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1.
Environ Geochem Health ; 44(9): 2919-2942, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34762254

ABSTRACT

Rampant corruption exists in China's energy-intensive industries. However, we know little about the nexus of corruption and enterprise green innovation in China's energy-intensive industries. This paper discusses the impact of anti-corruption on enterprises' green innovation and its effect margin. Analyzing the panel data of Chinese listed enterprises in energy-intensive industries from 2009 to 2017, we find that anti-corruption played a positive role in stimulating enterprises' green innovation investments in energy-intensive industries. Then we adopt the instrumental variable approach and difference-in-differences model to alleviate the endogeneity problem. Moreover, we find that research and development investments from state-owned, high-tech enterprises and enterprises in the regions with more government intervention or weaker intellectual property protection were more prominent after the anti-corruption campaign. Finally, political connection played an intermediary role in this process, in which only the government-official political connection worked. Our results highlight the roles of enterprises' attributes and environmental characteristics as important factors in the relationship between anti-corruption and green innovation investments. Policymakers should enhance the control of corruption to boost green innovation in energy-intensive industries.


Subject(s)
Industry , China
2.
Proc Natl Acad Sci U S A ; 117(27): 15642-15649, 2020 07 07.
Article in English | MEDLINE | ID: mdl-32571927

ABSTRACT

The RNA polymerase (RNAP) trigger loop (TL) is a mobile structural element of the RNAP active center that, based on crystal structures, has been proposed to cycle between an "unfolded"/"open" state that allows an NTP substrate to enter the active center and a "folded"/"closed" state that holds the NTP substrate in the active center. Here, by quantifying single-molecule fluorescence resonance energy transfer between a first fluorescent probe in the TL and a second fluorescent probe elsewhere in RNAP or in DNA, we detect and characterize TL closing and opening in solution. We show that the TL closes and opens on the millisecond timescale; we show that TL closing and opening provides a checkpoint for NTP complementarity, NTP ribo/deoxyribo identity, and NTP tri/di/monophosphate identity, and serves as a target for inhibitors; and we show that one cycle of TL closing and opening typically occurs in each nucleotide addition cycle in transcription elongation.


Subject(s)
DNA-Directed RNA Polymerases/chemistry , DNA/chemistry , RNA/chemistry , Transcription, Genetic , Catalytic Domain , DNA/genetics , DNA-Directed RNA Polymerases/genetics , DNA-Directed RNA Polymerases/ultrastructure , Escherichia coli/genetics , Fluorescence Resonance Energy Transfer , Models, Molecular , Nucleotides , Protein Conformation , Protein Folding , RNA/genetics , Single Molecule Imaging
3.
Int J Antimicrob Agents ; 48(3): 317-20, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27449540

ABSTRACT

Scrub typhus, caused by Orientia tsutsugamushi, has recently emerged in northern China where the disease had not been known to exist. Although doxycycline and azithromycin are the recommended agents for the treatment of scrub typhus, clinical responses depend both on the susceptibilities of various O. tsutsugamushi strains and the severity of the disease. A retrospective analysis was conducted on patients diagnosed with mild scrub typhus from August 2013 to January 2016 in the Affiliated Hospital of Nantong University, northern China. A total of 40 patients who received minocycline treatment and 34 patients who received azithromycin treatment were included in the analysis. All patients except one defervesced within 120 h after initiating antimicrobial therapy. Kaplan-Meier curves in association with log-rank test showed that the median time to defervescence was significantly shorter for the minocycline-treated group than the azithromycin-treated group (P = 0.003). There were no serious adverse events during treatment. No relapse occurred in either group during the 1-month follow-up period. In conclusion, both minocycline and azithromycin are effective and safe for the treatment of mild scrub typhus, but minocycline is more active than azithromycin against O. tsutsugamushi infection acquired in northern China.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Minocycline/therapeutic use , Scrub Typhus/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , China , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Male , Middle Aged , Minocycline/adverse effects , Pregnancy , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
4.
Methods Mol Biol ; 1276: 101-31, 2015.
Article in English | MEDLINE | ID: mdl-25665560

