Publications by authors named "Limin Han"

42 Publications

Analysis on the structure effect of marine fishery total factor productivity under high-quality development in China.

PLoS One 2021 24;16(11):e0259853. Epub 2021 Nov 24.

Shandong Foreign Trade Vocational College, Qingdao, Shandong, China.

Improving total factor productivity (TFP) is the source of power for high-quality development. Industrial structure optimization is an important way to improve TFP. This paper constructed an econometric model of industry structure changes impacting on TFP in the marine fisheries and conducted an empirical test and analysis. The results showed that the industry rationalization, softening and processing coefficient of marine fishery had a significant "structural dividend" for improving its TFP; while the impact of industrial structure advancement and aquaculture-catching structure changes did not have "structural dividend", but it could be a combination of other factors to reduce these adverse effects.We believe that simply pursuing the advanced evolution of the industrial structure is not conducive to sustainable development of fishery. Under the pursuit of the rationalization of the marine fishery industry structure, by promoting the coordinated evolution of marine fisheries advancement, aquaculture-catching structure and other factors, the "structural dividend" effect can be enhanced and the fishery can achieve sustainable development. Finally, it proposed to promote the development of advancement and rationalization of marine fishery industry structure coordinately, adjust fishery science and technology transformation direction and key points, and accelerate the development of intensive processing industry by cross-border integration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612771PMC
November 2021

A General Route of Using Lignite Depolymerized Derivatives for Catalyst Construction: Insights into the Effects of the Derivative Structures and Solvents.

ACS Omega 2021 Jun 4;6(23):14926-14937. Epub 2021 Jun 4.

Chemical Engineering, Inner Mongolia University of Technology; Inner Mongolia Key Laboratory of High-Value Functional Utilization of Low Rank Carbon Resources, Hohhot 010051, Inner Mongolia, China.

Depolymerization is an emerging and promising route for the value-added utilization of low-rank coal (LRC) resources, and how to use the complex depolymerized mixtures efficiently is of great importance for this route. In this work, we designed the rational route of using depolymerized mixtures from lignite ruthenium ion-catalyzed oxidation (RICO) depolymerization directly without complex separation to construct a Zr-based hydrogenation catalyst. The prepared catalyst was applied into the catalytic transfer hydrogenation of biomass-derived carbonyl compounds. Meanwhile, a copper-based oxidation catalyst was also constructed via a similar route to investigate the universality of the proposed route. Special insights were given into how the depolymerized components with different structures influenced the performances of the catalysts. The effects of the solvents used during the catalyst preparation (HO and DMF) were also studied. The results showed that the proposed route using the depolymerized mixtures from lignite RICO to construct catalysts was feasible for both Zr-based and Cu-based catalysts. The two catalysts prepared gave high efficiency for their corresponding reaction, , the Zr-based catalyst for catalytic transfer hydrogenation of biomass-derived carbonyl compounds and the Cu-based catalyst for selective oxidation of alcohols into aldehydes. Different depolymerized components contributed differently to the activity of the catalyst, and the solvents during the preparation process could also influence the activity of the catalyst. The depolymerized components and the solvents influenced the activities of the Zr-based catalyst mainly changing the Zr contents, the microenvironment of Zr, and the specific areas of the catalyst.
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http://dx.doi.org/10.1021/acsomega.1c00766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209817PMC
June 2021

Correction to: HnRNP F/H associate with hTERC and telomerase holoenzyme to modulate telomerase function and promote cell proliferation.

Cell Death Differ 2021 May 27. Epub 2021 May 27.

Peking University Research Center on Aging, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University, 100191, Beijing, China.

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http://dx.doi.org/10.1038/s41418-021-00806-yDOI Listing
May 2021

MiR-365a-3p-Mediated Regulation of HELLS/GLUT1 Axis Suppresses Aerobic Glycolysis and Gastric Cancer Growth.

Front Oncol 2021 15;11:616390. Epub 2021 Mar 15.

Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.

Gastric cancer (GC) is a common and invasive malignancy, which lacks effective treatment and is the third main reason of cancer death. Metabolic reprogramming is one of the main reasons that GC is difficult to treat in various environments. Particularly, abnormal glycolytic activity is the most common way of metabolism reprogramming in cancer cells. Numerous studies have shown that microRNAs play important roles in reprogramming glucose metabolism. Here, we found a microRNA-miR-365a-3p, was significantly downregulated in GC according to bioinformatics analysis. Low expression of miR-365a-3p correlated with poor prognosis of GC patients. Overexpression of miR-365a-3p in GC cells significantly inhibited cell proliferation by inducing cell cycle arrest at G1 phase. Notably, miR-365a-3p induced downregulation of HELLS through binding to its 3' untranslated region (UTR). Additionally, we found that miR-365a-3p suppressed aerobic glycolysis by inhibiting HELLS/GLUT1 axis. Lastly, we shown that overexpression of miR-365a-3p significantly inhibited tumor growth in nude mice. Conversely, Reconstituted the expression of HELLS rescued the suppressive effects of miR-365a-3p. Our data collectively indicated that miR-365a-3p functioned as a tumor suppressor in GC through downregulating HELLS. Therefore, targeting of the novel miR-365a-3p/HELLS axis could be a potentially effective therapeutic approach for GC.
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http://dx.doi.org/10.3389/fonc.2021.616390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005720PMC
March 2021

A Multi-response Aluminum Metal-organic Frameworks for Fluorescence Sensing of Fe, Sr, SiOand Toluene.

Methods Appl Fluoresc 2021 Apr 1;9(2). Epub 2021 Apr 1.

