Publications by authors named "Qiuyue Zhang"

40 Publications

Targeting the HSP90-CDC37-kinase chaperone cycle: A promising therapeutic strategy for cancer.

Med Res Rev 2021 Apr 12. Epub 2021 Apr 12.

State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, China.

Heat shock protein 90 (HSP90) is an indispensable molecular chaperone that facilitates the maturation of numerous oncoproteins in cancer cells, including protein kinases, ribonucleoproteins, steroid hormone receptors, and transcription factors. Although over 30 HSP90 inhibitors have steadily entered clinical trials, further clinical advancement has been restricted by their limited efficacy, inevitable heat shock response, and multiple side-effects, likely induced via an ATP inhibition mechanism. Since both ATP and various co-chaperones play essential roles in the HSP90 chaperone cycle to achieve integrated function, optimal therapeutics require an understanding of the dynamic interactions among HSP90, ATP, and cochaperones. To date, continuous research has promoted the exploration of the cochaperone cell division cycle 37 (CDC37) as a kinase-specific recognizer and has shown that the HSP90-CDC37-kinase complex is particularly relevant in cancers. Indeed, disrupting the HSP90-CDC37-kinase complex, rather than totally blocking the ATP function of HSP90, is emerging as an alternative way to avoid the limitations of current inhibitors. In this review, we first briefly introduce the HSP90-CDC37-kinase cycle and present the currently available approaches for inhibitor development targeting this cycle and provide insights into selective regulation of the kinase clients of HSP90 by more directional ways.
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http://dx.doi.org/10.1002/med.21807DOI Listing
April 2021

Insights into mechanisms involved in the uptake, translocation, and metabolism of phthalate esters in Chinese cabbage (Brassica rapa var. chinensis).

Sci Total Environ 2021 May 30;768:144945. Epub 2021 Jan 30.

MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China. Electronic address:

In the present study, the uptake and translocation mechanisms of phthalate esters (PAEs) and their primary mono esters metabolites (mPAEs), and the mechanisms of PAEs metabolism in plants were elucidated. The objectives of this study were to: (i) elucidate the fractionation of PAEs and mPAEs in Chinese cabbage (Brassica rapa var. chinensis) by hydroponic experiment, (ii) investigate the PAEs and mPAEs uptake mechanisms in root by inhibitor experiments, (iii) explain the molecular mechanisms of PAE interactions with the plant macromolecules by proteomics analysis and molecular docking, and (iv) reveal the involvement of carboxylesterase in the plant metabolism of PAEs. The results demonstrated that both the apoplastic and symplastic pathways contributed to the uptake of di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP) by vacuum-infiltration-centrifugation method. The energy-dependent active process was involved for the uptake of DnBP, DEHP, MnBP, and MEHP. The passive uptake pathways of anion mPAEs and neutral PAEs differ. Aquaporins contributed to the uptake of anion MnBP and MEHP, and slow-type anion channel was also responsible for the uptake of anion MEHP. Molecular interactions of PAEs and macromolecules were further characterized by proteomic analysis and molecular docking. PAEs were transferred via non-specific lipid transfer protein by binding hydroponic amino acid residues. The carboxylesterase enzyme was attributed to the metabolism of PAEs to form mPAEs by using crude enzyme extract and commercial pure enzyme. This study provides both experimental and theoretical evidence for uptake, accumulation, and metabolism of PAEs in plants.
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http://dx.doi.org/10.1016/j.scitotenv.2021.144945DOI Listing
May 2021

Analysis of the Characteristics of TIGIT-Expressing CD3CD56NK Cells in Controlling Different Stages of HIV-1 Infection.

Front Immunol 2021 26;12:602492. Epub 2021 Feb 26.

Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGITNK cells in acute infection was positively associated with HIV-1 viral load ( = 0.53, = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96CD226 cells diminished among total NK cells, TIGITNK and TIGITNK cells, while CD96CD226 cells expanded. Reduced CD96CD226 cells and elevated CD96CD226 cells among NK cells especially TIGITNK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2ANKG2CNK cells, with a significantly higher proportion than in NKG2ANKG2CNK cells. Moreover, the frequencies of TIGITNK cells were positively associated with the frequencies of NKG2ANKG2CNK cells in acute infection ( = 0.62, < 0.0001), chronic infection ( = 0.37, = 0.023) and healthy donors ( = 0.36, = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGITNK cells were detected compared to TIGITNK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGITNK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGITNK cells in both acute and chronic infection. Moreover, the functionalities of TIGITNK cells were lower than those of TIGITNK cells, except for TNF-αCD107aIFN-γNK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.
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http://dx.doi.org/10.3389/fimmu.2021.602492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953050PMC
February 2021

Corrigendum to 'Hydroxychloroquine inhibiting neutrophil extracellular trap formation alleviates hepatic ischemia/reperfusion by blocking TLR9 in mice' [Clinical Immunology 216 (2020) 108461].

Clin Immunol 2021 Apr 3;225:108681. Epub 2021 Feb 3.

Lanzhou University Second Hospital, Key Laboratory of Digestive System Tumors of Gansu Province, China. Electronic address:

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http://dx.doi.org/10.1016/j.clim.2021.108681DOI Listing
April 2021

Fossil data support a pre-Cretaceous origin of flowering plants.

Nat Ecol Evol 2021 04 28;5(4):449-457. Epub 2021 Jan 28.

CAS Key Laboratory of Tropical Forest Ecology, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, China.

Flowering plants (angiosperms) are the most diverse of all land plants, becoming abundant in the Cretaceous and achieving dominance in the Cenozoic. However, the exact timing of their origin remains a controversial topic, with molecular clocks generally placing their origin much further back in time than the oldest unequivocal fossils. To resolve this discrepancy, we developed a Bayesian method to estimate the ages of angiosperm families on the basis of the fossil record (a newly compiled dataset of ~15,000 occurrences in 198 families) and their living diversity. Our results indicate that several families originated in the Jurassic, strongly rejecting a Cretaceous origin for the group. We report a marked increase in lineage accumulation from 125 to 72 million years ago, supporting Darwin's hypothesis of a rapid Cretaceous angiosperm diversification. Our results demonstrate that a pre-Cretaceous origin of angiosperms is supported not only by molecular clock approaches but also by analyses of the fossil record that explicitly correct for incomplete sampling.
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http://dx.doi.org/10.1038/s41559-020-01387-8DOI Listing
April 2021

Unifying Molecular Weights of Highly Linear Polyethylene Waxes through Unsymmetrical 2,4-Bis(imino)pyridylchromium Chlorides.

