Publications by authors named "Wenli Guo"

45 Publications

Long non-coding RNA LINC01137 contributes to oral squamous cell carcinoma development and is negatively regulated by miR-22-3p.

Cell Oncol (Dordr) 2021 Jun 2;44(3):595-609. Epub 2021 Apr 2.

Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Purpose: Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. LINC01137 is a recently identified lncRNA of which the functional role in the development of oral squamous cell carcinoma (OSCC) has not been determined yet.

Methods: We analyzed the expression of LINC01137 using a microarray-based OSCC gene expression dataset (GSE31056), and validated the results obtained using RT-qPCR in 26 pairs of primary OSCC tumor tissues and adjacent non-tumor tissues. The proliferative and invasive effects of LINC01137 on OSCC cells were determined using CCK-8, colony formation and transwell assays, respectively. Targeted binding between miR-22-3p and LINC01137 was verified using a dual luciferase reporter assay.

Results: We found that LINC01137 was significantly upregulated in primary OSCCs. LINC01137 knockdown inhibited OSCC cell proliferation, migration and invasion, whereas LINC01137 overexpression induced opposite effects. LINC01137 upregulation along with p53 inhibition enhanced the malignant transformation of oral cells. In addition, we found that miR-22-3p can directly target LINC01137 through interaction with a putative miR-22-3p-binding site present within the LINC01137 sequence. A significant negative correlation was observed between LINC01137 and miR-22-3p expression in primary OSCC specimens. Exogenous overexpression of miR-22-3p markedly reduced the endogenous expression level of LINC01137 in OSCC cells. Additional functional assays showed that miR-22-3p overexpression enhanced the inhibitory effect of siRNA-mediated LINC01137 silencing on OSCC cell proliferation, migration and invasion, whereas miR-22-3p inhibition had the opposite effect.

Conclusions: Our results indicate that LINC01137 functions as an oncogenic lncRNA in OSCC. miR-22-3p can directly target LINC01137 and negatively regulate its expression and function.
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http://dx.doi.org/10.1007/s13402-021-00586-0DOI Listing
June 2021

Metabolomic profiling identifies a novel mechanism for heat stroke‑related acute kidney injury.

Mol Med Rep 2021 04 28;23(4). Epub 2021 Jan 28.

Department of Nephrology, Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.

Heat stroke can induce a systemic inflammatory response, which may lead to multi‑organ dysfunction including acute kidney injury (AKI) and electrolyte disturbances. To investigate the pathogenesis of heat stroke (HS)‑related AKI, a mouse model of HS was induced by increasing the animal's core temperature to 41˚C. Blood samples obtained from the tail vein were used to measure plasma glucose and creatinine levels. Micro‑positron emission tomography‑computed tomography (micro‑PET/CT), H&E staining and transmission electron microscopy were conducted to examine metabolic and morphological changes in the mouse kidneys. Immunohistochemistry (IHC) and western blot analyses were performed to investigate the expression of apoptosis‑inducing factor mitochondria‑associated 2 (Aifm2), high‑mobility group box 1 (HMGB1) and receptor for advanced glycosylation end products (RAGE). Liquid chromatography‑mass spectrometry analysis was conducted to find differential metabolites and signaling pathways. The HS mouse model was built successfully, with significantly increased creatinine levels detected in the serum of HS mice compared with controls, whereas micro‑PET/CT revealed active metabolism in the whole body of HS mice. H&E and TUNEL staining revealed that the kidneys of HS mice exhibited signs of hemorrhage and apoptosis. IHC and western blotting demonstrated significant upregulation of Aifm2, HMGB1 and RAGE in response to HS. Finally, 136 differential metabolites were screened out, and enrichment of the 'biosynthesis of unsaturated fatty acids' pathway was detected. HS‑associated AKI is the renal manifestation of systemic inflammatory response syndrome, and may be triggered by the HMGB1/RAGE pathway. Metabolomics indicated increased adrenic acid, docosahexaenoic acid and eicosapentaenoic acid may serve as metabolic biomarkers for AKI in HS. The findings suggested that a correlation between the HMGB1/RAGE pathway and biosynthesis of unsaturated fatty acids may contribute to the progression of HS‑related AKI.
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http://dx.doi.org/10.3892/mmr.2021.11880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893796PMC
April 2021

Photoluminescence Blinking and Biexciton Auger Recombination in Single Colloidal Quantum Dots with Sharp and Smooth Core/Shell Interfaces.

J Phys Chem Lett 2021 Jan 24;12(1):405-412. Epub 2020 Dec 24.

State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Laser Spectroscopy, Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, China.

There is an inconsistence on whether a smooth core/shell interface can reduce Auger recombination and suppress photoluminescence (PL) blinking in single colloidal quantum dots (QDs). Here, we investigate the influence of a core/shell interface on PL blinking and biexciton Auger recombination by comparing the single-dot PL spectra of CdZnSeS/ZnS core/shell QDs with sharp and smooth interfaces. The inconsistence can be clarified when considering different PL blinking mechanisms. For the single QDs showing Auger blinking, a smooth core/shell interface potential can suppress PL blinking through reducing the Auger recombination. In contrast, we find slightly reduced biexciton Auger recombination rates but increased PL blinking activities in the band-edge carrier (BC)-blinking QDs with the smooth core/shell interface. This is because the smooth interface potential cannot reduce the PL blinking caused by the transfer of electrons to the surface states; however, there is potential to increase electron wave function delocalization for reducing the biexciton Auger recombination rate.
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http://dx.doi.org/10.1021/acs.jpclett.0c03065DOI Listing
January 2021

Biexciton Dynamics in Single Colloidal CdSe Quantum Dots.

J Phys Chem Lett 2020 Dec 3;11(24):10425-10432. Epub 2020 Dec 3.

State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Laser Spectroscopy, Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, China.