Department of Chemistry, Baotou Teachers' College, Baotou, People's Republic of China.

A new Aluminum metal-organic frameworks(Al-MOF) based on tricarboxylate ligands(L){L = 2,2',2'-([1,3,5]-triazine-2,4,6-triimino)tribenzoic acid)} has been designed and synthesized. It can be served as a platform of multi-responsive fluorescence sensor for Fe, Srand SiOin water, which is mainly due to the significant enhancement effect of these ions on the fluorescence intensity of Al-MOF. Especially, Feions are rarely able to induce MOFs fluorescence enhancement. The limit of detection for three kinds of ions is 6.62* 10M, 5.37* 10M, 6.85* 10M respectively. Meanwhile, It can also be used as a multi-response fluorescence probe to detect toluene in DMF solution, limit of detection is 9.16* 10M respectively. The structure of Al-MOF was characterized by FTIR,H NMR, SEM, TAG, PXRD and element analysis. The PXRD showed that the structure of Al-MOF remained the high water stability and pH stability. The application of water samples and vegetables showed that Al-MOF had high sensitive detection for Feions.
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http://dx.doi.org/10.1088/2050-6120/abf027DOI Listing
April 2021

Sirtuins and their Biological Relevance in Aging and Age-Related Diseases.

Aging Dis 2020 Jul 23;11(4):927-945. Epub 2020 Jul 23.

1Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing, China.

Sirtuins, initially described as histone deacetylases and gene silencers in yeast, are now known to have many more functions and to be much more abundant in living organisms. The increasing evidence of sirtuins in the field of ageing and age-related diseases indicates that they may provide novel targets for treating diseases associated with aging and perhaps extend human lifespan. Here, we summarize some of the recent discoveries in sirtuin biology that clearly implicate the functions of sirtuins in the regulation of aging and age-related diseases. Furthermore, human sirtuins are considered promising therapeutic targets for anti-aging and ageing-related diseases and have attracted interest in scientific communities to develop small molecule activators or drugs to ameliorate a wide range of ageing disorders. In this review, we also summarize the discovery and development status of sirtuin-targeted drug and further discuss the potential medical strategies of sirtuins in delaying aging and treating age-related diseases.
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http://dx.doi.org/10.14336/AD.2019.0820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390530PMC
July 2020

Source specific PM associated with heart rate variability in the elderly with coronary heart disease: A community-based panel study.

Chemosphere 2020 Dec 20;260:127399. Epub 2020 Jun 20.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

There is increasingly concern that PM constituents play a significant role in PM-related cardiovascular outcomes. However, little is known about the associations between specific constituents of PM and risk for cardiovascular health. To evaluate the exposure to specific chemicals of PM from various sources and their cardiac effects, a longitudinal investigation was conducted with four repeated measurements of elderly participants' HRV and PM species in urban Beijing. Multiple chemicals in PM (metals, ions and PAHs) were characterized for PM source apportionment and personalized exposure assessment. Five sources were finally identified with specific chemicals as the indicators: oil combustion (1.1%, V & PAHs), secondary particle (11.3%, SO & NO), vehicle emission (1.2%, Pd), construction dust (28.7%, Mg & Ca), and coal combustion (57.7%, Se & As). As observed, each IQR increase in exposure to oil combustion (V), vehicle emission (Pd), and coal combustion (Se) significantly decreased rMSSD by 13.1% (95% CI: -25.3%, -1.0%), 27.4% (95% CI: -42.9%, -7.6%) and 24.7% (95% CI: -39.2%, -6.9%), respectively, while those of PM mass with decreases of rMSSD by 11.1% (95% CI: -19.6%, -1.9%) at lag 0. Elevated exposures to specific sources/constituents of PM disrupt cardiac autonomic function in elderly and have more adverse effects than PM mass. In the stratified analysis, medication and gender modify the associations of specific chemicals from variable sources with HRV. The findings of this study provide evidence on the roles of influential constituents of ambient air PM and their sources in terms of their adverse cardiovascular health effects.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127399DOI Listing
December 2020

HnRNP F/H associate with hTERC and telomerase holoenzyme to modulate telomerase function and promote cell proliferation.

Cell Death Differ 2020 06 20;27(6):1998-2013. Epub 2019 Dec 20.

Peking University Research Center on Aging, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University, Beijing, 100191, China.

Human telomerase RNA component hTERC comprises multiple motifs that contribute to hTERC biogenesis, holoenzyme activity, and enzyme recruitment to telomeres. hTERC contains several guanine tracts (G-tracts) at its 5'-end, but its associated proteins and potential roles in telomerase function are still poorly understood. The heterogeneous nuclear ribonucleoproteins F, H1, and H2 (hnRNP F/H) are splicing factors that preferentially bind to poly(G)-rich sequences RNA. Here, we demonstrate that hnRNP F/H associate with both hTERC and telomerase holoenzyme to regulate telomerase activity. We reveal hnRNP F/H bind to the 5'-end region of hTERC in vitro and in vivo, and identify the first three G-tracts of hTERC and qRRM1 domain of hnRNP F/H are required for their interaction. Furthermore, hnRNP F/H also directly interact with telomerase holoenzyme. Functionally, we show that hnRNP F/H plays important roles in modulating telomerase activity and telomere length. Moreover, hnRNP F/H deletion greatly impair cancer and stem cell proliferation, and induce stem cell senescence, while hnRNP F/H overexpression delay stem cell senescence. Collectively, our findings unveil a novel role of hnRNP F/H as the binding partners of hTERC and telomerase holoenzyme to regulate telomerase function.
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http://dx.doi.org/10.1038/s41418-019-0483-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244589PMC
June 2020

lncRNA functions as a ceRNA to upregulate by sponging in HCC cellular senescence.