Molecules 2020 Nov 27;25(23). Epub 2020 Nov 27.

Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

By dealing CrCl∙3THF with the corresponding ligands (-), an array of fluoro-substituted chromium (III) chlorides (-) bearing 2-[1-(2,4-dibenzhydryl-6-fluoro- phenylimino)ethyl]-6-[1-(arylimino)ethyl]pyridine (aryl = 2,6-MePh , 2,6-EtPh , 2,6-iPrPh , 2,4,6-MePh , 2,6-Et-4-MePh ) was synthesized in good yield and validated via Fourier Transform Infrared (FT-IR) spectroscopy and elemental analysis. Besides the routine characterizations, the single-crystal X-ray diffraction study revealed the solid-state structures of complexes and as the distorted-octahedral geometry around the chromium center. Activated by either methylaluminoxane (MAO) or modified methylaluminoxane (MMAO), all the chromium catalysts exhibited high activities toward ethylene polymerization with the MMAO-promoted polymerizations far more productive than with MAO (20.14 × 10 g (PE) mol (Cr) h vs. 10.03 × 10 g (PE) mol (Cr) h). In both cases, the resultant polyethylenes were found as highly linear polyethylene waxes with low molecular weights around 1-2 kg mol and narrow molecular weight distribution (MWD range: 1.68-2.25). In general, both the catalytic performance of the -fluorinated chromium complexes and polymer properties have been the subject of a detailed investigation and proved to be highly dependent on the polymerization reaction parameters (including cocatalyst type and amount, reaction temperature, ethylene pressure and run time).
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http://dx.doi.org/10.3390/molecules25235584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731025PMC
November 2020

Design, synthesis and bioevaluation of inhibitors targeting HSP90-CDC37 protein-protein interaction based on a hydrophobic core.

Eur J Med Chem 2021 Jan 22;210:112959. Epub 2020 Oct 22.

State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

HSP90-CDC37 protein-protein interaction (PPI) works as a kinase specific-molecular chaperone system to regulate the maturation of kinases. Currently, selectively disrupting HSP90-CDC37 PPI, rather than the direct inhibition of the ATPase function of HSP90, is emerging as a promising strategy for cancer therapy by specifically blocking the maturation of kinases. However, due to the limited understanding of HSP90-CDC37 binding interface, design of small molecule inhibitors targeting HSP90-CDC37 PPI is challenging. In this work, based on the binding mode of compound 11 (previously reported by our group), we discovered a hydrophobic pocket centered on Phe213, which was previously unknown, contributing to the binding affinity of HSP90-CDC37 PPI inhibitors. A series of hydrophobic substituted inhibitors were utilized to confirm the importance of Phe213 hydrophobic core. Finally, we obtained an optimum compound DDO-5994 (exhibited an ideal binding pattern on hydrophobic core) with improved binding affinity (K = 5.52 μM) and antiproliferative activity (IC = 6.34 μM). Both in vitro and in vivo assays confirmed DDO-5994 as a promising inhibitor to exhibit ideal antitumor efficacy through blocking HSP90-CDC37 PPI.
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http://dx.doi.org/10.1016/j.ejmech.2020.112959DOI Listing
January 2021

6-Arylimino-2-(2-(1-phenylethyl)naphthalen-1-yl)-iminopyridylmetal (Fe and Co) Complexes as Highly Active Precatalysts for Ethylene Polymerization: Influence of Metal and/or Substituents on the Active, Thermostable Performance of Their Complexes and Resultant Polyethylenes.

Molecules 2020 Sep 16;25(18). Epub 2020 Sep 16.

Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

A series of 6-arylimino-2-(2-(1-phenylethyl)naphthalen-1-yl)iminopyridines and their iron(II) and cobalt(II) complexes (-, -) were synthesized and routinely characterized as were and complexes, studied by single crystal X-ray crystallography, which individually displayed a distorted square pyramidal or trigonal bipyramid around a cobalt center. Upon treatment with either methyluminoxane (MAO) or modified methyluminoxane (MMAO), all complexes displayed high activities regarding ethylene polymerization even at an elevated temperature, enhancing the thermostability of the active species. In general, iron precatalysts showed higher activities than their cobalt analogs; for example, 10.9 × 10 g(PE) mol (Co) h by and 17.0 × 10 g(PE) mol (Fe) h by . Bulkier substituents are favored for increasing the molecular weights of the resultant polyethylenes, such as 25.6 kg mol obtained by and 297 kg mol obtained by . A narrow polydispersity of polyethylenes was observed by iron precatalysts activated by MMAO, indicating a single-site active species formed.
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http://dx.doi.org/10.3390/molecules25184244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570845PMC
September 2020

Alterations of CCR2 and CX3CR1 on Three Monocyte Subsets During HIV-1/ Coinfection.

Front Med (Lausanne) 2020 18;7:272. Epub 2020 Jun 18.

Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.