The investigation of biexciton dynamics in single colloidal quantum dots (QDs) is critical to biexciton-based applications. Generally, a biexciton exhibits an extremely low photoluminescence (PL) quantum yield as well as very fast PL decay due to strong nonradiative Auger recombination, making it difficult to investigate the biexciton dynamics. Here, we develop a quantitative method based on intensity- and time-resolved photon statistics to investigate the biexciton dynamics in single colloidal QDs. This robust method can be used under high-excitation conditions to determine the absolute radiative and Auger recombination rates of both neutral and charged biexciton states in a single QD level, and the corresponding ratios between the two states agree with the theoretical predictions of the asymmetric band structures of CdSe-based QDs. Furthermore, the surface traps are found to provide additional nonradiative recombination pathways for the biexcitons, and their contributions are quantified by the method.
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http://dx.doi.org/10.1021/acs.jpclett.0c02832DOI Listing
December 2020

Blinking Mechanisms and Intrinsic Quantum-Confined Stark Effect in Single Methylammonium Lead Bromide Perovskite Quantum Dots.

Small 2020 Dec 25;16(51):e2005435. Epub 2020 Nov 25.

State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Laser Spectroscopy, Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, 030006, China.

Lead halide perovskite quantum dots (QDs) are promising materials for next-generation photoelectric devices because of their low preparation costs and excellent optoelectronic properties. In this study, the blinking mechanisms and the intrinsic quantum-confined Stark effect (IQCSE) in single organic-inorganic hybrid CH NH PbBr perovskite QDs using single-dot photoluminescence (PL) spectroscopy is investigated. The PL quantum yield-recombination rates distribution map allows the identification of different PL blinking mechanisms and their respective contributions to the PL emission behavior. A strong correlation between the excitation power and the blinking mechanisms is reported. Most single QDs exhibit band-edge carrier blinking under a low excitation photon fluence. While under a high excitation photon fluence, different proportions of Auger-blinking emerge in their PL intensity trajectories. In particular, significant IQCSEs in the QDs that exhibit more pronounced Auger-blinking are observed. Based on these findings, an Auger-induced IQCSE model to explain the observed IQCSE phenomena is observed.
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http://dx.doi.org/10.1002/smll.202005435DOI Listing
December 2020

Effects of nursing methods for emergency pci and non-emergency PCI on the treatment of patients with acute myocardial infarction.

J Pak Med Assoc 2020 Sep;70 [Special Issue](9):31-37

Department of Anus & Intestine, Hiser Hospital, Shibei District, Qingdao, Shandong, China.

Objective: To study the effect of emergency nursing methods on the treatment of acute myocardial infarction (AMI).

Methods: A total of 100 patients with AMI were divided into emergency percutaneous coronary intervention (PCI) group (group A, 50 cases) and non-emergency PCI control group (group B, 50 cases). The clinical outcome, average left ventricular ejection fraction (LVEF), angina pectoris, heart failure, and reperfusion arrhythmia after myocardial infarction were compared between the two groups.

Results: The average hospitalization days of emergency PCI group were less than those of the control group, and the incidence of angina pectoris and heart failure after myocardial infarction was lower than that of the control group. The average LVEF of emergency PCI group was higher than that of the control group.

Conclusions: This shows that emergency nursing of AMI can quickly and efficiently dredge the infarcted artery, reduce the occurrence of cardiovascular events after AMI and the average hospitalization days of patients, improve the left ventricular function and prevent heart failure. This method is a very effective treatment for improving the prognosis in patients with AMI.
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September 2020

Expression, association with clinicopathological features and prognostic potential of CEP55, p-Akt, FoxM1 and MMP-2 in astrocytoma.

Oncol Lett 2020 Aug 17;20(2):1685-1694. Epub 2020 Jun 17.

Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

Centrosomal protein 55 (CEP55) is a member of the centrosomal-associated protein family and participates in the regulation of cytokinesis during cell mitosis. However, aberrant CEP55 protein expression has been observed in human tumors. In addition, CEP55 regulates the biological functions of tumors by inducing the Akt pathway and upregulating forkhead box protein M1 (FoxM1) and matrix metalloproteinase-2 (MMP-2). In the present study, the levels, clinicopathological features and prognostic potential of CEP55, phosphorylated Akt (p-Akt), FoxM1 and MMP-2 in astrocytoma were evaluated. CEP55, p-Akt, FoxM1 and MMP-2 levels were examined in 27 normal brain tissues and 262 astrocytoma tissues by using immunohistochemistry. Furthermore, Kaplan-Meier analysis and Cox proportional hazards models were applied to predict the prognosis of patients with astrocytoma. The results indicated that expression levels of CEP55 and other proteins were elevated in human astrocytoma compared with those in normal brain tissue. The levels of the selected proteins were increased as the tumor grade increased. Furthermore, CEP55 expression was positively correlated with p-Akt, FoxM1 and MMP-2 levels in astrocytoma. Overall survival analysis revealed that patient prognosis was associated with CEP55, p-Akt, FoxM1 and MMP-2 levels, as well as with the tumor grade and patient age. Furthermore, CEP55, FoxM1, tumor grade and patient age were independent prognostic factors in astrocytoma according to multivariate analysis. Taken together, the present results suggested that CEP55, p-Akt, FoxM1 and MMP-2 have crucial roles in the progression and prognosis of human astrocytoma and that CEP55 and FoxM1 may be potential therapeutic targets.
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http://dx.doi.org/10.3892/ol.2020.11742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377175PMC
August 2020

TNF-α-dependent lung inflammation upregulates superoxide dismutase-2 to promote tumor cell proliferation in lung adenocarcinoma.

Mol Carcinog 2020 09 16;59(9):1088-1099. Epub 2020 Jul 16.

Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China.