Aging (Albany NY) 2019 09 10;11(17):7098-7122. Epub 2019 Sep 10.

Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China.

Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths and lacks effective therapies. Cellular senescence acts as a barrier against cancer progression and plays an important role in tumor suppression. Senescence associated long noncoding RNAs (SAL-RNAs) are thought to be critical regulators of cancer development. Here, the long noncoding RNA (lncRNA) myocardial infarction-associated transcript ) was first identified as an HCC specific SALncRNA. Knockdown of significantly promoted cellular senescence and inhibited HCC progression. Mechanistic study revealed that SAL- acted as a competitive endogenous RNA (ceRNA) that upregulated the expression of by sponging . Moreover, downregulation activated the tumor suppressor pathway (p53/ and /pRb) and stimulated senescent cancer cells to secrete senescence-associated secretory phenotype (SASP), which contributed to inhibition of tumor cell proliferation, and resulted in the suppression of HCC tumorigenesis. Together, our study provided mechanistic insights into a critical role of as a miRNA sponge in HCC cellular senescence, which might offer a potential therapeutic strategy for HCC treatment.
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http://dx.doi.org/10.18632/aging.102240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756895PMC
September 2019

Study on Structural Evolution, Thermochemistry and Electron Affinity of Neutral, Mono- and Di-Anionic Zirconium-Doped Silicon Clusters ZrSi ( = 6-16).

Int J Mol Sci 2019 Jun 15;20(12). Epub 2019 Jun 15.

Inner Mongolia Key Laboratory of Theoretical and Computational Chemistry Simulation, School of Chemical Engineering, Inner Mongolia University of Technology, Hohhot 010051, China.

We have carried out a global search of systematic isomers for the lowest energy of neutral and Zintl anionic Zr-doped Si clusters ZrSi ( = 6-16) by employing the ABCluster global search method combined with the mPW2PLYP double-hybrid density functional. In terms of the evaluated energies, adiabatic electron affinities, vertical detachment energies, and agreement between simulated and experimental photoelectron spectroscopy, the true global minimal structures are confirmed. The results reveal that structural evolution patterns for neutral ZrSi clusters prefer the attaching type ( = 6-9) to the half-cage motif ( = 10-13), and finally to a Zr-encapsulated configuration with a Zr atom centered in a Si cage ( = 14-16). For Zintl mono- and di-anionic ZrSi, their growth patterns adopt the attaching configuration ( = 6-11) to encapsulated shape ( = 12-16). The further analyses of stability and chemical bonding make it known that two extra electrons not only perfect the structure of ZrSi but also improve its chemical and thermodynamic stability, making it the most suitable building block for novel multi-functional nanomaterials.
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http://dx.doi.org/10.3390/ijms20122933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627843PMC
June 2019

Connection between Unusual Lattice Thermal Expansion and Cooperative Jahn-Teller Effect in Double Perovskites LaPbMSbO (M = Mn, Co, Ni).

Inorg Chem 2019 Feb 7;58(4):2888-2898. Epub 2019 Feb 7.

Chemical Engineering College , Inner Mongolia University of Technology , 49Aimin Street , Hohhot 010051 , People's Republic of China.

Lattice thermal expansion (LTE) has been investigated in double perovskites LaPbMSbO (M = Mn, Co, Ni). Ordinary LTE behavior with good thermal stability is identified for the Mn sample, whereas unusual LTE with a preferably expanded interplanar distance of (040) is revealed for Co and Ni samples. Temperature-dependent X-ray diffraction patterns ( T-XRD), Raman spectra ( T-Raman), and specific heat capacities ( T- C) consistently indicate that a rare isostructural displacive phase transition (IDPT) with a second-order phase transition nature is predominant near the critical temperature. Refinements of neutron powder diffraction (NPD) and in situ T-XRD data present temperature-sensitive bond parameters which are relevant to planar oxygen O1. X-ray photoelectron spectra (XPS) further confirm the Jahn-Teller (J-T) activated Co (HS) or Ni (HS/LS) cations at the B-site sublattice. This unusual LTE behavior could be understood by the cooperative J-T effect contributed by a Pb ion and Co/Ni ion from A- and B-site sublattices, respectively. The importance of 6s(Pb)-2p(O)-3d(Co/Ni) extended orbital hybridization on affecting thermal expansion behavior is highlighted on the basis of temperature-induced phonon mode softening. This study presents a microscopic description of connection between anisotropic thermal expansion and a cooperative J-T effect, which inspired exploration of thermal-mechanical coupled functional materials based on LaPbMSbO double perovskites.
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http://dx.doi.org/10.1021/acs.inorgchem.8b03595DOI Listing
February 2019

Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis.

Onco Targets Ther 2018 11;11:8995-9006. Epub 2018 Dec 11.

Department of Pathophysiology, Zunyi Medical University, Zunyi, Guizhou Province 563000, People's Republic of China,

Background: Resveratrol is known as a natural phytoalexin found in grapes and wine, which has significant antitumor activity under in vitro and in vivo conditions. In recent years, great progress has been made in understanding the underlying mechanisms of resveratrol in inducing cellular apoptosis of melanoma cells. Our previous study has shown that the apoptosis regulation of resveratrol in melanoma cells was independent of activation of classical apoptosis-related protein p53.