HIV-1/ () coinfection has become a global challenge, and three monocyte subsets express varying levels of the chemokine receptors CCR2 and CX3CR1. We recently evaluated the association between monocyte subsets and regulatory T cells in HIV-infected individuals with syphilis. Currently, the dynamic changes of CCR2 and CX3CR1 on monocyte subsets during HIV-1 and syphilis coinfection have not been fully investigated. In this study, cell surface staining was used to explore CCR2 and CX3CR1 expression on three monocyte subsets during HIV-1/ coinfection. We found that CCR2 densities on the classical monocyte subsets decreased in acute HIV-1 infected (AHI) patients, chronic HIV-1-infected individuals without antiviral therapy (ART) (CHI+ ART-), chronic HIV-1-infected individuals receiving ART (CHI+ART+), rapid plasma reagin-positive (RPR+) individuals, CHI+ ART- plus RPR+ (CHI+RPR+ ART-) individuals, and CHI+ART+ plus RPR (CHI+RPR+ART+) individuals. CX3CR1 density increased on the three monocyte subsets during HIV-1 and/or infection. CX3CR1 density on the intermediate and non-classical monocyte subsets in CHI+ ART- individuals was lower than that in CHI+ART+ individuals, and CX3CR1 density on the three monocyte subsets in CHI+ART+ individuals was higher than that in CHI+RPR+ART+ individuals. Our data provide new insight into the roles of CCR2 and CX3CR1 on three monocyte subsets in HIV-1 and pathogenesis.
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http://dx.doi.org/10.3389/fmed.2020.00272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314900PMC
June 2020

Bis-cycloheptyl-fused bis(imino)pyridine-cobalt catalysts for PE wax formation: positive effects of fluoride substitution on catalytic performance and thermal stability.

Dalton Trans 2020 Jul;49(27):9425-9437

Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. and CAS Research/Education Center for Excellence in Molecular Sciences and International School, University of Chinese Academy of Sciences, Beijing 100049, China and State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

The α,α'-bis(imino)-2,3:5,6-bis(pentamethylene)pyridyl-cobalt(ii) chlorides, [2,3:5,6-{C4H8C(N(2-R1-4-R3-6-R2C6H2))}2C5HN] CoCl2 (R1 = Me, R2 = R3 = CH(p-FPh)2Co1; R1 = Et, R2 = R3 = CH(p-FPh)2Co2; R1 = i-Pr, R2 = R3 = CH(p-FPh)2Co3; R1 = Cl, R2 = R3 = CH(p-FPh)2Co4; R1 = F, R2 = R3 = CH(p-FPh)2Co5; R1 = F, R2 = R3 = CHPh2Co5'', R1 = R2 = Me, R3 = CH(p-FPh)2Co6; R1 = R3 = Me, R2 = CH(p-FPh)2Co7), have been synthesized by a one-pot template reaction of α,α'-dioxo-2,3:5,6-bis(pentamethylene)pyridine, cobalt(ii) chloride and the respective aniline in n-butanol. By contrast, the mixed cobalt(ii) chloride/acetate complex, [2,3:5,6-{C4H8C(N(2-F-4,6-(CH(p-FPh)2)2C6H2))}2C5HN]CoCl(OAc) (Co5'), was isolated when the corresponding template reaction was carried out in acetic acid. Structural characterization of Co4, Co5 and Co5'' revealed distorted square pyramidal geometries while six-coordinate Co5', incorporating a chelating acetate ligand, exhibited a distorted octahedral geometry. On activation with either MAO or MMAO, 2-fluoride-4,6-bis{di(p-fluorophenyl)methyl}-substituted Co5 showed maximum catalytic activity for ethylene polymerization at a high operating temperature of 60 °C (up to 2.1 × 107 g (PE) mol-1 (Co) h-1), producing highly linear (Tms > 121 °C), low molecular weight polyethylene waxes (Mw range: 1.5-5.0 kg mol-1) with narrow dispersity (Mw/Mn range: 1.7-2.9). End-group analysis of the waxes reveals β-H elimination as the dominant chain transfer process.
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http://dx.doi.org/10.1039/d0dt01876gDOI Listing
July 2020

Pseudoginsenoside-F11 ameliorates ischemic neuron injury by regulating the polarization of neutrophils and macrophages in vitro.

Int Immunopharmacol 2020 Aug 21;85:106564. Epub 2020 May 21.

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, PR China. Electronic address:

Pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, has neuroprotective effects on permanent and transient cerebral ischemia in rats by alleviating autophagic/lysosomal defects and repressing calcium overload, respectively. Ischemic stroke triggers peripheral innate immune cells, mainly neutrophils and macrophages, to infiltrate the damaged brain. The polarization of neutrophils and macrophages after cerebral ischemia is essential for post-stroke damage/recovery. However, it remains elusive whether PF11 ameliorates ischemic neuron injury by regulating the polarization of neutrophils and macrophages. The present study demonstrated for the first time that conditioned media from ischemic neurons induced neutrophils and macrophages to polarize into N1 and M1 phenotypes, respectively. Furthermore, PF11 (30, 100 μM) inhibited the induction of N1 neutrophils by conditioned media from oxygen glucosedeprivation/re-oxygenation (OGD/R)-induced ischemic neurons and promoted the polarization of neutrophils to N2 phenotypes. In addition, PF11 (100 μM) attenuated the exacerbation of N1 neutrophils and facilitated the protection of N2 neutrophils on OGD/R-induced neuronal damage. Similarly, PF11 (100 μM) inhibited the induction of M1 macrophages by conditioned media from ischemic neurons and facilitated the polarization of macrophages to M2 phenotypes. What's more, PF11 (100 μM) attenuated the aggravation of M1 macrophages and promoted the protection of M2 macrophages on OGD/R-induced primary neuron injury. In summary, the present study indicates that PF11 ameliorates ischemic neuron damage by regulating neutrophils and macrophages polarization, suggesting that neutrophils and macrophages may be promising targets for the treatment of cerebral ischemia.
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http://dx.doi.org/10.1016/j.intimp.2020.106564DOI Listing
August 2020

Hydroxychloroquine inhibiting neutrophil extracellular trap formation alleviates hepatic ischemia/reperfusion injury by blocking TLR9 in mice.

Clin Immunol 2020 07 11;216:108461. Epub 2020 May 11.