Manganese superoxide dismutase (SOD-2), an important primary antioxidant enzyme located in mitochondria, plays a critical role in tumor progression. Reportedly, the proinflammatory cytokine, tumor necrosis factor (TNF)-α, can increase SOD-2 expression in a human lung adenocarcinoma cell line in vitro, indicating that TNF-α-mediated inflammation may regulate SOD-2 expression, which may be related to cancer promotion. Using a urethane-induced inflammation-driven lung adenocarcinoma (IDLA) mice model, we investigated whether and how TNF-α-mediated inflammation upregulated SOD-2 expression in lung adenocarcinoma. Our results showed that SOD-2 was mostly expressed on surfactant protein-C AT-II cells (alveolar type II cell) and tumor cells in IDLA mice, which were surrounded by CD68 macrophages. Blocking TNF-α-dependent inflammation downregulated SOD-2 expression in inflamed lung tissues at the protumor stage and also inhibited SOD-2 expression in tumor cells in the IDLA model. In human lung adenocarcinoma, both the number of infiltrating CD68 macrophages and TNF-α expression correlated positively with SOD-2 expression, which is related to lymph node metastasis and TNM stage. We collected the conditioned medium from lipopolysaccharide-activated phorbol myristate acetate-induced THP1 (M1) cells to stimulate A549 and H1299 cells and observed that THP1-M1 upregulated SOD-2 by secreting TNF-α. Blocking SOD-2 expression significantly inhibited TNF-α-induced cell proliferation in A549 and H1299 cells in vitro. Thus, TNF-α-mediated lung inflammation can upregulate SOD-2 expression in lung adenocarcinoma, and macrophages contribute to SOD-2 upregulation by secreting TNF-α.
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http://dx.doi.org/10.1002/mc.23239DOI Listing
September 2020

High mobility group box-1 protects against Aflatoxin G-induced pulmonary epithelial cell damage in the lung inflammatory environment.

Toxicol Lett 2020 Oct 21;331:92-101. Epub 2020 May 21.

Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China. Electronic address:

Aflatoxin G (AFG) is a member of the carcinogenic aflatoxin family. Our previous studies indicated that oral administration of AFG caused tumor necrosis factor (TNF)-α-dependent inflammation that enhanced oxidative DNA damage in alveolar epithelial cells, which may be related to AFG-induced lung carcinogenesis. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein; the intracellular and extracellular roles of HMGB1 have been shown to contribute to DNA repair and sterile inflammation. The role of HMGB1 in DNA damage in an aflatoxin-induced lung inflammatory environment was investigated in this study. Upregulation of HMGB1, TLR2, and RAGE was observed in AFG-induced lung inflamed tissues and adenocarcinoma. Blocking AFG-induced inflammation by neutralization of TNF-α inhibited the upregulation of HMGB1 in mouse lung tissues, suggesting that AFG-induced TNF-α-dependent inflammation regulated HMGB1 expression. In the in vitro human pulmonary epithelial cell line model, Beas-2b, AFG directly enhanced the cytosolic translocation of HMGB1 and its extracellular secretion. The addition of extracellular soluble HMGB1 protected AFG-induced DNA damage through the TLR2/NF-κB pathway in Beas-2b cells. In addition, blockade of endogenous HMGB1 by siRNA significantly enhanced AFG-induced damage. Thus, our findings showed that both extracellularly-released and nuclear and cytosolic HMGB1 could protect the cell from AFG-induced cell damage in a TNF-α-dependent lung inflammatory environment.
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http://dx.doi.org/10.1016/j.toxlet.2020.05.013DOI Listing
October 2020

EGFR-ERK pathway regulates CSN6 to contribute to PD-L1 expression in glioblastoma.

Mol Carcinog 2020 05 5;59(5):520-532. Epub 2020 Mar 5.

Laboratory of Pathology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.

Glioblastoma (GBM) is the most common and malignant brain tumor in adults. Recently, programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockades have been applied for GBM treatment. However, the mechanism of PD-L1 upregulation in GBM is still unclear. COP9 signalosome 6 (CSN6) is crucial for maintaining the protein stabilization in cancer cells. In this study, we applied human GBM specimens and cell lines to investigate whether the EGFR-ERK pathway regulates CSN6 for PD-L1 upregulation. Data from The Cancer Genome Atlas dataset showed that high expression of EGFR, CSN6, and PD-L1 in patients with glioma was associated with poor prognosis. In 47 human GBM specimens, high expression of PD-L1 was associated with low amount of CD8 T cell infiltration as well as the poor prognosis of patients. CSN6 was positively correlated with EGFR and PD-L1 expression in human GBM specimens. We treated two GBM cell lines (U87 and U251) with epidermal growth factor (EGF) in vitro, and found EGF-upregulated p-EGFR, p-ERK, CSN6, and PD-L1 expression in GBM cells. PD98059, the ERK blocker, inhibited upregulations of CSN6 and PD-L1 in EGF-treated cells. Inhibition of CSN6 by small interfering RNA decreased PD-L1 expression but also increased CHIP expression in GBM cells. When the cells were treated with EGF and cycloheximide (CHX), a protein synthesis inhibitor, EGF-reduced CHX-induced CSN6 and PD-L1 turnover in GBM cells. Furthermore, CSN6-mediated downregulation of PD-L1 was inhibited by MG132, a proteasome inhibitor in U87 cells. Thus, these results suggest that the EGFR-ERK pathway may upregulate CSN6, which may inhibit PD-L1 degradation and subsequently maintain PD-L1 stability in GBM.
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http://dx.doi.org/10.1002/mc.23176DOI Listing
May 2020

Cationic Copolymerization of Isobutylene with 4-Vinylbenzenecyclobutylene: Characteristics and Mechanisms.

Polymers (Basel) 2020 Jan 13;12(1). Epub 2020 Jan 13.

Beijing Key Lab of Special Elastomeric Composite Materials, Department of Materials Science and Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, China.

