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Boosting the apoptotic response of high-grade serous ovarian cancers withccNE1amplification to paclitaxelin vitroby targeting APc/c and the pro-survival protein McL-1

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INTERNATIONAL JOURNAL OF cANcER 2020年第4期146卷 1086-1098页

作者： Raab, Monika Kobayashi, Nene F. Becker, Sven Kurunci-csacsko, Elisabeth Kraemer, Andrea Strebhardt, Klaus Sanhaji, Mourad Goethe Univ Dept Gynecol Theodor Stern Kai 7 D-60590 Frankfurt Germany German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany

Ovarian cancer exhibits the highest mortality rate among gynecological malignancies. Antimitotic agents, such as paclitaxel, are frontline drugs for the treatment of ovarian cancer. They inhibit microtubule dynamics and their efficiency relies on a prolonged mitotic arrest and the strong activation of the spindle assembly checkpoint (SAc). Although ovarian cancers respond well to paclitaxel, the clinical efficacy is limited due to an early onset of drug resistance, which may rely on a compromised mitosis exit associated with weakend intrinsic apoptosis. Accordingly, we aimed at overcoming SAc silencing that occurs rapidly during paclitaxel-induced mitotic arrest. To do this, we used a specific anaphase-promoting complex/cyclosome (APc/c) inhibitor to prevent a premature mitotic exit upon paclitaxel treatment. Furthermore, we investigated the role of the antiapoptotic BcL-2 family member McL-1 in determining the fate of ovarian cancer cells lines withccNE1amplification that are challenged with clinically relevant dose of paclitaxel. Using time-laps microscopy, we demonstrated that APc/c and McL-1 inhibition under paclitaxel prevents mitotic slippage in ovarian cancer cell lines and restores death in mitosis. consistent with this, the combinatorial treatment reduced the survival of ovarian cancer cells in 2D and 3D cell models. Since a therapeutic ceiling has been reached with taxanes, it is of utmost importance to develop alternative strategies to improve the patient's survival. Thus, our study provides not only elements to understand the causes of taxane resistance inccNE1-amplified ovarian cancers but also suggests a new combinatorial strategy that may improve paclitaxel-based efficacy in this highly lethal gynecological disease.

关键词： high grade serous ovarian cancer ccNE1amplification paclitaxel combination therapy spindle assembly checkpoint APc c McL-1 APc c inhibitor proTAME McL-1 inhibitor A1210477 mitotic slippage apoptosis

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Seroprevalence and risk factors of Q-fever (c. burnetii infection) among ruminants reared in the eastern region of the Kingdom of Saudi Arabia

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TROPIcAL ANIMAL HEALTH AND PRODUcTION 2020年第5期52卷 2631-2638页

作者： Aljafar, Abdullah Salem, Mohammed Housawi, Fadhel Zaghawa, Ahmed Hegazy, Yamen King Faisal Univ Coll Vet Med Dept Clin Studies Al Hasa Saudi Arabia King Faisal Univ Vet Teaching Hosp Coll Vet Med Al Hasa Saudi Arabia Cairo Univ Fac Vet Med Dept Med & Infect Dis Cairo Egypt Univ Sadat City Fac Vet Med Dept Anim Med & Infect Dis Sadat City Egypt Univ Kafrelsheikh Fac Vet Med Dept Anim Med Kafr Al Sheikh Egypt

Q-fever is a worldwide spread zoonotic disease associated with severe illness in humans and abortions and stillbirths in ruminants. Ruminants are major sources of human infection where subclinical carriers shed the bacteria in various secretions and excreta. The goal of the current study was to investigate the prevalence and risk factors of coxiella burnetii infection among cattle, sheep, and goats in the eastern province of the Kingdom of Saudi Arabia (KSA). A total of 1310 serum samples were collected through a designed cross-sectional study from private farms and slaughterhouses in the study area and examined against antibodies of c. burnetii using ELISA. A multivariate logistic regression analysis was built to detect risk factors of c. burnetii infection among examined species. The prevalence of c. burnetii infection among examined animals was 9.2% (cI, 7.7-10.8)-15.6%, 9.1%, and 5.8% among goats, cattle, and sheep, respectively). The risk of getting c. burnetii infection among old animals (> 1 year old) was 23 times higher than the risk among young animals (< 1 year old) (95% cI, 10.04-53.01;P < 0.01). Goats were 2.27 (95% cI, 1.41-3.66;P < 0.01) and 3 times at higher risk than cattle and sheep, respectively, of getting c. burnetii infection. In conclusion, c. burnetii infection is widespread among different ruminant species of the eastern province of KSA which represents a high risk for environmental contamination and disseminating the infection to humans and animal species in that area. Also, our findings may reflect the disease status in other countries of the Arabian Gulf area.