Lanzhou University Second Hospital, Key Laboratory of Digestive System Tumors of Gansu Province, China. Electronic address:

Hepatic ischemia/reperfusion (I/R) injury may arise after partial hepatectomy and liver transplantation. Neutrophil extracellular traps (NETs) were involved in hepatic I/R injury. This study tested the hypothesis that blocking NETs formation could be a potential therapeutic target against hepatic I/R injury. NETs were excessively formed within liver and in serum of I/R mice models and were testified to be an independent contributor to hepatic I/R injury. Hydroxychloroquine (HCQ) alleviated hepatic I/R injury by inhibiting NETs formation in SCID and c57BL/6 mice models. In vitro, HCQ inhibited neutrophils to form NETs at a concentration of 100 μg/ml. CpG-ODN reversed the effect of HCQ inhibiting NETs formation. HCQ inhibited PAD4 and Rac2 expressions by blocking TLR9. NETs are essential contributors to hepatic I/R injury. HCQ blocking TLR9 protects against hepatic I/R injury by inhibiting NETs formation, which may suggest utility of HCQ or other TLR9 agonists for preventing hepatic I/R injury in clinical practices.
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http://dx.doi.org/10.1016/j.clim.2020.108461DOI Listing
July 2020

4,4'-Difluorobenzhydryl-modified bis(imino)-pyridyliron(ii) chlorides as thermally stable precatalysts for strictly linear polyethylenes with narrow dispersities.

Dalton Trans 2020 Jun;49(22):7384-7396

Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. and CAS Research/Education Center for Excellence in Molecular Sciences and International School, University of Chinese Academy of Sciences, Beijing 100049, China and State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

The 4,4'-difluorobenzhydryl-modified bis(imino)pyridylferrous chlorides, [2-{CMeN(2,6-(4-FC6H4)2CH2-4-t-BuC6H2)}-6-(CMeNAr)C5H3N] FeCl2 (Ar = 2,6-Me2C6H3Fe1, 2,6-Et2C6H3Fe2, 2,6-i-Pr2C6H3Fe3, 2,4,6-Me3C6H2Fe4, 2,6-Et-4-MeC6H2Fe5 and 2,6-(4-FC6H4)2CH2-4-t-BuC6H2Fe6), were synthesized in good yields. All iron complexes were characterized by 1H/19F NMR and elemental analysis, and the molecular structures of representative complexes Fe1 and Fe6 were determined by single crystal X-ray diffraction, which revealed a slightly distorted square pyramid around the iron center. Activated with either MAO or MMAO, Fe1-Fe5 exhibited very high activities (up to 17.2 × 106 g (PE) mol-1 (Fe) h-1 for Fe1/MMAO) toward ethylene polymerization, producing highly linear polyethylenes with narrow dispersities as required by industry and value added PEs. Importantly, the Fe1/MAO maintained an activity of 9.5 × 106 g (PE) mol-1 (Fe) h-1 at 100 °C of operating temperature, making the catalytic system suitable for practical application. Simulation quantitatively revealed the mechanism of the enhanced catalytic performance from the electronic and steric point of view.
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http://dx.doi.org/10.1039/d0dt01344gDOI Listing
June 2020

NKG2C+ natural killer cell function improves the control of HBV replication in individuals with acute HIV infection coinfected with HBV.

Medicine (Baltimore) 2020 May;99(18):e20073

Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University.

Individuals infected with hepatitis B virus (HBV) are often coinfected with human immunodeficiency virus (HIV). However, individuals with chronic HBV infection living with acute HIV infection have a significantly lower HBV viral load, along with higher HBeAg and HBsAg loss than HBV-infected individuals alone. Here, we investigated the possible role of natural killer cells (NK cell) function in this progressive course to explore the relationship between phenotypic/functional changes in NK cells during acute HIV infection and HBV clearance in patients with HIV/HBV coinfection.Peripheral blood NK cells from 38 patients with primary HIV infection, including 20 with untreated HIV infection and 18 treatment-naïve patients with HIV/HBV coinfection and 16 patients with chronic HBV infection, were enrolled in this study.We found that the HIV/HBV-coinfected individuals had higher levels of NK cells than the HBV-infected individuals, due to expansion of the CD56 NK cell population. The proportion of NK cells in CD56 and CD56 NK subsets was not found significant difference between HIV/HBV-coinfected and HBV-infected individuals. However, NKG2C levels on NK cells and subsets were significantly higher in HIV/HBV-coinfected individuals than in HBV-infected individuals, whereas NKG2A levels were unaffected or decreased. In addition, the levels of degranulation CD107a, cytotoxicity and IFN-γ production of NK cells were increased in HIV/HBV-coinfected individuals than in HBV-infected individuals. The level of IL-10 production of NK cells was decreased in HIV/HBV-coinfected individuals than in HBV-infected individuals. Furthermore, the level of HBV-DNA was inversely correlated with the proportion of NKG2C and NKG2CNKG2A NK cells, while positively correlated with the proportion of NKG2A and NKG2CNKG2A NK cells. IFN-γ production was inversely correlated with levels of HBV-DNA, but the CD107a expression and IL-10 production of NK cells were not correlated with HBV-DNA levels.These results demonstrate that the upregulation of NKG2C expression, but not of NKG2A expression on the surface of NK cells increases cytolytic capacity and the amounts of cytokines produced and may play a crucial role in HBV clearance during HIV/HBV-coinfection.
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http://dx.doi.org/10.1097/MD.0000000000020073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440068PMC
May 2020

High molecular weight polyethylenes of narrow dispersity promoted using bis(arylimino)cyclohepta[b]pyridine-cobalt catalysts ortho-substituted with benzhydryl & cycloalkyl groups.

Dalton Trans 2020 Apr;49(15):4774-4784

Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. and CAS Research/Education Center for Excellence in Molecular Sciences and International School, University of Chinese Academy of Sciences, Beijing 100049, China and State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

A one-pot template strategy has been utilized to synthesize sterically enhanced bis(imino)cyclohepta[b]pyridine-cobalt(ii) chlorides, [2-{(Ar)N[double bond, length as m-dash]CMe}-9-{N(Ar)}C10H10N]CoCl2 (Ar = 2-(C5H9)-4,6-(CHPh2)2C6H2Co1, 2-(C6H11)-4,6-(CHPh2)2C6H2Co2, 2-(C8H15)-4,6-(CHPh2)2C6H2Co3, 2-(C12H23)-4,6-(CHPh2)2C6H2Co4, 2,6-(C5H9)2-4-(CHPh2)C6H2Co5). All five complexes have been characterized by a combination of FT-IR spectroscopy, elemental analysis and single crystal X-ray diffraction. The molecular structures of Co1, Co3 and Co5 highlight the substantial steric hindrance imparted by the 2-cycloalkyl-6-benzhydryl or 2,6-dicyclopentyl ortho-substitution pattern; distorted square pyramidal geometries are exhibited in each case. On activation with methylaluminoxane (MAO) or modified methylaluminoxane (MMAO), all the complexes (apart from Co4/MAO) were active ethylene polymerization catalysts (up to 3.70 × 106 g PE per mol (Co) per h for Co5/MMAO), operating effectively at temperatures between 50 °C and 60 °C, producing polyethylenes with high molecular weights (up to 589.5 kg mol-1 for Co3/MAO). Furthermore, all polymers were highly linear (Tm > 130 °C) with narrow dispersities (Mw/Mn range: 2.0-3.0). The coexistence of two chain termination pathways, β-H elimination and transfer to aluminum, has been demonstrated using 13C/1H NMR spectroscopy.
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http://dx.doi.org/10.1039/d0dt00576bDOI Listing
April 2020

