Synthesis, properties, calculations and applications of small molecular host materials containing oxadiazole units with different nitrogen and oxygen atom orientations for solution-processable blue phosphorescent OLEDs

Hua Ye,Hongyu Wu,Liangyuan Chen,Songhua Ma,Kaifeng Zhou,Guobing Yan,Jiazhong Shen,Dongcheng Chen,Shi‑Jian Su 대한금속·재료학회 2018 ELECTRONIC MATERIALS LETTERS Vol.14 No.2

A series of new small molecules based on symmetric electron-acceptor of 1,3,4-oxadiazole moiety or its asymmetric isomerof 1,2,4-oxadiazole unit were successfully synthesized and applied to solution-processable blue phosphorescent organic lightemittingdiodes for the first time, and their thermal, photophysical, electrochemical properties and density functional theorycalculations were studied thoroughly. Due to the high triplet energy levels (ET, 2.82–2.85 eV), the energy from phosphorescentemitter of iridium(III) bis[(4,6-difluorophenyl)-pyridinate-N,C2′]picolinate (FIrpic) transfer to the host molecules couldbe effectively suppressed and thus assuring the emission of devices was all from FIrpic. In comparison with the para-modeconjugation in substitution of five-membered 1,3,4-oxadiazole in 134OXD, the meta-linkages of 1,2,4-isomer appending withtwo phenyl rings cause the worse conjugation degree and the electron delocalization as well as the lower electron-withdrawingability for the other 1,2,4-oxadiazole-based materials. Noting that the solution-processed device based on 134OXD containing1,3,4-oxadiazole units without extra vacuum thermal-deposited hole/exciton-blocking layer and electron-transportinglayer showed the highest maximum current efficiency (CEmax) of 8.75 cd/A due to the excellent charge transporting ability of134OXD, which far surpassed the similar devices based on other host materials containing 1,2,4-oxadiazole units. Moreover,the device based on 134OXD presented small efficiency roll-off with current efficiency (CE) of 6.26 cd/A at high brightnessup to 100 cd/m2. This work demonstrates different nitrogen and oxygen atom orientations of the oxadiazole-based hostmaterials produce major impact on the optoelectronic characteristics of the solution-processable devices.

Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling

Zhu Tao,Zhang Hong,Li Sijie,Wu Kaifeng,Yin Yibing,Zhang Xuemei 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Leukemia is caused by the malignant clonal expansion of hematopoietic stem cells, and in adults, the most common type of leukemia is acute myeloid leukemia (AML). Autophagy inhibitors are often used in preclinical and clinical models in leukemia therapy. However, clinically available autophagy inhibitors and their efficacy are very limited. More effective and safer autophagy inhibitors are urgently needed for leukemia therapy. In a previous study, we showed that ΔA146Ply, a mutant of pneumolysin that lacks hemolytic activity, inhibited autophagy of triple-negative breast cancer cells by activating mannose receptor (MR) and toll-like receptor 4 (TLR4) and that tumor-bearing mice tolerated ΔA146Ply well. Whether this agent affects AML cells expressing TLR4 and MR and the related mechanisms remain to be determined. In this study, we found that ΔA146Ply inhibited autophagy and induced apoptosis in AML cells. A mechanistic study showed that ΔA146Ply inhibited autophagy by activating mammalian target of rapamycin signaling and induced apoptosis by inhibiting autophagy. ΔA146Ply also inhibited autophagy and induced apoptosis in a mouse model of AML. Furthermore, the combination of ΔA146Ply and chloroquine synergistically inhibited autophagy and induced apoptosis in vitro and in vivo. Overall, this study provides an alternative effective autophagy inhibitor that may be used for leukemia therapy.