A random copolymer of isobutylene (IB) and 4-vinylbenzenecyclobutylene (4-VBCB) was synthesized by cationic polymerization at -80 °C using 2-chloro-2,4,4-trimethylpentane (TMPCl) as initiator. The laws of copolymerization were investigated by changing the feed quantities of 4-VBCB. The molecular weight of the copolymer decreased, and its molecular weight distribution (MWD) increased with increasing 4-VBCB content. We proposed a possible copolymerization mechanism behind the increase in the chain transfer reaction to 4-VBCB with increasing of feed quantities of 4-VBCB. The thermal properties of the copolymers were studied by solid-phase heating and crosslinking. After crosslinking, the decomposition and glass transition temperatures () of the copolymer increased, the network structure that formed did not break when reheated, and the mechanical properties remarkably improved.
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http://dx.doi.org/10.3390/polym12010201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023408PMC
January 2020

Genetic diversity, phylogenetic structure and development of core collections in Melilotus accessions from a Chinese gene bank.

Sci Rep 2019 09 10;9(1):13017. Epub 2019 Sep 10.

State Key Laboratory of Grassland Agro-ecosystems; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs; College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, P.R. China.

Melilotus is an important forage legume, with high values as feed and medicine, and widely used as green manure, honey plant, and wildlife habitat enhancer. The genetic diversity, structure and subdivision of this forage crop remain unclear, and plant genetic resources are the basis of biodiversity and ecosystem diversity and have attracted increasing attention. In this study, the whole collection of 573 accessions from the National Gene Bank of Forage Germplasm (NGBFG, China) and 48 accessions from the National Plant Germplasm System (NPGS, USA) in genus Melilotus were measured with respect to five seed characters: seed length, width, width-to-length ratio, circumference and 100-seed weight. Shannon' genetic diversity index (H') and phenotypic differentiation (Pst) were calculated to better describe the genetic diversity. The ITS and matK sequences were used to construct phylogenetic trees and study the genetic relationships within genus Melilotu. Based on seed morphology and molecular marker data, we preliminarily developed core collections and the sampling rates of M. albus and M. officinalis were determined to be 15% and 25%, respectively. The results obtained here provide preliminary sorting and supplemental information for the Melilotus collections in NGBFG, China, and establish a reference for further genetic breeding and other related projects.
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http://dx.doi.org/10.1038/s41598-019-49355-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736865PMC
September 2019

Enhancement of Dielectric Performance of Polymer Composites via Constructing BaTiO-Poly(dopamine)-Ag Nanoparticles through Mussel-Inspired Surface Functionalization.

ACS Omega 2018 Oct 25;3(10):14087-14096. Epub 2018 Oct 25.

Department of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

We demonstrate the synthesis of a novel core-satellite-structured BaTiO-poly(dopamine)-silver (BT-PDA-Ag) nanoparticle for improving dielectric properties of nitrile-butadiene rubber (NBR) nanocomposites. The BT-PDA-Ag nanoparticles are synthesized by dopamine oxidative polymerization and electroless plating of silver. The Ag nanoparticles decorated on the BT nanoparticles enhanced the dielectric constant of NBR nanocomposites due to the increased conductivity of the filler/matrix interlayer and nanocapacitor structure. In addition, the incorporation of the BT nanoparticles prevented the continuous connection of Ag nanoparticles and suppressed the formation of a conductive path in the NBR matrix. Moreover, the ultrasmall Ag nanoparticles trapped the carriers by Coulomb blockade and quantum confinement effects, which results in low dielectric loss and electrical conductivity of nanocomposites. The proposed method with simplicity and scalability can be adapted to process high-dielectric polymer nanocomposites.
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http://dx.doi.org/10.1021/acsomega.8b02367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644546PMC
October 2018

Melatonin suppresses milk fat synthesis by inhibiting the mTOR signaling pathway via the MT1 receptor in bovine mammary epithelial cells.

J Pineal Res 2019 Oct 23;67(3):e12593. Epub 2019 Jul 23.

College of Animal Science and Technology, Northwest A&F University, Yangling, China.

Milk fat content is an important criterion for assessing milk quality and is one of the main target traits of dairy cattle breeding. Recent studies have shown the importance of melatonin in regulating lipid metabolism, but the potential effects of melatonin on milk fat synthesis in bovine mammary epithelial cells (BMECs) remain unclear. Here, we showed that melatonin supplementation at 10 μmol/L significantly downregulated the mRNA expression of lipid metabolism-related genes and resulted in lower lipid droplet formation and triglyceride accumulation. Moreover, melatonin significantly upregulated melatonin receptor subtype melatonin receptor 1a (MT1) gene expression, and the negative effects of melatonin on milk fat synthesis were reversed by treatment with the nonselective MT1/melatonin receptor subtype melatonin receptor 1b (MT2) antagonist. However, a selective MT2 antagonist did not modify the negative effects of melatonin on milk fat synthesis. In addition, KEGG analysis revealed that melatonin inhibition of milk fat synthesis may occur via the mTOR signaling pathway. Further analysis revealed that melatonin significantly suppressed the activation of the mTOR pathway by restricting the phosphorylation of mTOR, 4E-BP1, and p70S6K, and the inhibition of melatonin on milk fat synthesis was reversed by mTOR activator MHY1485 in BMECs. Furthermore, in vivo experiments in Holstein dairy cows showed that exogenous melatonin significantly decreased milk fat concentration. Our data from in vitro and in vivo studies revealed that melatonin suppresses milk fat synthesis by inhibiting the mTOR signaling pathway via the MT1 receptor in BMECs. These findings lay a foundation to identify a new potential means for melatonin to modulate the fat content of raw milk in Holstein dairy cows.
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http://dx.doi.org/10.1111/jpi.12593DOI Listing
October 2019

Bta-miR-34b regulates milk fat biosynthesis by targeting mRNA decapping enzyme 1A (DCP1A) in cultured bovine mammary epithelial cells1.

J Anim Sci 2019 Sep;97(9):3823-3831

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P.R. China.