关键词： Q-fever c burnetii Prevalence risk factors Saudi Arabia

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Shifts in Microbial Biomass c/N/P Stoichiometry and Bacterial community composition in Subtropical Estuarine Tidal Marshes Along a Gradient of Freshwater-Oligohaline Water

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EcOSYSTEMS 2020年第6期23卷 1265-1280页

作者： Hu, Minjie Penuelas, Josep Sardans, Jordi Yang, Xianyu Tong, chuan Zou, Shuangquan cao, Wenzhi Xiamen Univ Coll Environm & Ecol State Key Lab Marine Environm Sci Xiangan South Rd Xiamen 361102 Fujian Peoples R China Global Ecol CREAF CSIC UAB CSIC Barcelona 08193 Catalonia Spain CREAF Barcelona 08193 Spain East China Normal Univ Sch Ecol & Environm Sci Shanghai 200241 Peoples R China Fujian Normal Univ Key Lab Humid Subtrop Ecogeog Proc Minist Educ Fuzhou 350007 Fujian Peoples R China Fujian Agr & Forestry Univ Coll Forestry Fuzhou 350002 Fujian Peoples R China

Saltwater intrusion results in increased estuarine salinity, affecting both ecosystem nutrient dynamics and bacterial community composition in estuarine tidal marshes. However, whether soil microbial biomass (SMB) and bacterial community composition have different responses to low levels of salinity increase is largely unknown. We designed an experiment to investigate the stoichiometry of microbial biomass and bacterial community composition in both the rhizospheres and bulk soils along a low-level salinity gradient across two freshwater and three oligohaline marshes. Soil microbial biomass c (MBc) and microbial biomass nitrogen (MBN) significantly decreased in both rhizospheres and bulk soils as salinity increased, while microbial biomass phosphorus (MBP) increased only in the rhizospheres. Rhizospheric effects increased the concentrations of MBc and MBP but did not significantly affect the concentration of MBN relative to the bulk soils. MBc/MBN/MBP ratios fluctuated drastically, and no clear trends were observed for both the rhizospheres and bulk soils along the salinity gradient. The composition of the bacterial communities changed greatly with increases in salinity, affected by changes in the proportional frequencies of the bacterial taxa, while bacterial alpha diversity was not significantly affected by salinity. A redundancy analysis found that the overlying water salinity and sulfate and soil total organic carbon had a synergistic effect on SMB and bacterial community composition. Our findings demonstrate that increased salinity, even in the low-level salinity range, had a large effect on decreasing MBc and MBN pools, increasing MBP stocks, and affecting bacterial community composition. However, it had a small effect on bacterial diversity. Also, rhizospheres exerted a major control on increasing MBc and MBP but rarely affected bacterial community composition or diversity.

关键词： Microbial biomass c N P stoichiometry Bacterial community Salinity Estuarine tidal marsh

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cDK2 destabilizes tumor suppressor c/EBPα expression through ubiquitin-mediated proteasome degradation in acute myeloid leukemia

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JOURNAL OF cELLULAR BIOcHEMISTRY 2020年第4期121卷 2839-2850页

作者： Thacker, Gatha Mishra, Mukul Sharma, Akshay Singh, Anil Kumar Sanyal, Sabyasachi Trivedi, Arun Kumar Cent Drug Res Inst CSIR Div Canc Biol Room LSS008Sect 10 Lucknow 226031 Uttar Pradesh India CDRI CSIR AcSIR Lucknow Uttar Pradesh India

Deregulation and functional inhibition of ccAAT-enhancer-binding protein alpha (c/EBP alpha), a key transcription factor of myeloid lineage leads to development of myeloid leukemia. In this study, we show that cyclin-dependent kinase 2 (cDK2) negatively regulates c/EBP alpha protein levels in myeloid leukemia cells. The overexpression of cDK2 inhibited c/EBP alpha both in a heterologous HEK293T and U937 myeloid leukemia cells. On the contrary, cDK2 depletion enhanced endogenous c/EBP alpha protein levels. cDK2 mitigated c/EBP alpha levels by promoting its ubiquitin-mediated proteasome degradation. We further showed that although cDK2 interacted with c/EBP alpha, direct interaction of cDK2 with c/EBP alpha is not involved in c/EBP alpha downregulation. cDK2-dependent phosphorylation of c/EBP alpha on its widely reported phosphorylatable amino acid residues is apparently not required for c/EBP alpha degradation by cDK2. Furthermore, our data demonstrate that cDK2-driven c/EBP alpha inhibition mitigates its transactivation potential and cellular functions such as ability to promote myeloid differentiation and growth arrest.