SP0454, A Putative Threonine Dehydratase, Is Required For Pneumococcal Virulence In Mice

WenJuan Yan,Hong Wang,WenChun Xu,KaiFeng Wu,Run Yao,XiuYu Xu,Jie Dong,YanQing Zhang,Wen Zhong,XueMei Zhang 한국미생물학회 2012 The journal of microbiology Vol.50 No.3

Increasing pressure in antibiotic resistance and the requirement for the design of new vaccines are the objectives of clarifying the putative virulence factors in pneumococcal infection. In this study, the putative threonine dehydratase sp0454 was inactivated by erythromycin-resistance cassette replacement in Streptococcus pneumoniae CMCC 31203 strain. The sp0454 mutant was tested for cell growth, adherence, colonization, and virulence in a murine model. The Δsp0454 mutant showed decreased ability for colonization and impaired ability to adhere to A549 cells. However, the SP0454 polypeptide or its antiserum did not affect pneumococcal CMCC 31203 adhesion to A549 cells. The sp0454 deletion mutant was less virulent in a murine intranasal infection model. Real-time RT-PCR analysis revealed significant decrease of the pneumococcal surface antigen A expression in the sp0454 mutant. These results suggest that SP0454 contributes to virulence and colonization, which could be explained in part by modulating the expression of other virulence factors, such as psaA in pneumococcal infection.

Serotype-Independent Protection against Pneumococcal Infections Elicited by Intranasal Immunization with Ethanol-Killed Pneumococcal Strain, SPY1

XiuYu Xu,Qun Zhang,Jiangping Meng,Yiping Wang,Jie Zheng,Kaifeng Wu,Xuemei Zhang,Yibing Yin 한국미생물학회 2014 The journal of microbiology Vol.52 No.4

The 23-valent polysaccharide vaccine and the 7-valent pneumococcalconjugate vaccine are licensed vaccines that protectagainst pneumococcal infections worldwide. However,the incidence of pneumococcal diseases remains high in lowincomecountries. Whole-cell vaccines with high safety andstrong immunogenicity may be a favorable choice. We previouslyobtained a capsule-deficient Streptococcus pneumoniaemutant named SPY1 derived from strain D39. As anattenuated live pneumococcal vaccine, intranasal immunizationwith SPY1 elicits broad serotype-independent protectionagainst pneumococcal infection. In this study, forsafety consideration, we inactivated SPY1 with 70% ethanoland intranasally immunized BALB/c mice with killed SPY1plus cholera toxin adjuvant for four times. Results showedthat intranasal immunization with inactivated SPY1 inducedstrong humoral and cellular immune responses. Intranasalimmunization with inactivated SPY1 plus cholera toxin adjuvantelicited effective serotype-independent protection againstthe colonization of pneumococcal strains 19F and 4 as well aslethal infection of pneumococcal serotypes 2, 3, 14, and 6B. The protection rates provided by inactivated SPY1 againstlethal pneumococcal infection were comparable to those ofcurrently used polysaccharide vaccines. In addition, vaccinespecificB-cell and T-cell immune responses mediated theprotection elicited by SPY1. In conclusion, the 70% ethanolinactivatedpneumococcal whole-cell vaccine SPY1 is a potentiallysafe and less complex vaccine strategy that offersbroad protection against S. pneumoniae.

Effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver

Huan Yang,Ying Wang,Chi Ma,Chuan Sun,Yingchun Liu,Kaifeng Wu,Ming Li,Gerelt Borjigin,Feng Gao 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.2