Discovery and Optimization of Small Molecules Targeting the Protein-Protein Interaction of Heat Shock Protein 90 (Hsp90) and Cell Division Cycle 37 as Orally Active Inhibitors for the Treatment of Colorectal Cancer.

J Med Chem 2020 02 24;63(3):1281-1297. Epub 2020 Jan 24.

State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization , China Pharmaceutical University , Nanjing 210009 , China.

Cell division cycle 37 (Cdc37) is known to work as a kinase-specific cochaperone, which selectively regulates the maturation of kinases through protein-protein interaction (PPI) with Hsp90. Directly disrupting the Hsp90-Cdc37 PPI is emerging as an alternative strategy to develop anticancer agents through a specific inhibition manner of kinase clients of Hsp90. Based on a first specific small-molecule inhibitor targeting Hsp90-Cdc37 PPI (), which was previously reported by our group, we conducted a preliminary investigation of the structure-activity relationships and pharmacodynamic evaluations to improve the potency and drug-like properties. Here, our efforts resulted in the currently best inhibitor with improved binding affinity ( = 0.5 μM) and cellular inhibitory activity (IC = 1.73 μM). Both in vitro and in vivo assays revealed that could efficiently block the Hsp90-Cdc37 interaction to specifically inhibit kinase clients of Hsp90. Furthermore, showed ideal physiochemical properties with favorable stability, leading to an oral efficacy in vivo.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01659DOI Listing
February 2020

Neutrophil extracellular traps activate lung fibroblast to induce polymyositis-related interstitial lung diseases via TLR9-miR-7-Smad2 pathway.

J Cell Mol Med 2020 01 10;24(2):1658-1669. Epub 2019 Dec 10.

Department of Rheumatology, Lanzhou University Second Hospital, Lanzhou, China.

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)-associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR-7 expression was down-regulated in lung tissue of PM group than control group, and NETs further decreased miR-7 expression. TLR9 and Smad2 were up-regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA-treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR-7 and Smad2 in LF. Finally, miR-7-Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM-related ILD, and TLR9-miR-7-Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.
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http://dx.doi.org/10.1111/jcmm.14858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991674PMC
January 2020

Foxp3Helios regulatory T cells are associated with monocyte subsets and their PD-1 expression during acute HIV-1 infection.

BMC Immunol 2019 10 24;20(1):38. Epub 2019 Oct 24.

Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.

Background: Helios has been reported to stabilize regulatory T (Treg) suppressive function. Programmed cell death protein 1 (PD-1) expression in three human monocyte subsets modulates immune responses. Recently, our team reported that three monocyte subsets are associated with T helper cell differentiation in HIV-1-infected patients. Until now, the effects of monocyte subsets and their PD-1 expression on Foxp3Helios Treg cells have not been fully characterized, especially during acute HIV-1 infection.

Results: The frequency of Foxp3HeliosCD45RA Treg cells is significantly higher in patients with acute HIV-1 infection than those of healthy controls and chronic HIV-1-infected patients undergoing combined antiretroviral therapy. The frequency of Foxp3HeliosCD45RA Treg cells is inversely correlated with CD4 T-cell counts and the CD4/CD8 ratio in chronic HIV-1-infected patients. During acute HIV-1 infection, the frequency of Foxp3HeliosCD45RA Treg cells is inversely correlated with the frequency of the intermediate CD14CD16 monocyte subset, but positively correlated with PD-1 expression in both intermediate CD14CD16 and non-classical CD14CD16 monocyte subsets.

Conclusions: In this study, the perturbations of Foxp3Helios Treg cells were characterized, and the association between monocyte subsets and their PD-1 expression and Foxp3Helios Treg cells was evaluated during HIV-1 infection. Our observations provide new evidence of the roles for Foxp3Helios Treg cells and PD-1 expression on monocyte subsets in HIV pathogenesis.
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http://dx.doi.org/10.1186/s12865-019-0319-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813100PMC
October 2019

Dialkylaluminum 2-substituted 6,6-dimethylcyclopentylpyridin-7-oxylates toward structural-differentiation of the ring-opening polymerization of ε-caprolactone and l-lactides.

Dalton Trans 2019 Mar;48(13):4157-4167

Beijing Key Laboratory of Clothing Materials R&D and Assessment, Beijing Engineering Research Center of Textile Nanofiber, School of Materials Science and Engineering, Beijing Institute of Fashion Technology, Beijing 100029, China.

Herein, a series of dialkylaluminum 2-substituted 6,6-dimethylcyclopentyl pyridin-7-oxylates Al1-Al7 were synthesized and characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. The molecular structure of Al3 was proven to be a dimer of an aluminum complex. These aluminum complexes could efficiently initiate the ring-opening polymerization (ROP) of ε-caprolactone (CL), and the structural differentiations of the resultant PCL were strongly dependent on the amount of BnOH (PhCH2OH) used. In the absence of BnOH, the resultant PCL showed a cyclic structure, whereas BnO-capped linear PCL was obtained in the presence of >2.0 equivalents of BnOH; the resultant PCL was a mixture of linear and cyclic PCLs in the presence of 1.0 equivalent of BnOH. Moreover, these aluminum complexes exhibited high efficiency towards the ROP of l-lactide (LLA); however, the activities were lower than those for the ROP of ε-CL. Without BnOH, the resultant PLLA showed a highly linear structure with the alkyl-end group from aluminum complexes; on the other hand, PLLA displayed a major cyclic structure and minor BnO-capped linear PLLA if 1.0 equivalent of BnOH was employed, and the percentage of BnO-capped linear PLLA was increased by increasing the amount of BnOH.
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http://dx.doi.org/10.1039/c9dt00137aDOI Listing
March 2019

Temperature-Responsive Electrocatalysis Based on Poly(N-Isopropylacrylamide)-Modified Graphene Oxide (PNIPAm-GO).