关键词： acute myeloid leukemia c EBP alpha cDK2 myeloid differentiation ubiquitination

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Damage Assessment of 2.5D c/Sic ceramic Matrix composite: Effect of Fibre Off-Axis Orientation

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TRANSAcTIONS OF THE INDIAN INSTITUTE OF METALS 2020年第4期73卷 999-1006页

作者： Patel, Manish Kumar, Jalaj Kiran, Phani S. Jayakumar, T. Kumar, Vikas Prasad, V. V. Bhanu Def Met Res Lab Hyderabad 500058 India

2.5D c/Sic ceramic matrix composite is widely used for thermal protection and hot sections of gas turbine engines. The fibre axis in these components plays a big role in its performance, under multi-axial strain conditions. In the present investigation, the effect of fibre orientations has been studied. Three-point bend specimens of this composite with 30 degrees/- 60 degrees, 45 degrees/- 45 degrees and 0 degrees/90 degrees fibre orientations have been prepared and tested under bending loads. Various mechanical parameters such as flexural strength and Young's modulus have been evaluated. A considerable reduction in the flexural strength and Young's modulus has been observed in this composite with 30 degrees/- 60 degrees and 45 degrees/- 45 degrees fibre off-axis orientations. In situ damage assessment has been conducted with the help of the acoustic emission technique. Various micro-mechanics parameters such as the matrix cracking stress, matrix cracking saturation stress and stress for fibre fracture initiation have been derived using acoustic emission data as a function of the off-axis orientation of the fibres.

关键词： c Sic ceramic matrix composite Off-axis orientation Damage assessment

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Fabrication and characterization of N-TiO2/c/ATP composite with Enhanced Visible-Light Photocatalytic Performance for the Degradation of Polyacrylamide in Wastewater

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cHEMISTRYSELEcT 2020年第17期5卷 5349-5359页

作者： Zhu, Pengfei Xie, Lisi Duan, Ming Hu, Min Xu, Jing Wang, Ruoxu Southwest Petr Univ Sch Chem & Chem Engn Chengdu 610500 Peoples R China Southwest Petr Univ Res Inst Ind Hazardous Waste Disposal & Resource Chengdu 610500 Sichuan Peoples R China Southwest Petr Univ Oil & Gas Field Appl Chem Key Lab Sichuan Prov Chengdu 610500 Peoples R China

A novel N-TiO2/c/attapulgite (N-TiO2/c/ATP) composite photocatalyst was prepared by sol-gel method using ATP supported o-phenanthroline modified TiO2. The as-prepared samples were characterized by X-ray diffraction (XRD), fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS) and N-2 adsorption-desorption measurements. The activity of these photocatalysts was tested by degrading polyacrylamide (PAM) under visible light irradiation while N-TiO2/c/ATP shows significant photocatalytic enhancement compared to pure TiO2. The optimal ratio of N-TiO2/c/ATP photocatalyst is n (TiO2): n (o-phenanthroline)=20 : 1 and the m (N-TiO2/c): m (ATP)=1 : 1. When the initial concentration of PAM is 300 mg/L and the catalyst dosage is 1.5 g/L, the removal rate of chemical oxygen demand (cOD) reaches 86.3 % at pH 2 under 2 h of visible light. The enhanced performance can be attributed to the c element in o-phenanthroline is modified on the TiO2 surface as a surface sensitizer and the N element may enter anatase TiO2 lattice and replace to form O-Ti-N bond. Meanwhile, some TiO2 particles were permeated into the layer of ATP, which made the composite photocatalyst more stable and the N-TiO2/c/ATP composite exhibits good stability after three times recycling. In addition, the possible photocatalytic mechanism is proposed at the end.

