and study their reaction with lithium, magnesium and aluminum using in situ transmission electron microscopy. On lithiation, the Co3O4 nanocubes decompose to Co metal nanoparticles (2 to 3 nm) and embed in as-formed Li2O matrix; conversely, the CoO nanoparticles form on the Co site accompanying the decomposition of Li2O in the delithiation process. The lithiation process is dominated by surface diffusion of Li(+), and graphene sheets enhance the Li(+) diffusion. However, upon charge with magnesium, the Mg(2+) diffusion is sluggish, and there is no sign of conversion reaction between Mg and Co3O4 at room temperature. Instead, a thin film consisting of metal Mg nanoparticles is formed on the surface of graphene due to a process similar to metal plating. The Al(3+) diffusion is even more sluggish and no reaction between Al and Co3O4 is observed. These findings provide insights to tackle the reaction mechanism of multivalent ions with electrode materials.
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http://dx.doi.org/10.1088/0957-4484/27/8/085402DOI Listing
February 2016

The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.

Drug Des Devel Ther 2015 1;9:5439-45. Epub 2015 Oct 1.

Department of Cardiothoracic Surgery, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, P<0.00001. The rate of FHIT hypermethylation was not significantly different between stage I/II and stage III/IV, odds ratio was 2.98, P=0.06. In addition, FHIT hypermethylation was not significantly associated with ER and PR status. FHIT hypermethylation was not significantly correlated with premenopausal and postmenopausal patients with invasive ductal carcinoma. In summary, our meta-analysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.
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http://dx.doi.org/10.2147/DDDT.S89861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598219PMC
July 2016

Prognostic values of Notch receptors in breast cancer.

Tumour Biol 2016 Feb 1;37(2):1871-7. Epub 2015 Sep 1.

Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, 100 Haining Road, Shanghai, People's Republic of China, 200080.

Notch receptors are frequently deregulated in several human malignancies including human breast cancer. Activation of Notch has been reported to cause mammary carcinomas in mice. However, the prognostic value of individual Notch receptors in breast cancer (BC) patients remains elusive. In the current study, we investigated the prognostic value of Notch receptors in human BC patients. More specifically, we investigated the prognostic value of four Notch receptors in breast cancer patients through "the Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information are from a total of 3554 breast cancer patients. Our results showed that Notch1 messenger RNA (mRNA) high expression was correlated to worsen overall survival (OS) in PgR-negative BC patients. Notch2, Notch3, and Notch4 mRNA high expressions were found to be correlated to better OS for all breast cancer patients. Notch2 was also found to be correlated to better OS in lymph node-negative breast cancer patients and HER2-positive breast cancer patients. These results will be useful for better understanding of the heterogeneity and complexity in the molecular biology of breast cancer and for developing tools to more accurately predict their prognosis and design their customized treatment strategies.
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http://dx.doi.org/10.1007/s13277-015-3961-6DOI Listing
February 2016

Prognostic role of serum carbohydrate antigen 19-9 levels in patients with resectable hepatocellular carcinoma.

Tumour Biol 2015 Apr 19;36(4):2257-61. Epub 2015 Mar 19.

Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, 200080, Shanghai, China,

Serum levels of carbohydrate antigen 19-9 (CA 19-9) were shown to be associated with poorer prognosis in several cancers, but the prognostic role of CA 19-9 levels in patients with hepatocellular carcinoma was unclear. A retrospective cohort of 97 patients with resectable hepatocellular carcinoma was performed to assess the prognostic role of CA 19-9 levels on overall survival in hepatocellular carcinoma. Both Kaplan-Meier product-limit method and multivariate analysis were performed to determine the prognostic role of CA 19-9 levels. The results indicated that among those 97 patients, 24 (24.7%) had elevated preoperative CA 19-9 levels (≥37 U/mL). Elevated serum CA 19-9 levels did not correlate with patient age, gender, tumor size, tumor stage, diabetes, and hepatitis B virus (HBV) infection. Kaplan-Meier product-limit method showed that patients with elevated CA 19-9 levels had poorer survival than those with normal CA 19-9 levels (log-rank test P < 0.001). Multivariate analysis showed that elevated CA 19-9 level was a significantly independent predictor of poorer overall survival (hazard ratio [HR] = 2.56; 95% confidence interval [95% CI] 1.41-4.64, P = 0.002). In addition, tumor stages and multiple tumors were also independent predictors of poorer overall survival in hepatocellular carcinoma (P < 0.01). In conclusion, serum CA 19-9 levels have an independent prognostic role in patients with resectable hepatocellular carcinoma. Elevated CA 19-9 level is significantly associated with poorer overall survival in hepatocellular carcinoma.
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http://dx.doi.org/10.1007/s13277-014-2435-6DOI Listing
April 2015

Cardiac tamponade following liver transplantation after intrapericardial control of the suprahepatic vena cava.

Liver Transpl 2015 Mar 20;21(3):339-43. Epub 2015 Jan 20.

Department of General Surgery, the First People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China; Dumont-University of California Los Angeles Transplant and Liver Cancer Center, Pfleger Liver Institute, Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.