ABSTRACT

A three-step procedure comprising (1) unnatural-amino-acid mutagenesis with 4-azido-phenylalanine, (2) Staudinger-Bertozzi ligation with a probe-phosphine derivative, and (3) in vitro reconstitution of RNA polymerase (RNAP) enables the efficient site-specific incorporation of a fluorescent probe, a spin label, a cross-linking agent, a cleaving agent, an affinity tag, or any other biochemical or biophysical probe, at any site of interest in RNAP. Straightforward extensions of the procedure enable the efficient site-specific incorporation of two or more different probes in two or more different subunits of RNAP. We present protocols for synthesis of probe-phosphine derivatives, preparation of RNAP subunits and the transcription initiation factor σ, unnatural amino acid mutagenesis of RNAP subunits and σ, Staudinger ligation with unnatural-amino-acid-containing RNAP subunits and σ, quantitation of labelling efficiency and labelling specificity, and reconstitution of RNAP.


Subject(s)
Amino Acids/metabolism , DNA-Directed RNA Polymerases/chemistry , DNA-Directed RNA Polymerases/metabolism , Fluorescent Dyes/metabolism , Molecular Biology/methods , Amino Acids/genetics , Azides , DNA-Directed RNA Polymerases/genetics , Escherichia coli , Mutagenesis/genetics , Phenylalanine/analogs & derivatives , Phosphines , Plasmids/genetics , Sigma Factor/genetics
5.
Apoptosis ; 16(3): 288-300, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21107699

ABSTRACT

Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood. In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH3)2Cl]2L¹}(NO3)2 (1) and {[cis-Pt(NH3)2Cl]2L²}(NO3)2 (2) (L¹ = α,α'-diamino-p-xylene, L² = 4,4'-methylenedianiline) has been studied using cisplatin as a reference. The effect of platinum complexes on the proliferation, death mode, mitochondrial membrane potential, and cell cycle progression has been examined by MTT assay and flow cytometry. The activation of cell cycle checkpoint kinases (CHK1/2), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) of the cells by the complexes has also been analyzed using phospho-specific flow cytometry. Complex 1 is more cytotoxic than complex 2 and cisplatin at most concentrations; complex 2 and cisplatin are comparably cytotoxic. These complexes kill the cells through an apoptotic or apoptosis-like pathway characterized by exposure of phosphatidylserine and dissipation of mitochondrial membrane potential. Complex 1 shows the strongest inductive effect on the morphological changes of the cells, followed by cisplatin and complex 2. Complexes 1 and 2 arrest the cell cycle in G2 or M phase, while cisplatin arrests the cell cycle in S phase. The influence of these complexes on CHK1/2, ERK1/2, and p38 MAPK varies with the dose of the drugs or reaction time. Activation of phospho-ERK1/2 and phospho-p38 MAPK by these complexes is closely related to the cytostatic activity. The results demonstrate that dinuclear platinum(II) complexes can induce some cellular responses different from those caused by cisplatin.


Subject(s)
Cisplatin/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Platinum/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Cycle/drug effects , Cell Death/drug effects , Cell Line, Tumor , Cell Shape/drug effects , Cell Size/drug effects , Checkpoint Kinase 1 , Checkpoint Kinase 2 , Cisplatin/chemistry , Cisplatin/pharmacology , Drug Screening Assays, Antitumor , Female , Flow Cytometry , Humans , Membrane Potential, Mitochondrial/drug effects , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Ovarian Neoplasms/enzymology , Phosphorylation/drug effects , Platinum/chemistry , Platinum/pharmacology , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
6.
Chemistry ; 16(47): 14181-9, 2010 Dec 17.
Article in English | MEDLINE | ID: mdl-20967899