关键词： adsorption composite N-TiO2 c ATP photocatalysis polyacrylamide

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Nickel-Induced Developmental Neurotoxicity in c. elegans Includes cholinergic, Dopaminergic and GABAergic Degeneration, Altered Behaviour, and Increased SKN-1 Activity

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NEUROTOXIcITY RESEARcH 2020年第4期37卷 1018-1028页

作者： Ijomone, Omamuyovwi M. Miah, Mahfuzur R. Akingbade, Grace T. Bucinca, Hana Aschner, Michael Albert Einstein Coll Med Dept Mol Pharmacol New York NY 10461 USA Fed Univ Technol Akure Neurolab Dept Human Anat Sch Hlth & Hlth Technol Akure Nigeria Albert Einstein Coll Med Dept Neurosci New York NY 10461 USA

Nickel (Ni) is a ubiquitous metal in the environment with increasing industrial application. While environmental and occupational exposure to Ni compounds has been known to result in toxicities to several organs, including the liver, kidney, lungs, skin and gonads, neurotoxic effects have not been extensively investigated. In this present study, we investigated specific neuronal susceptibility in a c. elegans model of acute Ni neurotoxicity. Wild-type worms and worms expressing green fluorescent protein (GFP) in either cholinergic, dopaminergic or GABAergic neurons were treated with Nicl2 for 1 h at the first larval (L1) stage. The median lethal dose (LD50) was calculated to be 5.88 mM in this paradigm. Morphology studies of GFP-expressing worms showed significantly increasing degeneration of cholinergic, dopaminergic and GABAergic neurons with increasing Ni concentration. Significant functional changes in locomotion and basal slowing response assays reflected that cholinergic and dopaminergic neuronal function, respectively, were impaired due to Ni treatment. Interestingly, a small but significant number of worms exhibited shrinker phenotype upon Ni exposure but no loopy head foraging behaviour was observed suggesting that function of D-type GABAergic neurons of c elegans may be specifically attenuated while the RME subset of GABAergic neurons are not. GFP expression due to induction of glutathione S-transferase 4 (gst-4), a target of Nrf2 homolog skn-1, was increased in a Pgst-4::GFP worm highlighting Ni-induced oxidative stress. RT-qPcR verified upregulation of this expression of gst-4 immediately after exposure. These data suggest that oxidative stress is associated with neuronal damage and altered behaviour due to developmental Ni exposure.

关键词： Nickel c elegans Neurodegeneration Behaviour Oxidative stress

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Effect of carbon-to-nitrogen ratio on eco-friendly mycoherbicide activity from Lasiodiplodia pseudotheobromae c1136 for sustainable weeds management in organic agriculture

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ENVIRONMENT DEVELOPMENT AND SUSTAINABILITY 2020年第3期22卷 1977-1990页

作者： Adetunji, charles Oluwaseun Oloke, Julius Kola Prasad, Gandham Landmark Univ Dept Microbiol Appl Microbiol Biotechnol & Nanotechnol Lab Omu Aran Nigeria Ladoke Akintola Univ Technol Dept Pure & Appl Biol PMB 4000 Ogbomosho Oyo State Nigeria Inst Microbial Technol Dept Mol Biol Sect 39A Chandigarh India Inst Microbial Technol Microbial Type Culture Collect & Gene Bank MTCC Sect 39A Chandigarh India

The utilization of bioherbicides in place of chemical herbicides has been described as one of the sustainable eco-friendly technologies that can improve agricultural outputs. This work investigated the impact of different carbon and nitrogen sources on the bioherbicidal efficiency of Lasiodiplodia pseudotheobromae (c1136). The preliminary screening of various carbon and nitrogen sources was carried out, out of which sucrose and peptone were selected for further c:N ratio investigations using strain c1136. The fungus produces a different quantity of mycelium biomass and spores in varied ratios of c:N when compared to the basal medium. Also, the effect of c:N ratio was tested by evaluating for leaf necrosis assay, mortality rate and the dry-matter biomass from the aerial parts of chromolaena odoratum and Echinochloa crus-galli under guided laboratory and screen house conditions. Both the 7.5:1 and 10:1 ratios produced optimal spores count of 6.1 x 10(7) and 5.9 x 10(7) cFU/mL, respectively (p = 0.05) when compared to the control containing potatoes dextrose broth without any carbon or nitrogen amendment produced a spores count of 1.1 x 10(7) cFU/mL. Also, the phytotoxic metabolite amended with c:N of 10:1 showed a strong herbicidal, high mortality and a significant decrease in dry weight on the seedling on the tested weeds. This demonstrated hypothetically the optimization influence of carbon (sucrose)-nitrogen (peptone) manipulations either in variable combination or as single nutrient based on the cultural development of strain c1136. Spores, mycelium biomass and biocontrol efficacy of the fungus all experienced accretion in sucrose and peptone nutrient environment and likewise support their use as an attractive alternative in the optimization of mycoherbicidal assays.