Transabdominal intrapericardial control of the suprahepatic inferior vena cava (SIVC) is a rather uncommon procedure occasionally required in conjunction with complicated liver transplantation (LT) and hepatobiliary surgery. Experience with this technique is limited. Here we report 6 cases of LT in which transabdominal intrapericardial control of the SIVC was necessary. After institutional review board approval was obtained, a single-center, retrospective review was conducted from January 1991 to December 2013 to identify adult cases (age > 18 years) of LT in which transabdominal intrapericardial isolation of the SIVC was necessary. Among 4102 adult LT cases in the study period, 6 such cases were identified. To gain access to the pericardial space, a 6- to 9-cm vertical incision was made above the SIVC. After reperfusion, the diaphragmatic incision was partially closed and selectively drained. Pericardial tamponade developed in 1 patient, and it necessitated emergent reoperation and widespread drainage. In conclusion, transabdominal intrapericardial isolation of the SIVC is easily achieved without the need for a separate thoracic incision. However, to be effective, the pericardial incision should be only partially closed, and the pericardial sac should be drained liberally. Such patients should be carefully monitored for signs and symptoms of pericardial tamponade, the development of which should prompt an immediate return to the operating room for emergent decompression and widespread drainage.
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http://dx.doi.org/10.1002/lt.24047DOI Listing
March 2015

Atomic resolution study of reversible conversion reaction in metal oxide electrodes for lithium-ion battery.

ACS Nano 2014 Nov 28;8(11):11560-6. Epub 2014 Oct 28.

Department of Materials Science and Engineering, NUANCE Center, Northwestern University , Evanston, Illinois 60208, United States.

Electrode materials based on conversion reactions with lithium ions have shown much higher energy density than those based on intercalation reactions. Here, nanocubes of a typical metal oxide (Co3O4) were grown on few-layer graphene, and their electrochemical lithiation and delithiation were investigated at atomic resolution by in situ transmission electron microscopy to reveal the mechanism of the reversible conversion reaction. During lithiation, a lithium-inserted Co3O4 phase and a phase consisting of nanosized Co-Li-O clusters are identified as the intermediate products prior to the subsequent formation of Li2O crystals. In delithiation, the reduced metal nanoparticles form a network and breakdown into even smaller clusters that act as catalysts to prompt reduction of Li2O, and CoO nanoparticles are identified as the product of the deconversion reaction. Such direct real-space, real-time atomic-scale observations shed light on the phenomena and mechanisms in reaction-based electrochemical energy conversion and provide impetus for further development in electrochemical charge storage devices.
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http://dx.doi.org/10.1021/nn504806hDOI Listing
November 2014

The high-mobility group nucleosome-binding domain 5 is highly expressed in breast cancer and promotes the proliferation and invasion of breast cancer cells.

Tumour Biol 2015 Feb 15;36(2):959-66. Epub 2014 Oct 15.

Department of General Surgery of Shanghai First People's Hospital, Shanghai Jiaotong University, No. 100 Haining Road, 200080, Shanghai, People's Republic of China,

The high-mobility group nucleosome-binding domain 5 (HMGN5) is a member of the high-mobility group proteins family. Previous study found that HMGN5 is required for tumorigenesis in vitro, and aberrations in the expression of HMGN5 were found in human osteosarcoma, prostate cancer, and squamous cell carcinoma. Nevertheless, the role of HMGN5 in breast cancer remains unclear. This study aimed to investigate the expression and clinical significance of HMGN5 in human breast cancer, confirm the oncogenic role of HMGN5, and explore the mechanism by which HMGN5 contributes to invasion and metastasis. HMGN5 expression was detected in breast cancer tissues and corresponding adjacent non-cancerous tissues from 43 patients by immunohistochemistry, and the clinicopathologic characteristics of all patients were also analyzed. Next, knockdown of HMGN5 protein in MDA-MB-231 cells was performed through a small interfering RNA (siRNA) technique, and cell viability, apoptosis, and invasion were detected by cell vitality test, flow cytometry, and transwell assay, respectively. Immunohistostaining showed that HMGN5 were highly expressed in the nucleus in all breast cancer tissues as compared with the adjacent non-cancerous tissues (ANCT;(73.5 ± 11 vs. 31.0 ± 5 %, P < 0.01). HMGN5 expression level was associated with the poorly differentiated tumor cells, lymph node involvement tumor, and T4 staging tumor. Knockdown of HMGN5 inhibited cell growth, suppressed invasion, and increased cell apoptosis in human breast cancer MDA-MB-231 cells. Western blot analysis demonstrated that the expressions of PCNA, connective tissue growth factor (CTGF), and MMP-9 were decreased in human breast MDA-MB-231 cells depleted of HMGN5. In addition, the apoptotic markers (cleaved PARP and cleaved caspase-3) were significantly increased by HMGN5 knockdown, but microtubule-associated protein 1 light chain 3-II/I (LC3-II/I) did not alter. HMGN5 plays an oncogenic role in human breast cancer by inhibiting cell proliferation and invasion, and activating apoptosis, which could be exploited as a target for therapy in human breast cancer.
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http://dx.doi.org/10.1007/s13277-014-2715-1DOI Listing
February 2015
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