Materials And Methods: MTT assay and 5-bromo-2'-deoxyuridine staining assay were used to analyze cell viability and proliferation. Immunofluorescence analysis of γ-H2AX was employed to clarify DNA damages. Annexin V-propidine iodide/fluorescein isothiocyanate assay was performed to evaluate the cell apoptosis. The mechanisms underlying the activation of M2-type pyruvate kinase (PKM2) by Erk1/2 to stabilize and maintain Bcl-2 signaling was investigated by subcellular fractionation analyses, immunofluorescence analysis, co-immunoprecipitation assay, ubiquitination assay, and glutathione S-transferase pull-down assay.

Results: In the present study, we found that resveratrol dramatically inhibited melanoma cell proliferation and induced cell apoptosis through upregulation of p53 in a concentration-dependent manner. Conversely, p53 downregulation by short hairpin RNA couldn't rescue resveratrol-induced cell proliferation inhibition or apoptosis enlargement. Additionally, we found that resveratrol downregulated antiapoptotic protein Bcl-2 and activated Bax in the protein levels by promoting Bcl-2 degradation and cytochrome c release. Moreover, we discovered that PKM2, had a key role in cell apoptosis triggered by resveratrol through interacting with Bcl-2. Based on these results, we overexpressed PKM2 in melanoma cells and found that this prevented resveratrol-induced apoptosis by stabilizing the protein level of Bcl-2.

Conclusion: Taken together, our results provided a novel mechanism accounting for the apoptosis induction of resveratrol in melanoma cells and suggested that downregulating Erk/PKM2/Bcl-2 axis appears to be a new approach for the prevention or treatment of melanoma.
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http://dx.doi.org/10.2147/OTT.S186247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294058PMC
December 2018

RNA-binding protein RPS3 contributes to hepatocarcinogenesis by post-transcriptionally up-regulating SIRT1.

Nucleic Acids Res 2019 02;47(4):2011-2028

Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, P.R. China.

Although several studies indicate that RNA-binding proteins (RBPs) contribute to key steps in a variety of physiological processes and cancer, the detailed biological functions and mechanisms remain to be determined. By performing bioinformatics analysis using well-established hepatocellular carcinoma (HCC) datasets, we identified a set of HCC progression-associated RBPs (HPARBPs) and found that the global expression of HPARBPs was significantly correlated with patient prognosis. Among the 42 HPARBPs, human ribosomal protein S3 (RPS3) was one of the most abundant genes whose role remains uncharacterized in HCC. Gain- and loss-of-function analyses demonstrated that RPS3 promoted HCC tumorigenesis both in vitro and in vivo. Mechanistically, we revealed that silent information regulator 1 (SIRT1) was a critical target of RPS3 and was essential for sustaining the RPS3-induced malignant phenotypes of HCC cells. RPS3 stabilized SIRT1 mRNA by binding to AUUUA motifs in the 3448-3530 region of the 3' untranslated region (UTR) of SIRT1 mRNA. In addition, we found that (5-formylfuran-2-yl) methyl 4-hydroxy-2-methylenebutanoate (FMHM) inhibited HCC progression by repressing the RPS3/SIRT1 pathway. Our study unveils a novel extra-ribosomal role of RPS3 in facilitating hepatocarcinogenesis via the post-transcriptional regulation of SIRT1 expression and proposes that the RPS3/SIRT1 pathway serves as a potential therapeutic target in HCC.
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http://dx.doi.org/10.1093/nar/gky1209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393244PMC
February 2019

Molecular Characterization and Overexpression of Increases the Production of Phenolic Acids in .

Int J Mol Sci 2018 Nov 28;19(12). Epub 2018 Nov 28.

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.

Jasmonic acid (JA) carboxyl methyltransferase (JMT), a key enzyme in jasmonate-regulated plant responses, may be involved in plant defense and development by methylating JA to MeJA, thus influencing the concentrations of MeJA in plant. In this study, we isolated the gene from , an important medicinal plant widely used to treat cardiovascular disease. We present a genetic manipulation strategy to enhance the production of phenolic acids by overexpresion in . Global transcriptomic analysis using RNA sequencing showed that the expression levels of genes involved in the biosynthesis pathway of phenolic acids and MeJA were upregulated in the overexpression lines. In addition, the levels of endogenous MeJA, and the accumulation of rosmarinic acid (RA) and salvianolic acid (Sal B), as well as the concentrations of total phenolics and total flavonoids in transgenic lines, were significantly elevated compared with the untransformed control. Our results demonstrate that overexpression of promotes the production of phenolic acids through simultaneously activating genes encoding key enzymes involved in the biosynthesis pathway of phenolic acids and enhancing the endogenous MeJA levels in .
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http://dx.doi.org/10.3390/ijms19123788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321555PMC
November 2018

Semen Brassicae ameliorates hepatic fibrosis by regulating transforming growth factor-β1/Smad, nuclear factor-κB, and AKT signaling pathways in rats.

Drug Des Devel Ther 2018 11;12:1205-1213. Epub 2018 May 11.

Gannan Medical University, Ganzhou, Jiangxi, China.

Purpose: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear.

Methods: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL·kg) at a dose of 200 mg·kg twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. After Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, α-SMA, transforming growth factor (TGF)-β1, p-Smad 2/3, Smad 2/3, Smad4, NF-κB-p65, p-NF-κB-p65, IL-1β, IL-6, AKT, and p-AKT were determined using Western blotting.

Results: Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and α-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-β1, Smad4, p-Smad 2/3/Smad 2/3, p-NF-κB-p65/NF-κB-p65, IL-1β, IL-6, and p-AKT/AKT significantly decreased after the treatment.