关键词： Mycelium biomass Nitrogen carbon Sporulation c N ratio Mycoherbicide

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Wheat Growth-Induced changes in Phosphorus Pools in the crop Residue Detritusphere Are Influenced by Residue c/P Ratio

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JOURNAL OF SOIL ScIENcE AND PLANT NUTRITION 2020年第4期20卷 2579-2586页

作者： Erinle, Kehinde O. Marschner, Petra Univ Adelaide Sch Agr Food & Wine Adelaide SA 5005 Australia

This experiment was carried out to elucidate the effect of residue c/nutrient ratio on P pools and N availability in wheat rhizosphere. The microcosms included an upper and a lower PVc core with one end of both cores covered by nylon mesh. Wheat was planted in the upper core. To the lower core, crop residues were added as a thin uniform layer on the top mesh. Treatments were control without residue or wheat growth, wheat growth without crop residue, barley straw without or with wheat growth, and barley faba bean residue without or with wheat growth. Sampling was carried out after 14 and 28 days in wheat rhizosphere alone, detritusphere of faba bean residue and barley straw, and in the rhizosphere/detritusphere interface. Mass loss of low c/P faba bean residue was greater than of high c/P barley straw;and mass loss was greater in the detritusphere alone than in the rhizosphere/detritusphere interface. Plant P concentration and P uptake were higher with faba bean residue than with straw and unamended wheat plants. With faba bean, most P pools and N availability, but not microbial biomass N and P, were lower in the rhizosphere/detritusphere interface than detritusphere alone. P pools were higher in detritusphere of faba bean residue than wheat rhizosphere alone. With straw, P pools and MBN were low and not affected by wheat roots. P pools and N availability in the wheat rhizosphere/detritusphere interface were influenced by residue type, and plant nutrient uptake reduced P pools and available N only with low carbon/nutrient faba bean residue.

关键词： c nutrient ratio crop-litter interface P pools Rhizosphere

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LINc00160 mediated paclitaxel-And doxorubicin-resistance in breast cancer cells by regulating TFF3viatranscription factor c/EBPβ

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JOURNAL OF cELLULAR AND MOLEcULAR MEDIcINE 2020年第15期24卷 8589-8602页

作者： Wu, Huaiguo Gu, Juan Zhou, Daoping cheng, Wei Wang, Yueping Wang, Qingping Wang, Xuedong Anhui 2 Prov Peoples Hosp Ctr Precis Med Hefei Peoples R China Nanjing Med Univ Peoples Hosp Wuxi 5 Dept Med Lab Sci 1215 Guangrui Rd Wuxi 214000 Jiangsu Peoples R China Jiangnan Univ Peoples Hosp Wuxi 5 Med Sch Dept Pathol Wuxi Jiangsu Peoples R China Massachusetts Univ Coll Arts & Sci Dept Biol Boston MA USA

chemoresistance represents a major challenge in breast cancer (Bc) treatment. This study aimed to probe the roles of LINc00160 in paclitaxel- and doxorubicin-resistant Bc cells. Three pairs of Bc and adjacent normal tissue were used for lncRNA microarray analysis. Paclitaxel-resistant McF-7 (McF-7/Tax) and doxorubicin-resistant BT474 (BT474/Dox) cells were generated by exposure of parental drug-sensitive McF-7 or BT474 cells to gradient concentrations of drugs. correlation between LINc00160 expression and clinical response to paclitaxel in Bc patients was examined. Short interfering RNAs specifically targeting LINc00160 or TFF3 were designed to construct LINc00160- and TFF3-depleted Bc cells to discuss their effects on biological episodes of McF-7/Tax and BT474/Dox cells. Interactions among LINc00160, transcription factor c/EBP beta and TFF3 were identified. McF-7/Tax and BT474/Dox cells stable silencing of LINc00160 were transplanted into nude mice. consequently, up-regulated LINc00160 led to poor clinical response to paclitaxel in Bc patients. LINc00160 knockdown reduced drug resistance in McF-7/Tax and BT474/Dox cells and reduced cell migration and invasion. LINc00160 recruited c/EBP beta into the promoter region of TFF3 and increased TFF3 expression. LINc00160-depleted McF-7/Tax and BT474/Dox cells showed decreased tumour growth rates in nude mice. Overall, we identified a novel mechanism of LINc00160-mediated chemoresistance via the c/EBP beta/TFF3 axis, highlighting the potential of LINc00160 for treating Bc with chemoresistance.

关键词： breast cancer c EBP beta drug resistance long non-coding RNA-00160 TFF3

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