ABSTRACT

DNA condensing agents play a critical role in gene therapy. A tetranuclear nickel(II) complex, [Ni(II)(4)(L-2H)(H(2)O)(6)(CH(3)CH(2)OH)(2)]·6NO(3) (L=3,3',5,5'-tetrakis{[(2-hydroxyethyl)(pyridin-2-ylmethyl)amino]methyl}biphenyl-4,4'-diol), has been synthesized as a nonviral vector to induce DNA condensation. X-ray crystallographic data indicate that the complex crystallizes in the monoclinic system with space group P2(1)/n, a=10.291(9), b=24.15(2), c=13.896(11) Å, and ß=98.175(13)°. The DNA condensation induced by the complex has been investigated by means of UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, dynamic light scattering, atomic force microscopy, gel electrophoresis assay, and zeta potential analysis. The complex interacts strongly with DNA through electrostatic attraction and induces its condensation into globular nanoparticles at low concentration. The release of DNA from its compact state has been achieved using the chelator ethylenediaminetetraacetic acid (EDTA) for the first time. Other essential properties, such as DNA cleavage inactivity and biocompatibility, have also been examined in vitro. In general, the complex satisfies the requirements of a gene vector in all of these respects.


Subject(s)
DNA/chemistry , Genetic Vectors/chemistry , Nickel/chemistry , Organometallic Compounds/chemistry , Animals , Crystallography, X-Ray , DNA Cleavage , Electrochemistry , Ligands , Molecular Structure , Spectrophotometry, Ultraviolet
7.
Chem Commun (Camb) ; 46(8): 1212-4, 2010 Feb 28.
Article in English | MEDLINE | ID: mdl-20449253

ABSTRACT

Platinum(II) complexes bearing geminal bisphosphonate moieties have excellent solubility in both organic and aqueous solutions and show considerable cytotoxicity against human osteosarcoma (MG-63) and ovarian cancer (COC1) cell lines with different apoptotic pathways from that of cisplatin.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Osteosarcoma/drug therapy , Ovarian Neoplasms/drug therapy , Platinum Compounds/chemistry , Platinum Compounds/pharmacology , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Line, Tumor , Cisplatin/pharmacology , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Female , Humans , Models, Molecular , Platinum Compounds/chemical synthesis
8.
Biochem Pharmacol ; 80(3): 344-51, 2010 Aug 01.
Article in English | MEDLINE | ID: mdl-20399754

ABSTRACT

The primary objective was to understand more deeply the molecular mechanism underlying different antitumor effects of dinuclear Pt(II) complexes containing aromatic linkers of different length, {[cis-Pt(NH(3))(2)Cl](2)(4,4'-methylenedianiline)}(2+) (1) and {[cis-Pt(NH(3))(2)Cl](2)(alpha,alpha'-diamino-p-xylene)}(2+) (2). These complexes belong to a new generation of promising polynuclear platinum drugs resistant to decomposition by sulfur nucleophiles which hampers clinical use of bifunctional polynuclear trans Pt(II) complexes hitherto tested. Results obtained with the aid of methods of molecular biophysics and pharmacology reveal differences and new details of DNA modifications by 1 and 2 and recognition of these modifications by cellular components. The results indicate that the unique properties of DNA interstrand cross-links of this class of polynuclear platinum complexes and recognition of these cross-links may play a prevalent role in antitumor effects of these metallodrugs. Moreover, the results show for the first time a strong specific recognition and binding of high-mobility-group-domain proteins, which are known to modulate antitumor effects of clinically used platinum drugs, to DNA modified by a polynuclear platinum complex.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cisplatin/chemistry , Cisplatin/pharmacology , Cross-Linking Reagents/chemistry , Cross-Linking Reagents/pharmacology , Antineoplastic Agents/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Cisplatin/metabolism , Cross-Linking Reagents/metabolism , DNA Adducts/chemistry , DNA Adducts/metabolism , DNA Damage/drug effects , DNA Damage/physiology , HeLa Cells , Humans
9.
Inorg Chem ; 49(5): 2541-9, 2010 Mar 01.
Article in English | MEDLINE | ID: mdl-20121144