Objective: An experiment was conducted to investigate the effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver. Methods: Eighteen time-mated ewes with singleton fetuses were allocated to three groups: restricted group 1 (RG1, 0.18 MJ ME/kg W0.75 d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/kg W0.75 d), n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/kg W0.75 d, n = 6). The feed restriction period was from 90 days to 140 days of pregnancy. Results: The ewe’s body weight, liver weights, water, and protein content of liver in the restricted groups were reduced compared with the CG group (p<0.05), but the liver fat contents in the RG1 group were higher than those of the CG group (p<0.05). The increased hepatic collagen fibers and reticular fibers were observed in the restricted groups with the reduction of energy intake. The concentrations of nonesterified free fatty acids in the RG1 and RG2 groups were higher than those of the CG group with the reduction of energy intake (p<0.05), but there were decreased concentrations of lipoprotein lipase and hepatic lipase in both restricted groups compared with the CG group (p<0.05). In addition, the increased concentrations of β-hydroxybutyric acid, triglycerides, malondialdehyde, total antioxidant capacity and activities of superoxide dismutase activity and catalase were found in the RG1 group, and the concentrations of cholinesterase in the RG1 group were reduced compared with the CG group (p<0.05). For the concentrations of acute phase proteins, the C-reactive protein (CRP) in the RG1 group were reduced compared with the CG group, but there were no differences in haptoglobin relative to the controls (p>0.05). Conclusion: The fat accumulation, increased hepatic fibrosis, antioxidant imbalance and modified synthesis of acute phase proteins were induced in ewe’s liver by maternal malnutrition during late pregnancy, which were detrimental for liver function to accommodate pregnancy.

Effects of maternal undernutrition during late pregnancy on the regulatory factors involved in growth and development in ovine fetal perirenal brown adipose tissue

Yang Huan,Ma Chi,Zi Yang,Zhang Min,Liu Yingchun,Wu Kaifeng,Gao Feng 아세아·태평양축산학회 2022 Animal Bioscience Vol.35 No.7

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/ enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition. Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT).Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW^0.75/d, n = 6), and a control group (CG, <i>ad libitum</i>, 0.67 MJ ME/kg BW^0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure.Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of <i>CyclinA</i> (p = 0.0109), <i>CyclinB</i> (p = 0.0019), <i>CyclinD</i> (p = 0.0015), cyclin-dependent kinase 1 (<i>CDK1</i>) (p = 0.0001), E2F transcription factor 1 (<i>E2F1</i>) (p = 0.0323), <i>E2F4</i> (p = 0.0101), and <i>E2F5</i> (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/ enhancer-binding protein-α (<i>C/EBPα</i>) (p = 0.0307) in RG2 and decreased <i>PPARγ</i> mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (<i>BMP4</i>) (p = 0.0083) and <i>BMP7</i> (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (<i>PGC-1α</i>) reduced in RG2 and RG1.Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

Pneumococcal wall teichoic acid is required for the pathogenesis of Streptococcus pneumoniae in murine models

Hongmei Xu,Libin Wang,Jian Huang,YanQing Zhang,Feng Ma,Jianmin Wang,WenChun Xu,XueMei Zhang,YiBing Yin,KaiFeng Wu 한국미생물학회 2015 The journal of microbiology Vol.53 No.2

Pneumococcal asymptomatic colonization of the respiratory tracts is a major risk for invasive pneumococcal disease. We have previously shown that pneumococcal wall teichoic acid (WTA) was involved in pneumococcal infection of sepsis and adherence to epithelial and endothelial cells. In this study, we investigated the contribution of pneumococcal WTA to bacterial colonization and dissemination in murine models. The result showed that nasopharynx colonizing D39 bacterial cells have a distinct phenotype showing an increased exposure of teichoic acids relative to medium-grown bacteria. The WTA-deficient mutants were impaired in their colonization to the nasopharynx and lungs, and led to a mild inflammation in the lungs at 36 h post-inoculation. Pretreatment of the murine nares with WTA reduced the ability of wild type D39 bacteria to colonize the nasopharynx. In addition, the WTA-deficient strain was impaired in its ability to invade the blood and brain following intranasal administration. WTA-deficient D39 strain was reduced in C3 deposition but was more susceptible to the killing by the neutrophils as compared with its parent strain. Our results also demonstrated that the WTA enhanced pneumococcal colonization and dissemination independently of the host strains. These results indicate that WTA plays an important role in pneumococcal pathogenesis, both in colonization and dissemination processes.