Milk fat is a main nutritional component of milk, and it has become one of the important traits of dairy cow breeding. Recently, there is increasing evidence that microRNAs (miRNA) play significant roles in the process of milk fat synthesis in the mammary gland. Primary bovine mammary epithelial cells (BMEC) were harvested from midlactation cows and cultured in DMEM/F-12 medium with 10% fetal bovine serum, 100 units/mL penicillin, 100 µg/mL streptomycin, 5 µg/mL bovine insulin, 1 µg/mL hydrocortisone, and 2 µg/mL bovine prolactin. We found that miR-34b mimic transfection in BMEC reduced the content of intracellular triacylglycerol (TAG) and lipid droplet accumulation via triacylglycerol assay and Oil Red O staining; meanwhile, overexpression of miR-34b inhibited mRNA expression of lipid metabolism-related genes such as peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), and CCAAT enhancer binding protein alpha (C/EBPα). Whereas miR-34b inhibitor resulted in completely opposite results. Furthermore, q-PCR and western blot analysis revealed the mRNA and protein expression levels of DCP1A were downregulated in miR-34b mimic transfection group and upregulated in miR-34b inhibitor group. Moreover, luciferase reporter assays verified that DCP1A was the direct target of miR-34b and DCP1A gene silencing in BMEC-inhibited TAG accumulation and suppressed lipid droplet formation. In conclusion, these findings revealed a novel miR-34b-DCP1A axis that has a significant role in regulating milk fat synthesis and suggested that miR-34b may be used to improve the beneficial ingredients in milk.
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http://dx.doi.org/10.1093/jas/skz230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735825PMC
September 2019

Fatty acid-binding protein 1 increases steer fat deposition by facilitating the synthesis and secretion of triacylglycerol in liver.

PLoS One 2019 22;14(4):e0214144. Epub 2019 Apr 22.

College of Animal Science and Technology, Northwest A & F University, Yangling, Shaanxi, China.

Castration is an important means of improving the beef quality via increasing fat deposition. However, little is known about the molecular mechanism underlying the fat deposition after castration. Here, the intramuscular fat (IMF) content of the steer group was shown to be much higher than the bull group. To understand transcriptional changes in the genes involved in fat deposition following castration, differential expression patterns of mRNAs in liver tissue were investigated in steers and bulls using RNA sequencing. In total, we obtained 58,282,367-54,918,002 uniquely mapped reads, which covered 90.13% of the currently annotated transcripts; 5,864 novel transcripts and optimized 9,088 known genes were determined. These results indicated that castration could change the expression patterns of mRNAs in liver tissue, and 282 differentially expressed genes (DEGs) were detected between steers and bulls. KEGG pathway analysis showed that the DEGs were mostly enriched in PPAR signaling pathway, steroid biosynthesis, steroid hormone biosynthesis, and biosynthesis of fatty acids. Furthermore, eight DEGs were corroborated via quantitative real-time PCR and we found that FABP1 gene knockdown in bovine hepatocytes prominently reduced intracellular triacylglycerol (TAG) synthesis and very low density lipoprotein (VLDL) secretion in culture medium. In summary, these results indicate that FABP1 may promote fat deposition by promoting the production and secretion of TAG and VLDL in steer liver.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214144PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476475PMC
December 2019

Characteristics and Mechanism of Vinyl Ether Cationic Polymerization in Aqueous Media Initiated by Alcohol/B(C₆F₅)₃/Et₂O.

Polymers (Basel) 2019 Mar 14;11(3). Epub 2019 Mar 14.

College of Material Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

Aqueous cationic polymerizations of vinyl ethers (isobutyl vinyl ether (IBVE), 2-chloroethyl vinyl ether (CEVE), and -butyl vinyl ether (-BVE)) were performed for the first time by a CumOH/B(C₆F₅)₃/Et₂O initiating system in an air atmosphere. The polymerization proceeded in a reproducible manner through the careful design of experimental conditions (adding initiator, co-solvents, and surfactant or decreasing the reaction temperature), and the polymerization characteristics were systematically tested and compared in the suspension and emulsion. The significant difference with traditional cationic polymerization is that the polymerization rate in aqueous media using B(C₆F₅)₃/Et₂O as a co-initiator decreases when the temperature is lowered. The polymerization sites are located on the monomer/water surface. Density functional theory (DFT) was applied to investigate the competition between H₂O and alcohol combined with B(C₆F₅)₃ for providing a theoretical basis. The effectiveness of the proposed mechanism for the aqueous cationic polymerization of vinyl ethers using CumOH/B(C₆F₅)₃/Et₂O was confirmed.
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http://dx.doi.org/10.3390/polym11030500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473351PMC
March 2019

Improved Mechanical and Electrochemical Properties of XNBR Dielectric Elastomer Actuator by Poly(dopamine) Functionalized Graphene Nano-Sheets.

Polymers (Basel) 2019 Jan 27;11(2). Epub 2019 Jan 27.

Department of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

In this work, graphene nano-sheets (GNS) functionalized with poly(dopamine) (PDA) (denoted as GNS-PDA) were dispersed in a carboxylated nitrile butadiene rubber (XNBR) matrix to obtain excellent dielectric composites via latex mixing. Because hydrogen bonds were formed between ⁻COOH groups of XNBR and phenolic hydroxyl groups of PDA, the encapsulation of GNS-PDA around XNBR latex particles was achieved, and led to a segregated network structure of filler formed in the GNS-PDA/XNBR composite. Thus, the XNBR composite filled with GNS-PDA showed improved filler dispersion, enhanced dielectric constant and dielectric strength, and decreased conductivity compared with the XNBR composite filled with pristine GNS. Finally, the GNS-PDA/XNBR composite displayed an actuated strain of 2.4% at 18 kV/mm, and this actuated strain was much larger than that of pure XNBR (1.3%) at the same electric field. This simple, environmentally friendly, low-cost, and effective method provides a promising route for obtaining a high-performance dielectric elastomer with improved mechanical and electrochemical properties.
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http://dx.doi.org/10.3390/polym11020218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419049PMC
January 2019

Excitons and Biexciton Dynamics in Single CsPbBr Perovskite Quantum Dots.

J Phys Chem Lett 2018 Dec 30;9(24):6934-6940. Epub 2018 Nov 30.

State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Laser Spectroscopy , Shanxi University , Taiyuan 030006 , People's Republic of China.