ABSTRACT

Copper-based artificial metallonucleases are likely to satisfy more biomedical requirements if their DNA cleavage efficiency and selectivity could be further improved. In this study, two copper(II) complexes, [CuL(1)Cl(2)] (1) and [CuL(2)Cl(2)] (2), and two copper(II)-platinum(II) heteronuclear complexes, [CuPtL(1)(DMSO)Cl(4)] (3) and [CuPtL(2)(DMSO)Cl(4)] (4), were synthesized using two bifunctional ligands, N-[4-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L(1)) and N-[3-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L(2)). These complexes have been characterized by elemental analysis, electrospray ionization mass spectrometry, IR spectroscopy, and UV-vis spectroscopy. The DNA binding ability of these complexes follows an order of 1 < 2 < 3 < 4, as revealed by the results of spectroscopy and agarose gel electrophoresis studies. Their cleavage activity toward supercoiled pUC19 plasmid DNA is prominent at micromolar concentration levels in the presence of ascorbic acid. The introduction of a platinum(II) center to the copper(II) complexes induces a significant enhancement in cleavage activity as compared with copper(II) complexes alone. These results show that the presence of a platinum(II) center in copper(II) complexes strengthens both their DNA binding ability and DNA cleavage efficiency.


Subject(s)
Biomimetic Materials/chemistry , Biomimetic Materials/metabolism , Copper/chemistry , DNA/metabolism , Deoxyribonucleases/chemistry , Deoxyribonucleases/metabolism , Platinum/chemistry , Animals , Cattle , Drug Design , Isomerism , Kinetics , Ligands , Methylamines/chemistry , Pyridines/chemistry , Reactive Oxygen Species/metabolism , Spectrum Analysis
10.
Dalton Trans ; (48): 10889-95, 2009 Dec 28.
Article in English | MEDLINE | ID: mdl-20023919

ABSTRACT

The DNA binding ability and binding mode of platinum complexes are crucial factors that govern their cytotoxic activity. In this work, circular dichroism spectroscopy, gel electrophoresis and MALDI-TOF MS spectrometry combined with enzymatic degradation have been used to elucidate the role of bridging ligands in DNA-binding ability and cross-linking patterns of two dinuclear antitumour active platinum(II) complexes, {[cis-Pt(NH(3))(2)Cl](2)L1}(NO(3))(2) (1, L1= 4,4'-methylenedianiline) and {[cis-Pt(NH(3))(2)Cl](2)L2}(NO(3))(2) (2, L2 = alpha,alpha'-diamino-p-xylene). Although both complexes have two cis-diammine-Pt(II) moieties (1,1/c,c), complex 1 exhibits much higher DNA-binding ability than complex 2. The former readily forms both 1,3- and 1,4-intrastrand cross-links with DNA oligonucleotides, while the latter preferentially forms 1,4- rather than 1,3-intrastrand cross-links. Cytotoxicity studies against a human non-small-cell lung cancer cell line (A549) demonstrate that complex 1 has higher activity than 2. These results show that the linker properties play a critical role in controlling the DNA-binding and cross-linking abilities and in modulating the cytotoxicity of dinuclear platinum complexes.


Subject(s)
Antineoplastic Agents/chemistry , Cross-Linking Reagents/chemistry , DNA/metabolism , Ligands , Organoplatinum Compounds/chemistry , Platinum/chemistry , Antineoplastic Agents/toxicity , Base Sequence , Cell Line, Tumor , Circular Dichroism , DNA/chemistry , Humans , Kinetics , Organoplatinum Compounds/toxicity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
11.
J Biochem Mol Toxicol ; 23(4): 295-302, 2009.
Article in English | MEDLINE | ID: mdl-19705364