Chemistry 2019 Jan 27;25(6):1535-1542. Epub 2018 Dec 27.

College of Chemistry, Liaoning University, Shenyang, 110036, P.R. China.

Poly(N-isopropylacrylamide)-modified graphene oxide (PNIPAm-GO), which is a type of thermally responsive GO, was designed and synthesized through a covalent "grafting-from" strategy. The as-prepared modified nanosheets integrated the individual advantages of two components, such as the thermal sensitivity of the PNIPAm terminal as well as the conductivity and the open 2D structure of the GO substrate. PNIPAm-GO was able to perform the reversible regulation of hydrophilicity/hydrophobicity in aqueous solution upon variations in the temperature. Such a unique property might also lead to the utilization of PNIPAm-GO as an intelligent electrode material to achieve a switchable electrochemical response toward a [Fe(CN) ] probe. The PNIPAm-GO modified glassy carbon electrode (PNIPAm-GO/GC electrode) was able to exhibit better electrochemical performance in an ON/OFF switching effect than the PNIPAm-modified glassy carbon electrode (PNIPAm/GC electrode) without GO owing to the intrinsic properties and large surface area of the introduced GO. Moreover, it was found that the PNIPAm-GO/GC electrode also displayed excellent thermally responsive electrocatalysis toward the detection of 1,4-dihydro-β-nicotinamide adenine dinucleotide (NADH) and dopamine (DA), which resulted in two different catalytic statuses on the same electrode. This kind of switchable catalytic performance of the PNIPAm-GO/GC electrode might greatly enhance the flexibility of its application, and thus it is expected to have wide potential for applications in the fields of biosensors and biocatalysis.
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http://dx.doi.org/10.1002/chem.201804947DOI Listing
January 2019

Interface engineering: Surface hydrophilic regulation of LaFeO towards enhanced visible light photocatalytic hydrogen evolution.

J Colloid Interface Sci 2019 Feb 13;536:105-111. Epub 2018 Oct 13.

National Engineering Laboratory for Green Chemical Productions of Alcohols, Ethers and Esters, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, PR China. Electronic address:

The perovskite-type lanthanum ferrite, LaFeO, has emerged as one of the most promising candidates for highly efficient photocatalytic materials. However, the intrinsic drawbacks of inferior surface hydrophilicity (related to the absorption and transport of water), weak visible-light adsorption (related to the absorption of photon) and poor charge separation efficiency (related to the active substance that can actually participate in the reaction) seriously limit its photocatalytic efficiency. Herein, LaFeO is encapsulated by conductive polyaniline (PANI) aerogel on the surface to simultaneous moderate these deficiencies. The ameliorative surface properties and interface effect between LaFeO and PANI result in elevated effects for water adsorption and diffusion, visible-light (photon) adsorption and photo-induced carries transfer, and the coated LaFeO exhibits improved photocatalytic hydrogen evolution performance under visible light. In addition, after continuously testing, the coated LaFeO still shows superior stability with nearly negligible decay. Importantly, this model can enrich to other inorganic oxide based semiconductor to modulate the surface properties and charge transport behaviour, and hence improve the visible light photocatalytic performance.
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http://dx.doi.org/10.1016/j.jcis.2018.10.030DOI Listing
February 2019

Overvalued allelopathy and overlooked effects of humic acid-like substances on Microcystis aeruginosa and Scenedesmus obliquus competition.

Harmful Algae 2018 09 21;78:18-26. Epub 2018 Jul 21.

College of Natural Resources and Environment, Northwest A&F University, Yangling 712100, PR China; Collaborative Innovation Center of Water Security for Water Source Region of Mid-line of South-to-North Diversion Project of Henan Province, Nanyang Normal University, Nanyang, 473061, PR China; Department of Water Environment Research, Changjiang River Scientific Research Institute, Wuhan 430010, PR China. Electronic address:

To form Microcystis blooms, Microcystis must be competitively dominant to other phytoplankton species to produce enough biomass. The aim of this study was to determine the competition mechanisms between Microcystis aeruginosa and Scenedesmus obliquus. M. aeruginosa and S. obliquus were separately cultured in the filtrate of mono and mixed cultures of M. aeruginosa and S. obliquus with varying treatments concerning N, P and iron availability. The inhibition rate for M. aeruginosa was 20-31% when cultured in mono and mixed culture filtrates enriched with N and P, but this rate was reduced to -15 to 19% when cultured in filtrates enriched with N, P and iron. The inhibition rate for M. aeruginosa decreased from 80 to 100% to 11-39% in dialytic filtrates. However, there were no differences in inhibition rate for S. obliquus, regardless of filtrate or dialytic filtrate treatments. The potential allelochemical, 2-butyl-octanol (0.144 mg L), was found to have little inhibitory effect to M. aeruginosa or S. obliquus. Thus, previously reported allelopathy to Microcystis would be overestimated. We also report a new mechanism in phytoplankton competition in this study. The phytoplankton secreted humic acid-like substances that can reduce the bioavailability of iron, resulting in the inhibition of other phytoplankton.
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http://dx.doi.org/10.1016/j.hal.2018.07.003DOI Listing
September 2018

Photochemical oxidation of di-n-butyl phthalate in atmospheric hydrometeors by hydroxyl radicals from nitrous acid.

Environ Sci Pollut Res Int 2018 Nov 5;25(31):31091-31100. Epub 2018 Sep 5.

Institute of Atmospheric Environment and Pollution Control, School of Resource and Environmental Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China.