Colloidal lead halide perovskite quantum dots, due to their optical versatility and facile solution processability, have been recently recognized as components of various optoelectronic devices. Detailed understanding of their exciton recombination dynamics at the single-particle level is necessary for utilizing their full potential. We conducted spectroscopic studies of the excitons and biexciton dynamics in single CsPbBr perovskite quantum dots. It was found that while the rates of radiative recombination remain essentially constant, the overall relaxation process is dominated by nonradiative recombination of single excitons and biexcitons. The radiative lifetime scaling is determined to be ∼1.0 for single exciton and ∼4.4 for biexcitons. A linear dependence of fluorescence lifetime vs intensity distribution agrees well with the prediction of the model of multiple recombination centers. The blinking mechanism of CsPbBr quantum dots is addressed by considering the trion states under higher excitation powers.
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http://dx.doi.org/10.1021/acs.jpclett.8b03098DOI Listing
December 2018

Distinct Iron Deposition Profiles of Liver Zones in Various Models with Iron Homeostasis Disorders.

Adv Sci (Weinh) 2018 Nov 12;5(11):1800866. Epub 2018 Oct 12.

State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085 China.

Determination of iron accumulation is crucial in diagnosing the occurrence and progression of many liver- and iron-related diseases. Thus far, little is known about the profiles of iron deposition in different liver zones, particularly under conditions with disordered iron homeostasis. Here, uneven iron distribution in livers of patients with hereditary hemochromatosis (HH) is uncovered, showing the region with the highest iron concentration near the entrance site of the portal vein and hepatic artery in contrast to the sites with the lowest iron concentration close to the distal edge. Distinct iron distribution profiles are also found throughout liver zones in wild-type mice and various mouse models with iron metabolism disorders, including hemochromatosis ), iron deficiency, and inflammation. Of note, similar findings observed in HH patients are further demonstrated in mice. Moreover, the zones with greater iron accumulation appear to be more sensitive to iron changes, e.g., there is iron increase upon iron overload and iron loss in response to iron deficiency. Mechanistic investigation manifests that these differential iron changes in liver zones are subjected to the regulation by the hepcidin-ferroportin axis. Additionally, the data corroborate the reliability of magnetic resonance imaging (MRI) in recognizing the differential iron deposition profiles among liver zones.
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http://dx.doi.org/10.1002/advs.201800866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247051PMC
November 2018

Genetic variation and diversity in 199 Melilotus accessions based on a combination of 5 DNA sequences.

PLoS One 2018 13;13(3):e0194172. Epub 2018 Mar 13.

State Key Laboratory of Grassland Agro-ecosystems; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture; College of Pastoral Agriculture Science and Technology, Lanzhou University; Lanzhou, China.

Melilotus is an important genus of legume plants and an herbage with excellent nitrogen fixation; it can tolerate extreme environmental conditions and possesses important medicinal value. However, there is limited genetic information about the genus; thus, we analysed four chloroplast loci (rbcL, matK, psbA-trnH and trnL-F) and one nuclear region (ITS) to determine the genetic diversity of 199 accessions from 18 Melilotus species. The rbcL and matK sequences were highly conserved, whereas the trnL-F and ITS sequences contained variable and parsimony-informative sites. In our analyses of the single and combined regions, we calculated the pairwise distance, haplotype and nucleotide diversity and gaps and then constructed phylogenetic trees to assess the genetic diversity, and our results revealed significant variations among the different accessions. The genetic distance values were between zero and nine, and based on the combined regions, the highest frequency value was approximately four. Melilotus showed high haplotype and nucleotide diversity, particularly in the ITS sequences, with values of 0.86 and 0.0087, respectively. The single ITS sequence, psbA-trnH, and the combined matK+rbcL+trnL-F (MRT) and matK+rbcL+psbA-trnH+trnL-F+ITS (MRPTI) regions showed interspecific variation in the gap analysis. Phylogenetic trees calculated using ITS, psbA-trnH and MRPTI sequences indicated distinct genetic relationship in 18 species, and these species could be divided into two groups. By determining the genetic diversity of plants, we can evaluate the genetic relationships among species and accessions, providing a basis for preserving and utilizing the genetic resources of Melilotus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194172PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849350PMC
June 2018

Investigation of the interactions between 1-butyl-3-methylimidazolium-based ionic liquids and isobutylene using density functional theory.

J Mol Model 2018 Mar 6;24(4):83. Epub 2018 Mar 6.

Department of Materials Science and Engineering, Beijing Institute of Petrochemical Technology, Beijing, 102617, China.

To identify ionic liquids (ILs) that could be used as solvents in isobutylene (IB) polymerization, the interactions between IB and eight different ILs based on the 1-butyl-3-methylimidazolium cation ([Bmim]) were investigated using density functional theory (DFT). The anions in the ILs were chloride, hexafluorophosphate, tetrafluoroborate, bis[(trifluoromethyl)sulfonyl]imide, tetrachloroaluminate ([AlCl]), tetrachloroferrate, acetate, and trifluoroacetate. The interaction geometries were explained by changes in the total energy, intermolecular distances, Hirshfeld charges, and the electrostatic potential surface. The IL solvents were screened by comparing their interaction intensities with IB to the interaction intensities of reference ILs ([AlCl]-based ILs) with IB. The microscopic mechanism for IB dissolution was rationalized by invoking a previously reported microscopic mechanism for the dissolution of gases in ILs. Computation results revealed that hydrogen (H) bonding between C2-H on the imidazolium ring and the anions plays a key role in ion pair (IP) formation. The addition of IB leads to slight changes in the dominant interactions of the IP. IB molecules occupied cavities created by small angular rearrangements of the anions, just as CO does when it is dissolved in an IL. The limited total free space in the ILs and the much larger size of IB than CO were found to be responsible for the poor solubility of IB compared with that of CO in the ILs.
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http://dx.doi.org/10.1007/s00894-018-3586-yDOI Listing
March 2018

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel.