Conclusion: These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-β1/Smad, NF-κB, and AKT signaling pathways and the reduction of extracellular matrix deposition.
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http://dx.doi.org/10.2147/DDDT.S155053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955013PMC
October 2018

The complete chloroplast genome sequence of Epipremnum aureum and its comparative analysis among eight Araceae species.

PLoS One 2018 12;13(3):e0192956. Epub 2018 Mar 12.

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Key Laboratory of Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, P.R. China.

Epipremnum aureum is an important foliage plant in the Araceae family. In this study, we have sequenced the complete chloroplast genome of E. aureum by using Illumina Hiseq sequencing platforms. This genome is a double-stranded circular DNA sequence of 164,831 bp that contains 35.8% GC. The two inverted repeats (IRa and IRb; 26,606 bp) are spaced by a small single-copy region (22,868 bp) and a large single-copy region (88,751 bp). The chloroplast genome has 131 (113 unique) functional genes, including 86 (79 unique) protein-coding genes, 37 (30 unique) tRNA genes, and eight (four unique) rRNA genes. Tandem repeats comprise the majority of the 43 long repetitive sequences. In addition, 111 simple sequence repeats are present, with mononucleotides being the most common type and di- and tetranucleotides being infrequent events. Positive selection pressure on rps12 in the E. aureum chloroplast has been demonstrated via synonymous and nonsynonymous substitution rates and selection pressure sites analyses. Ycf15 and infA are pseudogenes in this species. We constructed a Maximum Likelihood phylogenetic tree based on the complete chloroplast genomes of 38 species from 13 families. Those results strongly indicated that E. aureum is positioned as the sister of Colocasia esculenta within the Araceae family. This work may provide information for further study of the molecular phylogenetic relationships within Araceae, as well as molecular markers and breeding novel varieties by chloroplast genetic-transformation of E. aureum in particular.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192956PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846728PMC
June 2018

SIRT1 increases cardiomyocyte binucleation in the heart development.

Oncotarget 2018 Jan 3;9(8):7996-8010. Epub 2018 Jan 3.

The Lawrence D. Longo MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, USA.

SIRT1 regulates cell senescence. We investigated a novel role of SIRT1 in the regulation of cardiomyocyte terminal differentiation in the developing heart. Retinoic acid (RA)-induced binucleation of H9c2 cells was associated with increased SIRT1 expression. Inhibition of SIRT1 activity or expression significantly decreased RA-induced binucleation. SIRT1 expression was minimal in the fetal heart and significantly upregulated in the hearts of postnatal day 7 (P7) rat pups. In contrast, heart-specific miR-133a expression was high in the fetal heart but significantly reduced in P7 pup hearts. The miR-133a promoter contains a canonical HRE element and hypoxia upregulated miR-133a gene expression in the heart. SIRT1 mRNA 3'UTR has miR-133a binding sequences and miR-133a and hypoxia suppressed SIRT1 expression in cardiomyocytes. Of importance, inhibition of SIRT1 significantly reduced binucleated cardiomyocytes in the hearts of P7 pups. Taken together, the present study reveals a novel role of SIRT1 and its regulation by miR-133a in cardiomyocyte terminal differentiation of the developing heart, and suggests a potential therapeutic strategy that may impact cardiac function later in life.
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http://dx.doi.org/10.18632/oncotarget.23847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814276PMC
January 2018

Silver nanoparticles increase connexin43-mediated gap junctional intercellular communication in HaCaT cells through activation of reactive oxygen species and mitogen-activated protein kinase signal pathway.

J Appl Toxicol 2018 04 13;38(4):564-574. Epub 2017 Dec 13.

Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, Beijing, China.

Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to maintain tissue homeostasis. The aim of this study is to examine if non-coated AgNPs affect GJIC in human keratinocytes (HaCaT cells), and to identify the possible molecular mechanisms responsible for the effects. GJIC, connexin (Cx)43 protein and mRNA expression, and the effect of siRNA-mediated knockdown of Cx43 on GJIC were assessed. HaCaT cells exposed to non-coated AgNPs at different doses after a 24 hour exposure. To explore further the underlying mechanism, reactive oxygen species and mitogen-activated protein kinase pathway were evaluated after 2, 6, 12 and 24 hours. Our results revealed that non-coated AgNP exposure at subcytotoxic doses increase GJIC partially via Cx43 upregulation. Reactive oxygen species and extracellular signal-regulated kinase and activation of c-Jun N-terminal kinase were involved in the AgNP-induced upregulation of Cx43. This study provides new insight into the potential mechanism of AgNP biological activity.
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http://dx.doi.org/10.1002/jat.3563DOI Listing
April 2018

The relationship between the autonomic nervous function and early renal dysfunction in elderly patients with mild-to-moderate essential hypertension.

Clin Exp Hypertens 2018 8;40(2):136-140. Epub 2017 Aug 8.

b Clinical laboratory , Civil Aviation General Hospital , Beijing , PR China.

Objective: This study investigated the relationship between autonomic nervous function and early renal dysfunction in elderly patients with mild-to-moderate essential hypertension (EH).

Design: A total of 223 elderly patients with mild-to-moderate EH were enrolled. Urinary albumin excretion (UAE) and urinary creatinine (UCr) were measured in all elderly patients with mild-to-moderate EH, and urinary albumin to creatinine ratio (ACR) was calculated (ACR = UAE/UCr × 0.113). All patients were divided into two groups such as ACR normal group (109 cases) and abnormal ACR group (114 cases) according to the results of ACR. Synchronic 24-hour ambulatory blood pressure monitoring and 24-hour ambulatory electrocardiogram were detected for all patients to simultaneously monitor heart rate variability (HRV) and blood pressure variability (BPV).