ABSTRACT

Two copper(II) terpyridine complexes, [Cu(atpy)(NO(3))(H(2)O)](NO(3)) 3H(2)O (1) and [Cu(ttpy)(NO(3))(2)] (2) (atpy = 4'-p-N9-adeninylmethyl-phenyl-2,2':6,2''-terpyridine; ttpy = 4'-p-tolyl-2,2':6,2''-terpyridine) exhibited high cytotoxicity, with average ten times more potency than cisplatin against the human cervix carcinoma cell line (HeLa), the human liver carcinoma cell line (HepG2), the human galactophore carcinoma cell line (MCF7), and the human prostate carcinoma cell line (PC-3). The cytotoxicity of the complex 1 was lower than that of the complex 2. Both complexes showed more efficient oxidative DNA cleavage activity under irradiation with UV light at 260 nm than in the presence of ascorbic acid. Especially, complex 1 exhibited evident photoinduced double-stranded DNA cleavage activity. The preliminary mechanism experiments revealed that hydrogen peroxide was involved in the oxidative DNA damage induced by both complexes. From the absorption titration data, the DNA-binding affinity of the complexes with surpersoiled plasmid pUC19 DNA, polydAdT, and polydGdC was calculated and complex 2 showed higher binding affinity than complex 1 with all these substrates. The DNA cleavage ability and DNA-binding affinity of both complexes depended on the substituent group on the terpyrdine ligands.


Subject(s)
Copper/toxicity , DNA/metabolism , Deoxyribonucleases/metabolism , Pyridines/toxicity , Cell Death/drug effects , Cell Death/radiation effects , Cell Line, Tumor , Electrophoresis, Agar Gel , Humans , Inhibitory Concentration 50 , Plasmids/genetics , Spectrophotometry, Ultraviolet , Ultraviolet Rays
12.
Chemistry ; 15(21): 5245-53, 2009.
Article in English | MEDLINE | ID: mdl-19350599

ABSTRACT

The DNA binding and cross-linking modes of a trinuclear platinum complex [Pt(3)Cl(3)(hptab)][ClO(4)](3) (1; hptab = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene) and its dinuclear analogue [Pt(2)Cl(2)(m-tpxa)]Cl(2) (2; m-tpxa = N,N,N',N'-tetra(2-pyridylmethyl)-m-xylylene diamine) are reported and compared. The adducts of 1 and 2 with 18-mer duplex N1, 5'-d(GAAGAAGTCACAAAATGT)-3'5'-d(ACATTTTGTGACTTCTTC)-3', have been characterized by means of denaturing polyacrylamide gels, Maxam-Gilbert sequencing, and MALDI-TOF mass spectrometry combined with enzymatic degradation to obtain insights into structural features responsible for the differences in their antitumor activities. The cytotoxic-active complex 1 readily forms various DNA adducts, such as through 1,3- and 1,4-intrastrand cross-links, and in particular, the unique and unprecedented interstrand cross-linked triadducts. In contrast, the cytotoxic-inactive complex 2 preferentially forms 1,4-intrastrand rather than 1,3-intra- and -interstrand cross-links. Digestion of the DNA adducts of 1 shows that the cleavage is completely blocked at one nucleotide before the cross-linked guanine residues on the opposite strand, a feature that appears to be unprecedented in antitumor platinum complexes. In the case of 2, the cleavage bypasses the first platinated guanine site and stops at one nucleotide prior to the second platinated site, confirming that very few 1,3-intrastrand cross-links are formed by 2. These results are supported by molecular-modeling studies of intra- and interstrand cross-links of duplex N1 with 1 and 2. The remarkable differences between 1 and 2 in DNA binding and cross-linking provide mechanistic insights into their different cytotoxicity against the tumor cell lines; these insights are useful for designing future antitumor agents.


Subject(s)
Antineoplastic Agents/pharmacology , Cross-Linking Reagents/pharmacology , DNA, Neoplasm/chemistry , Organoplatinum Compounds/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Base Sequence , Cell Line, Tumor , Cross-Linking Reagents/chemistry , Cross-Linking Reagents/metabolism , DNA, Neoplasm/genetics , Guanine/chemistry , Humans , Models, Molecular , Molecular Sequence Data , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Nucleic Acid Conformation , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/metabolism , Spectrometry, Fluorescence
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