Int J Nanomedicine 2017 13;12:8779-8799. Epub 2017 Dec 13.

Push-Kang Biotechnology, Hangzhou.

Purpose: Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)--poly (d,l-lactide) (mPEG-PDLLA).

Methods: PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated.

Results: The size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was -19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications.

Conclusion: These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.
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http://dx.doi.org/10.2147/IJN.S150196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732553PMC
May 2018

Potential DNA barcodes for Melilotus species based on five single loci and their combinations.

PLoS One 2017 14;12(9):e0182693. Epub 2017 Sep 14.

State Key Laboratory of Grassland Agro-ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, China.

Melilotus, an annual or biennial herb, belongs to the tribe Trifolieae (Leguminosae) and consists of 19 species. As an important green manure crop, diverse Melilotus species have different values as feed and medicine. To identify different Melilotus species, we examined the efficiency of five candidate regions as barcodes, including the internal transcribed spacer (ITS) and two chloroplast loci, rbcL and matK, and two non-coding loci, trnH-psbA and trnL-F. In total, 198 individuals from 98 accessions representing 18 Melilotus species were sequenced for these five potential barcodes. Based on inter-specific divergence, we analysed sequences and confirmed that each candidate barcode was able to identify some of the 18 species. The resolution of a single barcode and its combinations ranged from 33.33% to 88.89%. Analysis of pairwise distances showed that matK+rbcL+trnL-F+trnH-psbA+ITS (MRTPI) had the greatest value and rbcL the least. Barcode gap values and similarity value analyses confirmed these trends. The results indicated that an ITS region, successfully identifying 13 of 18 species, was the most appropriate single barcode and that the combination of all five potential barcodes identified 16 of the 18 species. We conclude that MRTPI is the most effective tool for Melilotus species identification. Taking full advantage of the barcode system, a clear taxonomic relationship can be applied to identify Melilotus species and enhance their practical production.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182693PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598934PMC
October 2017

Value and Clinical Application of Orthopedic Metal Artifact Reduction Algorithm in CT Scans after Orthopedic Metal Implantation.

Korean J Radiol 2017 May-Jun;18(3):526-535. Epub 2017 Apr 3.

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province 110004, China.

Objective: To evaluate orthopedic metal artifact reduction algorithm (O-MAR) in CT orthopedic metal artifact reduction at different tube voltages, identify an appropriate low tube voltage for clinical practice, and investigate its clinical application.

Materials And Methods: The institutional ethical committee approved all the animal procedures. A stainless-steel plate and four screws were implanted into the femurs of three Japanese white rabbits. Preoperative CT was performed at 120 kVp without O-MAR reconstruction, and postoperative CT was performed at 80-140 kVp with O-MAR. Muscular CT attenuation, artifact index (AI) and signal-to-noise ratio (SNR) were compared between preoperative and postoperative images (unpaired test), between paired O-MAR and non-O-MAR images (paired Student test) and among different kVp settings (repeated measures ANOVA). Artifacts' severity, muscular homogeneity, visibility of inter-muscular space and definition of bony structures were subjectively evaluated and compared (Wilcoxon rank-sum test). In the clinical study, 20 patients undertook CT scan at low kVp with O-MAR with informed consent. The diagnostic satisfaction of clinical images was subjectively assessed.

Results: Animal experiments showed that the use of O-MAR resulted in accurate CT attenuation, lower AI, better SNR, and higher subjective scores ( < 0.010) at all tube voltages. O-MAR images at 100 kVp had almost the same AI and SNR as non-O-MAR images at 140 kVp. All O-MAR images were scored ≥ 3. In addition, 95% of clinical CT images performed at 100 kVp were considered satisfactory.

Conclusion: O-MAR can effectively reduce orthopedic metal artifacts at different tube voltages, and facilitates low-tube-voltage CT for patients with orthopedic metal implants.
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http://dx.doi.org/10.3348/kjr.2017.18.3.526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390622PMC
October 2017

Carbon Nanotubes Disrupt Iron Homeostasis and Induce Anemia of Inflammation through Inflammatory Pathway as a Secondary Effect Distant to Their Portal-of-Entry.

Small 2017 04 13;13(15). Epub 2017 Feb 13.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.

Although numerous toxicological studies have been performed on carbon nanotubes (CNTs), a few studies have investigated their secondary and indirect effects beyond the primary target tissues/organs. Here, a cascade of events are investigated: the initiating event and the subsequent key events necessary for the development of phenotypes, namely CNT-induced pro-inflammatory effects on iron homeostasis and red blood cell formation, which are linked to anemia of inflammation (AI). A panel of CNTs are prepared including pristine multiwall CNTs (P-MWCNTs), aminated MWCNTs (MWCNTs-NH ), polyethylene glycol MWCNTs (MWCNTs-PEG), polyethyleneimine MWCNTs (MWCNTs-PEI), and carboxylated MWCNTs (MWCNTs-COOH). It has been demonstrated that all CNT materials provoke inflammatory cytokine interleukin-6 (IL-6) production and stimulate hepcidin induction, associated with disordered iron homeostasis, irrespective of exposure routes including intratracheal, intravenous, and intraperitoneal administration. Meanwhile, PEG and COOH modifications can ameliorate the activation of IL-6-hepcidin signaling. Long-term exposure of MWCNTs results in AI and extramedullary erythropoiesis. Thus, an adverse outcome pathway is identified: MWCNT exposure leads to inflammation, hepatic hepcidin induction, and disordered iron metabolism. Together, the combined data depict the hazardous secondary toxicity of CNTs in incurring anemia through inflammatory pathway. This study will also open a new avenue for future investigations on CNT-induced indirect and secondary adverse effects.
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http://dx.doi.org/10.1002/smll.201603830DOI Listing
April 2017

Icariin regulates systemic iron metabolism by increasing hepatic hepcidin expression through Stat3 and Smad1/5/8 signaling.

Int J Mol Med 2016 May 1;37(5):1379-88. Epub 2016 Apr 1.