Results: The level of 24-hour SSD, dSSD, and nSSD and 24-hour PP (parameters of BPV) increased significantly (P < 0.028, P < 0.023, P < 0.027 and P < 0.019, respectively), while the level of RMSSD, pNN50, SDNN, and SDANN (parameters of HRV) decreased significantly(P < 0.048, P < 0.029, P < 0.025 and P < 0.022, respectively) in abnormal ACR group than in normal ACR group. Multiple logistic regression analysis showed that ACR was closely correlated with 24-hour SSD, 24-hour PP, SDANN, and SDNN (ß = 1.261, P = 0.000; ß = 1.121, P = 0.003; ß = -1.741, P = 0.000 and ß = -1.231, P = 0.002, respectively).

Conclusions: HRV (SDANN, SDNN) and BPV (24-hour SSD, dSSD, nSSD) were significantly correlated to ACR in patients with mild-to-moderate EH. This result suggested that sympathetic activation was closely related with early renal dysfunction in elderly patients with mild-to-moderate EH.
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http://dx.doi.org/10.1080/10641963.2017.1346110DOI Listing
June 2018

Pregnancy Reprograms Large-Conductance Ca-Activated K Channel in Uterine Arteries: Roles of Ten-Eleven Translocation Methylcytosine Dioxygenase 1-Mediated Active Demethylation.

Hypertension 2017 06 10;69(6):1181-1191. Epub 2017 Apr 10.

Institute for Fetology, First Hospital of Soochow University, Suzhou, China (X.-Q.H., Z.X., L.Z.); Lawrence D. Longo MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, CA (X.-Q.H., C.D., D.X., X.H., Z.X., L.Z.); Department of Chemistry and Biochemistry, California State University, San Bernardino (S.Y.).

The large-conductance Ca-activated K (BK) channel is of critical importance in pregnancy-mediated increase in uterine artery vasodilation and blood flow. The present study tested the hypothesis that active DNA demethylation plays a key role in pregnancy-induced reprogramming and upregulation of BK channel β1 subunit (BKβ1) in uterine arteries. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Pregnancy significantly increased the expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in uterine arteries. A half-palindromic estrogen response element was identified at the TET1 promoter, and estrogen treatment increased TET1 promoter activity and TET1 expression in uterine arteries. In accordance, pregnancy and steroid hormone treatment resulted in demethylation of BKβ1 promoter by increasing 5-hydroxymethylcytosine and decreasing 5-methylcytosine at the CpG in the Sp1 binding site that is of critical importance in the regulation of the promoter activity and BKβ1 expression. Inhibition of TET1 with fumarate significantly decreased BKβ1 expression in uterine arteries of pregnant animals and blocked steroid hormone-induced upregulation of BKβ1. Functionally, fumarate treatment inhibited pregnancy and steroid hormone-induced increases in BK channel current density and BK channel-mediated relaxations. In addition, fumarate blocked pregnancy and steroid hormone-induced decrease in pressure-dependent myogenic tone of the uterine artery. The results demonstrate a novel mechanism of estrogen-mediated active DNA demethylation in reprogramming of BK channel expression and function in the adaption of uterine circulation during pregnancy.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426984PMC
June 2017

SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation.

Aging (Albany NY) 2016 09;8(10):2308-2323

Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing, 100191, China.

Sirtuin6(SIRT6) has been implicated as a key factor in aging and aging-related diseases. However, the role of SIRT6 in cellular senescence has not been fully understood. Here, we show that SIRT6 repressed the expression of p27 (p27) in cellular senescence. The expression of SIRT6 was reduced during cellular senescence, whereas enforced SIRT6 expression promoted cell proliferation and antagonized cellular senescence. In addition, we demonstrated that SIRT6 promoted p27 degradation by proteasome and SIRT6 decreased the acetylation level and protein half-life of p27. p27 acetylation increased its protein stability. Furthermore, SIRT6 directly interacted with p27. Importantly, p27 was strongly acetylated and had a prolonged protein half-life with the reduction of SIRT6 when cells were senescent, compared with those young cells. Finally, SIRT6 markedly rescued senescence induced by p27. Our findings indicate that SIRT6 decreases p27 acetylation, leading to its degradation via ubiquitin-proteasome pathway and then delays cellular senescence.
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http://dx.doi.org/10.18632/aging.101038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115890PMC
September 2016

hnRNP A1 antagonizes cellular senescence and senescence-associated secretory phenotype via regulation of SIRT1 mRNA stability.

Aging Cell 2016 Dec 9;15(6):1063-1073. Epub 2016 Sep 9.

Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.

Senescent cells display a senescence-associated secretory phenotype (SASP) which contributes to tumor suppression, aging, and cancer. However, the underlying mechanisms for SASP regulation are not fully elucidated. SIRT1, a nicotinamide adenosine dinucleotide-dependent deacetylase, plays multiple roles in metabolism, inflammatory response, and longevity, etc. However, its posttranscriptional regulation and its roles in cellular senescence and SASP regulation are still elusive. Here, we identify the RNA-binding protein hnRNP A1 as a posttranscriptional regulator of SIRT1, as well as cell senescence and SASP regulator. hnRNP A1 directly interacts with the 3' untranslated region of SIRT1 mRNA, promotes its stability, and increases SIRT1 expression. hnRNP A1 delays replicative cellular senescence and prevents from Ras OIS via upregulation of SIRT1 expression to deacetylate NF-κB, thus blunting its transcriptional activity and subsequent IL-6/IL-8 induction. hnRNP A1 overexpression promotes cell transformation and tumorigenesis in a SIRT1-dependent manner. Together, our findings unveil a novel posttranscriptional regulation of SIRT1 by hnRNP A1 and uncover a critical role of hnRNP A1-SIRT1-NF-κB pathway in regulating cellular senescence and SASP expression.
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http://dx.doi.org/10.1111/acel.12511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398525PMC
December 2016

The association between oxidative stress, activator protein-1, inflammatory, total antioxidant status and artery stiffness and the efficacy of olmesartan in elderly patients with mild-to-moderate essential hypertension.