The photochemical oxidation of di-n-butyl phthalate (DBP) by OH radicals from nitrous acid (HONO) in atmospheric hydrometeors was explored by two techniques, steady-state irradiation, and laser flash photolysis (LFP). The effects of atmospheric liquid parameters on DBP transformation were systematically evaluated, showing that DBP does not react with HONO directly and OH-initiated reactions are crucial steps for consumption and transformation of DBP. Two reaction channels are operative: OH addition and hydrogen atom abstraction. The overall rate constant for the reaction of DBP with OH is 5.7 × 10 M s, and its specific rate constant for addition is 3.7 × 10 M s determined by using laser flash photolysis technique. Comparing the individual reaction rate constant for aromatic ring addition with the total rate constant, the majority of the OH radicals (about 65%) attack the aromatic ring. The major transformation products were identified by GC-MS, and the trends of their yields derived from both ring addition and H-abstraction with time are discussed. These results provide important insights into the photochemical transformation of DBP in atmospheric hydrometeors and contribute to atmospheric aerosol chemistry.
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http://dx.doi.org/10.1007/s11356-018-3091-yDOI Listing
November 2018

High-throughput and selective solid-phase extraction of urinary catecholamines by crown ether-modified resin composite fiber.

J Chromatogr A 2018 Aug 20;1561:48-55. Epub 2018 May 20.

School of Public Health, Tianjin Medical University, Tianjin 300070, China.

In the present study, we developed a simple and high-throughput solid phase extraction (SPE) procedure for selective extraction of catecholamines (CAs) in urine samples. The SPE adsorbents were electrospun composite fibers functionalized with 4-carboxybenzo-18-crown-6 ether modified XAD resin and polystyrene, which were packed into 96-well columns and used for high-throughput selective extraction of CAs in healthy human urine samples. Moreover, the extraction efficiency of packed-fiber SPE (PFSPE) was examined by high performance liquid chromatography coupled with fluorescence detector. The parameters affecting the extraction efficiency and impurity removal efficiency were optimized, and good linearity ranging from 0.5 to 400 ng/mL was obtained with a low limit of detection (LOD, 0.2-0.5 ng/mL) and a good repeatability (2.7%-3.7%, n = 6). The extraction recoveries of three CAs ranged from 70.5% to 119.5%. Furthermore, stable and reliable results obtained by the fluorescence detector were superior to those obtained by the electrochemical detector. Collectively, PFSPE coupled with 96-well columns was a simple, rapid, selective, high-throughput and cost-efficient method, and the proposed method could be applied in clinical chemistry.
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http://dx.doi.org/10.1016/j.chroma.2018.05.041DOI Listing
August 2018

WWP2 is a physiological ubiquitin ligase for phosphatase and tensin homolog (PTEN) in mice.

J Biol Chem 2018 06 23;293(23):8886-8899. Epub 2018 Apr 23.

From the State Key Laboratory of Proteomics, National Center of Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China,

The tumor suppressor phosphatase and tensin homolog (PTEN) plays a central role in regulating phosphatidylinositol 3-kinase (PI3K) signaling, and its gene is very frequently mutated in various human cancers. Numerous studies have revealed that PTEN levels are tightly regulated by both transcriptional and posttranslational modifications, with especially ubiquitylation significantly regulating PTEN protein levels. Although several ubiquitin ligases have been reported to mediate PTEN ubiquitylation , the ubiquitin ligase that promotes PTEN degradation has not been reported. Here we took advantage of specific knockout mouse models to demonstrate that WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) promotes PTEN degradation under physiological conditions, whereas another ubiquitin ligase, carboxyl terminus of Hsp70-interacting protein (CHIP), had no such effect. WWP2 knockout mice exhibited reduced body size, elevated PTEN protein levels, and reduced phosphorylation levels of the serine/threonine kinase and PTEN target AKT. In contrast, we observed no elevation of PTEN protein levels in CHIP knockout tissues and mouse embryonic fibroblasts. Furthermore, PTEN protein levels in CHIP/WWP2 double knockout mice were very similar to those in WWP2 single knockout mice and significantly higher than in WT and CHIP knockout mice. Our results demonstrate that WWP2, rather than CHIP, is an ubiquitin ligase that promotes PTEN degradation Considering PTEN's significant role in tumor development, we propose that WWP2 may be a potential target for fine-tuning PTEN levels in anticancer therapies.
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http://dx.doi.org/10.1074/jbc.RA117.001060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995496PMC
June 2018

Differential transcriptome analysis of zebrafish (Danio rerio) larvae challenged by Vibrio parahaemolyticus.

J Fish Dis 2018 Jul 23;41(7):1049-1062. Epub 2018 Mar 23.

Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China.

Zebrafish embryo and larva represent a useful in vivo model for identification of host innate immune responses to bacterial infection. Vibrio parahaemolyticus is a typical zoonotic pathogen worldwide that causes acute gastroenteritis in humans and vibriosis in fishes. However, the mechanism of the innate immune response in the zebrafish larvae infected by V. parahaemolyticus has not been clear. We analysed the transcriptomic profile of 3 days post-fertilization (dpf) zebrafish larvae immersed in V. parahaemolyticus 13 (Vp13) strain suspension for 2 hr. A total of 602 differentially expressed genes (DEGs) were identified in the infection group, of which 175 (29.07%) genes were upregulated and 427 (70.93%) genes were downregulated. These altered genes encoded complement and coagulation cascades, chemokine, TNF signalling pathway, NF-κB signalling pathway and JAK-STAT signalling pathway. Some significant DEGs, such as mmp13, cxcr4a, ccl20, hsp70, gngt, serpina1l, il8, cofilin and il11, were subjected to quantitative gene expression analysis, and the results were consistent with those of the transcriptome profile. These results clearly demonstrated that exposure to V. parahaemolyticus for 2 hr could activate innate immune response in 3dpf larvae by altered expression of downstream signalling pathway genes of pattern recognition receptors (PRRs). Our results also provide a useful reference for future analysis of signal transduction pathways and pathogenesis mechanisms underlying the systemic innate immune response to the external bacteria of V. parahaemolyticus.
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http://dx.doi.org/10.1111/jfd.12796DOI Listing
July 2018

Dexmedetomidine Alleviates Hyperoxia-Induced Acute Lung Injury via Inhibiting NLRP3 Inflammasome Activation.