Department of Cardiovascular Diseases, Beijing Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, P.R. China.

Systemic iron homeostasis is strictly controlled under normal conditions to ensure a balance between the absorption, utilization, storage and recycling of iron. The hepcidin-ferroportin (FPN) axis is of critical importance in the maintenance of iron homeostasis. Hepcidin deficiency gives rise to enhanced dietary iron absorption, as well as to increased iron release from macrophages, and this in turn results in iron accumulation in the plasma and organs, and is associated with a range of tissue pathologies. Low hepcidin levels have been demonstrated in most forms of hereditary hemochromatosis (HH), as well as in β-thalassemia. Therapies that increase hepcidin concentrations may potentially play a role in the treatment of these iron overload-related diseases. To date, natural compounds have not been extensively investigated for this purpose, to the best of our knowledge. Thus, in the present study, we screened natural compounds that have the potential to regulate hepcidin expression. By performing hepcidin promoter-luciferase assay, RT-qPCR and animal experiments, we demonstrated that icariin and berberine were potent stimulators of hepcidin transcription. Mechanistic experiments indicated that icariin and berberine increased hepcidin expression by activating the signal transducer and activator of transcription 3 (Stat3) and Smad1/5/8 signaling pathways. The induction of hepcidin was confirmed in mice following icariin administration, coupled with associated changes in serum and tissue iron concentrations. In support of these findings, the icariin analogues, epimedin A, B and C, also increased hepatic hepcidin expression. However, these changes were not observed in hepcidin-deficient [Hamp1-/- or Hamp1‑knockout (KO)] mice following icariin administration, thereby verifying hepatic hepcidin as the target of icariin. Although berberine exhibited a robust capacity to promote hepcidin expression in vitro, it failed to alter hepcidin expression in mice. Taken together, the findings of the present study suggest that icariin exhibits a robust capacity to increase hepatic hepcidin expression and to modulate systemic iron homeostasis. The present study therefore highlights the significance of using natural compounds to ameliorate iron disorders through the regulation of hepcidin expression.
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http://dx.doi.org/10.3892/ijmm.2016.2545DOI Listing
May 2016

Self-Passivation of Defects: Effects of High-Energy Particle Irradiation on the Elastic Modulus of Multilayer Graphene.

Adv Mater 2015 Nov 5;27(43):6841-7. Epub 2015 Oct 5.

Department of Materials Science and Engineering, University of California, Berkeley, CA, 94706, USA.

The elastic modulus of multilayer graphene is found to be more robust to damage created by high-energy α-particle irradiation as compared to monolayer graphene. Theoretical analysis indicates that irradiation of multilayer graphene generates interlayer links that potentially increase the stiffness of the multilayer by passivating local defects.
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http://dx.doi.org/10.1002/adma.201501752DOI Listing
November 2015

Disruption of iron homeostasis and resultant health effects upon exposure to various environmental pollutants: A critical review.

J Environ Sci (China) 2015 Aug 25;34:155-64. Epub 2015 May 25.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address:

Environmental pollution has become one of the greatest problems in the world, and the concerns about environmental pollutants released by human activities from agriculture and industrial production have been continuously increasing. Although intense efforts have been made to understand the health effects of environmental pollutants, most studies have only focused on direct toxic effects and failed to simultaneously evaluate the long-term adaptive, compensatory and secondary impacts on health. Burgeoning evidence suggests that environmental pollutants may directly or indirectly give rise to disordered element homeostasis, such as for iron. It is crucially important to maintain concerted cellular and systemic iron metabolism. Otherwise, disordered iron metabolism would lead to cytotoxicity and increased risk for various diseases, including cancers. Thus, study on the effects of environmental pollutants upon iron homeostasis is urgently needed. In this review, we recapitulate the available findings on the direct or indirect impacts of environmental pollutants, including persistent organic pollutants (POPs), heavy metals and pesticides, on iron homeostasis and associated adverse health problems. In view of the unanswered questions, more efforts are warranted to investigate the disruptive effects of environmental pollutants on iron homeostasis and consequent toxicities.
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http://dx.doi.org/10.1016/j.jes.2015.04.004DOI Listing
August 2015

An important role of the hepcidin-ferroportin signaling in affecting tumor growth and metastasis.

Acta Biochim Biophys Sin (Shanghai) 2015 Sep 22;47(9):703-15. Epub 2015 Jul 22.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China

Epidemiological and experimental studies have suggested that deregulated hepcidin-ferroportin (FPN) signaling is associated with the increased risk of cancers. However, the effects of deregulated hepcidin-FPN signaling on tumor behaviors such as metastasis and epithelial to mesenchymal transition (EMT) have not been closely investigated. In this study, LL/2 cancer cells were found to exhibit an impaired propensity to home into lungs, and a reduced ability to develop tumors was also demonstrated in lungs of Hamp1(-/-) mice. Moreover, hepatic hepcidin deficiency was found to considerably favor tumor-free survival in Hamp1(-/-) mice, compared with wild-type mice. These data thus underscored a contributive role of hepatic hepcidin in promoting lung cancer cell homing and fostering tumor progression. To explore the role of FPN in regulating tumor progression, we genetically engineered 4T1 cells with FPN over-expression upon induction by doxycycline. With this cell line, it was discovered that increased FPN expression reduced cell division and colony formation in vitro, without eliciting significant cell death. Analogously, FPN over-expression impeded tumor growth and metastasis to lung and liver in mice. At the molecular level, FPN over-expression was identified to undermine DNA synthesis and cell cycle progression. Importantly, FPN over-expression inhibited EMT, as reflected by the significant decrease of representative EMT markers, such as Snail1, Twist1, ZEB2, and vimentin. Additionally, there was also a reduction of lactate production in cells upon induction of FPN over-expression. Together, our results highlighted a crucial role of the hepcidin-FPN signaling in modulating tumor growth and metastasis, providing new evidence to understand the contribution of this signaling in cancers.
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http://dx.doi.org/10.1093/abbs/gmv063DOI Listing
September 2015