Clin Exp Hypertens 2016;38(4):365-9. Epub 2016 May 9.

c Department of Cardiology , Xiangya Second Hospital of Central South University , Changsha , PR China.

This study investigated the change of oxidative stress, activator protein-1 (AP-1), inflammatory, total antioxidant status (TAS) and artery stiffness, and explored the relationship between these characteristics and the efficacy of olmesartan intervention in elderly patients with mild-to-moderate essential hypertension (EH). In total, 386 elderly patients with EH and 353 normotensive controls were recruited. All study subjects had oxidative stress markers, AP-1, inflammatory factors, TAS and brancial-ankle artery pulse wave velocity (ba-PWV) measured. In total, 193 elderly patients with EH were randomized to olmesartan and were matched with 193 normotensive controls to observe the change of index above mentioned before and after the treatment. Compared with the controls, superoxide dismutase (SOD) and TAS were significantly reduced in patients with EH, and malondialdehyde (MDA), AP-1, high-sensitivity C-reactive protein (Hs-CRP), Monocyte Chemoattractant Protein-1 (MCP-1), heart rate, endothelin-1 (ET-1), TAS and ba-PWV were significantly increased (P < 0.01 for all). Pearson's correlation analysis showed that SOD and TAS were negatively related to AP-1 (P < 0.05 for all), and that blood pressure (BP), age, MDA, Hs-CRP, MCP-1, ET-1 were positively related to AP-1 (P < 0.01 for all). Multivariate linear regression analysis showed that BP, SOD, MDA, AP-1, Hs-CRP, MCP-1, ET-1, TAS, heart rate and age were independent risk factors for ba-PWV. After treatment with olmesartan, SOD and TAS were increased, while BP, heart rate, AP-1 and inflammatory factors were reduced with significant improvement in ba-PWV (P < 0.05 for all). More increase of arterial stiffness was reported in elderly hypertensive patients with greater oxidative stress, inflammatory, AP-1, heart rate, and lower TAS. Higher oxidative stress, AP-1 and inflammatory may predict higher arterial stiffness. Olmesartan may increase TAS, yet inhibit oxidative stress, AP-1, inflammatory, and heart rate with improved artery stiffness in elderly hypertensive patients.
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http://dx.doi.org/10.3109/10641963.2015.1131285DOI Listing
December 2016

HDAC4 stabilizes SIRT1 via sumoylation SIRT1 to delay cellular senescence.

Clin Exp Pharmacol Physiol 2016 Jan;43(1):41-6

Department of Biochemistry & Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China.

The nicotinamide adenine dinucleotide-dependent protein deacetylase silent information regulator 2 (Sir2) regulates cellular lifespan in several organisms. Histone deacetylase 4 (HDAC4) belongs to the class IIa group of HDACs; this class of HDACs is composed of proteins that are important regulators of gene expression that control pleiotropic cellular functions. However, the role of HDAC4 in cellular senescence is still unknown. This study shows that the expression patterns of HDAC4 and Sirtuin 1 (SIRT1; the mammalian homolog of Sir2) are positively correlated during cellular senescence. Moreover, the overexpression of HDAC4 delays senescence, whereas the knockdown of HDAC4 leads to premature senescence in human fibroblasts. Furthermore, it is demonstrated that HDAC4 increases endogenous SIRT1 expression by enhancing its sumoylation modification levels, thereby stabilizing its protein levels. This study, therefore, provides a new molecular mechanism for the regulation of cellular senescence.
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http://dx.doi.org/10.1111/1440-1681.12496DOI Listing
January 2016

The complete chloroplast genome sequence of Alocasia macrorrhizos.

Authors:
Bin Wang Limin Han

Mitochondrial DNA A DNA Mapp Seq Anal 2016 09 10;27(5):3464-5. Epub 2015 Aug 10.

a National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Science, Shaanxi Normal University , Xi'an , PR China .

The complete chloroplast sequence of Alocasia macrorrhizos is 154 995 bp in length, containing a pair of inverted repeats of 25 944 bp separated by a large single-copy (LSC) region and a small single-copy (SSC) region of 87 366 bp and 15 741 bp, respectively. The chloroplast genome encodes 132 predicted functional genes, including 87 protein-coding genes, four ribosomal RNA genes, and 37 transfer RNA genes, 18 of which are duplicated in the inverted repeat regions. In these genes, 16 genes contained single intron and two genes comprising double introns. A maximum-likelihood phylogenetic analysis using complete chloroplast genome revealed that A. macrorrhizos does not belong to Araceae family, which infers that the A. macrorrhizos is distant from the species in Araceae family.
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http://dx.doi.org/10.3109/19401736.2015.1066350DOI Listing
September 2016

The complete chloroplast genome sequence of medicinal plant Pinellia ternata.

Mitochondrial DNA A DNA Mapp Seq Anal 2016 07 8;27(4):2921-2. Epub 2015 Jul 8.

a National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China , College of Life Science, Shaanxi Normal University , Xi'an , PR China .