Cell Physiol Biochem 2017 3;42(5):1907-1919. Epub 2017 Aug 3.

Department of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Background/aims: Dexmedetomidine (Dex), a specific agonist of α2-adrenoceptor, has been reported to have extensive pharmacological effects. In this study, we focused on the protective effect of Dex on hyperoxia-induced acute lung injury and further explored its possible molecular mechanisms.

Methods: The model of hyperoxia-induced acute lung injury was established by continuous inhalation of oxygen (FiO2= 0.90) for 7 d in neonatal rats in vivo. The in vitro experiments were carried out in LPS/ATP or hyperoxia-treated RAW264.7 cells. ELISA, western blot, TUNEL staining, and immunohistochemistry staining assays were performed and the commercial kits were used to assess the beneficial effect of Dex on hyperoxia-induced acute lung injury.

Results: According to our results, Dex treatment attenuated hyperoxia-induced acute lung injury via decreasing the lung wet/dry(W/D) weight ratio and mitigating pathomorphologic changes. Moreover, the oxidative stress injury, inflammatory reaction, and apoptosis in lung epithelial cells were inhibited by Dex treatment. In addition, the activation of NLRP3 inflammasome was restrained by Dex both in lung tissue in vivo and RAW264.7 cells in vitro.

Conclusion: These data provide evidence that Dex may ameliorate hyperoxia-induced acute lung injury, which suggests a potential clinical application of Dex in long-term supplemental oxygen therapy.
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http://dx.doi.org/10.1159/000479609DOI Listing
November 2017

Syphilis Infection Differentially Regulates the Phenotype and Function of γδ T Cells in HIV-1-Infected Patients Depends on the HIV-1 Disease Stage.

Front Immunol 2017 21;8:991. Epub 2017 Aug 21.

Beijing Key Laboratory for HIV/AIDS Research, Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.

A rapidly escalating outbreak of syphilis infection has been affected men who have sex with men, particularly those with HIV-1 infection. γδ T cells are unconventional immune cells with two main subsets, Vδ1 T cells and Vδ2 T cells, which possess a combination of innate and adaptive immune features allowing them against HIV-1. However, whether syphilis infection affects the phenotype and function of γδ T cells in HIV-1-infected patients remains unclear, especially in acute HIV-1 infection (AHI). In this study, we enrolled 57 HIV-1-infected patients (24 with HIV-1 infection only and 33 coinfected with syphilis) from an acute HIV-1-infected cohort in Beijing (PRIMO). A comprehensive analysis of γδ T-cell phenotype and function was performed by flow cytometry. We found syphilis coinfection could reverse the imbalance of Vδ1/Vδ2 ratio in AHI. Syphilis infection results in decreased γδ T-cell activation in AHI, but increased γδ T-cell activation in chronic HIV-1 infection (CHI). Moreover, patients with CHI had larger numbers of IL-17-producing γδ T cells than those with AHI, regardless of syphilis status. Thus, syphilis affected the γδ T-cell immune response differently in patients depending on the stages of HIV-1 disease. In addition, the percentage of IL-17-producing γδ T cells was positively correlated with the percentage of neutrophils. These results suggest that the γδ T-cell/IL-17/neutrophil axis is involved in HIV-1 pathogenesis and disease progression. Taken together, our observations provide new insight into the roles of γδ T cells in immunopathogenesis of syphilis and HIV-1 coinfection, particularly during AHI, and our findings may be helpful for the prevention of syphilis and other sexually transmitted infections and highlight the great significance on the remedy of patients coinfected with HIV-1.
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http://dx.doi.org/10.3389/fimmu.2017.00991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566620PMC
August 2017

Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells.

Oncotarget 2017 Mar;8(12):18832-18847

Union Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, China.

Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive. We demonstrate for the first time that supranutritional dose of selenite suppresses glutaminolysis by promoting GLS1 protein degradation and apoptosis. Mechanistically, selenite promotes association of APC/C-CDH1 with GLS1 and leads to GLS1 degradation by ubiquitination, this process is related to induction of PTEN expression. In addition, GLS1 expression is increased in human colorectal cancer tissues compared with normal mucosae. Our data provide a novel mechanistic explanation for the anti-cancer effect of selenite from a perspective of cell metabolism. Moreover, our results indicate that glutaminolysis especially GLS1 could be an attractive therapeutic target in colorectal cancer.
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http://dx.doi.org/10.18632/oncotarget.13600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386651PMC
March 2017

Aluminum trichloride inhibits osteoblastic differentiation through inactivation of Wnt/β-catenin signaling pathway in rat osteoblasts.

Environ Toxicol Pharmacol 2016 Mar 8;42:198-204. Epub 2015 Dec 8.

College of Veterinary Medicine, Northeast Agricultural University, NO. 59 Mucai Street, Xiangfang District, Harbin 150030, China. Electronic address:

Exposure to aluminum (Al) suppresses bone formation. Osteoblastic differentiation plays a key role in the process of bone formation. However, the effect of Al on osteoblastic differentiation is still controversial, and the mechanism remains unclear. To investigate the effect of Al on osteoblastic differentiation and whether Wnt signaling pathway was involved in it, the primary rat osteoblasts were exposed to 1/40 IC50, 1/20 IC50 and 1/10 IC50 of aluminum trichloride (AlCl3) for 24h, respectively. The activity analysis of alkaline phosphate, qRT-PCR analysis of type I collagen, alkaline phosphate, Wnt3a and Dkk-1, Western blot analysis of p-GSK3β, GSK3β and β-catenin protein and Immunofluorescence staining for β-catenin suggested that AlCl3 inhibited osteoblastic differentiation and Wnt/β-catenin pathway. Moreover, we found exogenous Wnt3a application reversed the inhibitory effect of AlCl3 on osteoblastic differentiation, accompanied by activating the Wnt/β-catenin pathway. Taken together, these findings suggest that AlCl3 inhibites osteoblastic differentiation through inactivation of Wnt/β-catenin pathway in osteoblasts.
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http://dx.doi.org/10.1016/j.etap.2015.11.023DOI Listing
March 2016