Pinellia ternata is an important medicinal plant used in the treatment of cough, to dispel phlegm, to calm vomiting and to terminate early pregnancy, as an anti-ulcer and anti-tumor medicine. In this study, we found that the complete chloroplast genome of Pinellia ternata was 164 013 bp in length, containing a pair of inverted repeats of 25 625 bp separated by a large single-copy region and a small single-copy region of 89 783 bp and 22 980 bp, respectively. The chloroplast genome encodes 132 predicted functional genes, including 87 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The chloroplast DNA is GC-rich (36.7%). The phylogenetic analysis showed a strong sister relationship with Colocasia esculenta, which also strongly supports the position of Pinellia ternata. The complete chloroplast genome sequence of Pinellia ternata reported here has the potential to advance population and phylogenetic studies of this medicinal plant.
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http://dx.doi.org/10.3109/19401736.2015.1060441DOI Listing
July 2016

The complete chloroplast genome sequence of Dieffenbachia seguine (Araceae).

Mitochondrial DNA A DNA Mapp Seq Anal 2016 07 8;27(4):2913-4. Epub 2015 Jul 8.

a Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry , National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University , Xi'an , PR China .

The nucleotide sequence of the chloroplast genome from Dieffenbachia seguine is the first to have complete genome sequence from genus of Dieffenbachia family Araceae. The genome size is 163 699 bp in length, with 36.4% GC content. A pair of inverted repeats (IRs, 25 235 bp) is separated by a large single copy region (LSC, 90 780 bp) and a small single copy region (SSC, 22 449 bp). The chloroplast genome contains 113 unique genes, 88 protein-coding genes, 37 tRNA genes, and four rRNA genes. In these genes, 16 genes contained single intron and two genes composed of double introns. A maximum likelihood phylogenetic analysis using complete chloroplast genome revealed that Dieffenbachia seguine belongs to the Araceae family of the Arecidae group, which is conform to the traditional classification.
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http://dx.doi.org/10.3109/19401736.2015.1060436DOI Listing
July 2016

The complete chloroplast genome sequence of Spathiphyllum kochii.

Mitochondrial DNA A DNA Mapp Seq Anal 2016 07 2;27(4):2973-4. Epub 2015 Jul 2.

a National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Science, Shaanxi Normal University , Xi'an , PR China .

The complete chloroplast sequence of the Spathiphyllum kochii is 163 368 bp in length, containing a pair of inverted repeats of 25 270 bp separated by a large single-copy region and a small single-copy region of 90 482 bp and 22 346 bp, respectively. The chloroplast genome encodes 133 predicted functional genes, including 88 protein-coding genes, four ribosomal RNA genes and 37 transfer RNA genes, 18 of which are duplicated in the inverted repeat regions. The cpDNA is GC-rich (37.6%). The chloroplast genome of S. kochii reported here will lay basis for identification, utilization and protection of its germplasm resources.
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http://dx.doi.org/10.3109/19401736.2015.1060466DOI Listing
July 2016

CO2 Fixation into Novel CO2 Storage Materials Composed of 1,2-Ethanediamine and Ethylene Glycol Derivatives.

Chemphyschem 2015 Jul 7;16(10):2106-9. Epub 2015 May 7.

College of Chemical Engineering, Inner Mongolia University of Technology, Huhhot 010051 (China).

A new CO2 fixation process into solid CO2 -storage materials (CO2 SMs) under mild conditions has been developed. The novel application of amine-glycol systems to the capture, storage, and utilization of CO2 with readily available 1,2-ethanediamine (EDA) and ethylene glycol derivatives (EGs) was demonstrated. Typically, the CO2 SMs were isolated in 28.9-47.5 % yields, followed by extensive characterization using (13) C NMR, XRD, and FTIR. We found that especially the resulting poly-ethylene-glycol-300-based CO2 SM (PCO2 SM) product could be processed into stable tablets for CO2 storage; the aqueous PCO2 SM solution exhibited remarkable CO2 capturing and releasing capabilities after multiple cycles. Most importantly, the EDA and PEG 300 released from PCO2 SM were found to act as facilitative surfactants for the multiple preparation of CaCO3 microparticles with nano-layer structure.
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http://dx.doi.org/10.1002/cphc.201500206DOI Listing
July 2015

Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation.

Proc Natl Acad Sci U S A 2014 May 14;111(21):7683-8. Epub 2014 May 14.

Peking University Research Center on Aging,Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China;

Oncogene-induced senescence (OIS) is an initial barrier to tumor development. Reactive oxygen species (ROS) is critical for oncogenic Ras OIS, but the downstream effectors to mediate ROS signaling are still relatively elusive. Senescent cells develop a senescence-associated secretory phenotype (SASP). However, the mechanisms underlying the regulation of the SASP are largely unknown. Here, we identify protein kinase D1 (PKD1) as a downstream effector of ROS signaling to mediate Ras OIS and SASP. PKD1 is activated by oncogenic Ras expression and PKD1 promotes Ras OIS by mediating inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) via modulation of NF-κB activity. We demonstrate that ROS-protein kinase Cδ (PKCδ)-PKD1 axis is essential for the establishment and maintenance of IL-6/IL8 induction. In addition, ablation of PKD1 causes the bypass of Ras OIS, and promotes cell transformation and tumorigenesis. Together, these findings uncover a previously unidentified role of ROS-PKCδ-PKD1 pathway in Ras OIS and SASP regulation.
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http://dx.doi.org/10.1073/pnas.1310972111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040603PMC
May 2014
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